Non-alcoholic fatty liver disease (NAFLD) is characterized by excessive lipid accumulation in hepatocytes without significant alcohol consumption. It is closely associated with sedentarism, hypercaloric diets, obesity, dyslipidemia, insulin resistance, type 2 diabetes mellitus, and genetic predisposition. NAFLD comprises a spectrum of liver disorders, from simple steatosis to non-alcoholic (NASH) and liver cirrhosis. The complex etiological mechanisms include oxidative stress, inflammation, apoptosis, and fibrosis; therefore, its management is challenging. Sodium-glucose cotransporter type 2 inhibitors (SGLT2i), a class of antidiabetic drugs, have emerged as promising therapeutic agents due to their ability to improve key metabolic parameters, including obesity, dyslipidemia, insulin resistance, and hyperglycemia. This review explores the cellular mechanisms by which SGLT2i, either as monotherapy or combined with other treatments, modulate signaling pathways involved in lipid and carbohydrate metabolism. Additionally, we examine their effects on oxidative stress, inflammation, fibrosis, and apoptosis, which are critical drivers of NAFLD progression. This review is intended to summarize the multiple benefits of SGLT2 inhibitors and to educate healthcare providers on the therapeutic potential of these drugs in order to foster their incorporation into effective NAFLD management plans.

Obesity is characterized by an enlargement of white adipose tissue caused by caloric excess. The depot-specific adaptation of white adipose tissue in individuals resistant to obesity despite a high-calorie diet is crucial for understanding the pathogenesis of obesity and related metabolic disorders. Our aim was to characterize the metabolic and morphological state of obesity resistance and to investigate depot-specific changes in signaling pathways in epididymal visceral (eVAT) and inguinal subcutaneous (iSAT) white adipose tissue of C57BL/6J male mice on a high-fat diet (60 kcal% fats). After 14 weeks, the mice were categorized as obese (at least 30% higher body mass compared to the control group) or obesity-resistant (weight gain below 30%). Biochemical and morphological parameters, as well as histology, and signaling pathways involved in lipid metabolism, inflammation, and insulin sensitivity were investigated in eVAT and iSAT. The results showed unaltered body, total VAT and iSAT mass in obesity-resistant mice despite increased caloric intake. Leptin levels and glucose homeostasis were improved in these animals compared to the obese mice. In both eVAT and iSAT of the obesity-resistant mice, adipocyte size and lipolytic capacity were retained at control levels, while compared to the obese mice, preserved capacity for adipogenesis, improved local insulin sensitivity and the absence of inflammation were observed only in the eVAT. In conclusion, metabolic adaptation of eVAT rather than iSAT may have a substantial impact on the maintenance of the obesity-resistant phenotype with fewer metabolic complications, which could contribute to the improvement of existing obesity therapies.

De novo lipogenesis (DNL) converts excess glucose into lipids, whereas the hexosamine biosynthetic pathway (HBP), a glycolytic branch, generates UDP-N-acetylglucosamine for protein glycosylation, including O-GlcNAcylation and N-linked glycosylation. Both pathways are active in hepatocytes and integral to glucose metabolism; however, their functional interplay remains unclear. Here, we investigated the role of HBP in hepatic DNL activation using both in vitro and in vivo models. AML12 hepatocytes were cultured in low- and high-glucose media with or without HBP blockade, both pharmacologically and genetically. For in vivo studies, male C57BL/6J mice were subjected to a fasting-refeeding regimen with or without intraperitoneal administration of azaserine, a competitive inhibitor of glutamine-fructose-6-phosphate transaminase 1 (GFPT1), the rate-limiting enzyme of the HBP. Our results demonstrated that, in AML12 cells, glucose exposure activated both DNL and HBP, leading to triacylglycerol (TAG) accumulation, whereas HBP inhibition ameliorated DNL and TAG accumulation. In mice, refeeding after a 24-h fasting induced hepatic DNL, which was abolished by HBP inhibition, indicating its mechanistic involvement in glucose-driven lipogenesis. Mechanistically, we identified ATF4 as a key regulator of GFPT1 upregulation under high-glucose conditions. As expected, both glucose-treated hepatocytes and livers from fasting-refed mice exhibited increased protein glycosylation. Notably, blocking N-linked glycosylation, but not O-GlcNAcylation, abolished glucose-induced DNL activation, indicating that HBP is essential for glucose-induced DNL pathway activation via promoting N-linked glycosylation, independent of O-GlcNAcylation. In conclusion, our findings establish that an intact HBP is required for glucose-induced hepatic DNL activation, primarily through promoting protein N-linked glycosylation.NEW & NOTEWORTHY High-glucose exposure activates both hepatic HBP and DNL pathways. The glucose metabolism into HBP is essential for the activation of the DNL pathway. ATF4 activation plays a mechanistic role in high glucose-induced HBP activation. HBP drives high glucose-induced hepatic DNL activation via promoting N-linked protein glycosylation.

Insulin-like growth factor 1 (IGF1) is a regulator of both cellular hypertrophy and lipogenesis, which are two key processes for pathogenesis of obesity. However, the in vivo role of IGF1 in the development of obesity remains unclear. Here, we show that IGF1 expression is increased in adipose tissue in obese human patients and animal models. Elevation of IGF1 is associated with increased lipogenic gene expression and decreased energy expenditure. Genetic down-regulation of IGF1 normalizes lipogenic gene expression, restores aberrant energy metabolism and alleviates obese phenotype of a genetic mouse model with IGF1-hypersecretion. Importantly, genetic down-regulation of IGF1 exerts similar effects on development of diet-induced obesity. Furthermore, berberine that is an AMP-activated protein kinase (AMPK) activator in medicinal herbs inhibits IGF1 secretion, decreases lipogenic gene expression and alleviates diet-induced adiposity. Collectively, our findings demonstrate that hypersecretion of IGF1 is a critical factor for the development of obesity and can be targeted using AMPK activators to alleviate obesity.

Ubiquitin-specific peptidase 24 (USP24), a deubiquitinating enzyme, regulates protein stability by removing ubiquitin. This study investigates the role of UPS24 in lipid metabolism, inflammation, and fibrosis. It also explores the effect of targeting USP24 on metabolic disorders, focusing on high-fat diet (HFD)-induced obesity and liver diseases.

This study utilized CRISPR/Cas9 to create functional knockout mice (USP24C1695A) and treated HFD-fed mice with USP24 inhibitor (USP24-i-101). The effects of USP24 inhibition or knockout on 3T3-L1 derived adipocytes, primary hepatocytes, hepatic stellate cells, and murine hepatocyte cell line AML12 (alpha mouse liver 12) cells were assessed with RNA-sequencing. Molecular mechanisms and the interaction between USP24 and PKA-Cα were studied with co-immunoprecipitation. Downstream signaling pathways involving CREB, SREBP1, PPARγ, and C/EBPβ, as well as USP24 role in liver inflammation and fibrosis, were studied using western blot and real-time PCR. Clinical and animal tissue samples were examined with immunohistochemistry to identify the correlations between USP24 and metabolic-associated liver diseases.

Knockout or inhibition of USP24 reduced body weight, lipid accumulation, inflammation, and fibrosis in HFD-fed mice. The expression of genes related to lipogenesis, inflammation, and fibrosis was downregulated in USP24C1695A mice and those treated with USP24 inhibitor (USP24-i-101). USP24 inhibition decreased lipid droplet accumulation in adipocytes and hepatocytes, suppressed inflammation in hepatocytes and AML12 cells, and reduced fibrosis in hepatic stellate cells. Mechanistically, USP24 expression was upregulated by PKA activation during adipocyte differentiation, leading to increased PKA-Cα stability and CREB phosphorylation, which promoted lipogenic gene expression. Free fatty acids (FFA) increased USP24 expression, activating NF-κB and TGFβ pathways to induce inflammation (Cox2) and fibrosis (α-SMA). USP24 was highly expressed in patients with metabolic dysfunction-associated steatohepatitis (MASH) and correlated with Cox2 and α-SMA levels.

Citrus aurantium L. var. amara Engl. is a folk medicine and dietary supplement popularly used in alleviating indigestion due to food retention and obesity. p-Synephrine, a principal proto-alkaloid in Citrus aurantium L. var. amara Engl., is extensively utilized due to its numerous benefits, particularly its potential to ameliorate obesity. Previous studies of our research demonstrated that p-synephrine had the potential to alleviate insulin resistance (IR) and liver lipid accumulation caused by high-fat diet (HFD), as well as enlargement of cells in adipose tissue. However, the effects of p-synephrine in ameliorating non-alcoholic fatty liver disease (NAFLD) were still unclear.

To explore the effects of p-synephrine on HFD-induced NAFLD and its mechanisms.

NAFLD mice were developed by HFD feeding and treated with p-synephrine once a day for 21 weeks. The protective effects of p-synephrine against NAFLD and its mechanisms were evaluated by OGTT, ITT, biochemical index measurements, H&E, immunofluorescence, Sirius red staining, oil red O staining, immunohistochemistry, RT-qPCR, Western blot, network pharmacology, and molecular docking assays.

The results of network pharmacology suggested that AMPK-α1 might be the core target, and AMPK and insulin signaling pathways might be the key regulatory pathways of p-synephrine to alleviate NAFLD. Molecular docking confirmed AMPK-α1 as a probable direct molecular target. p-Synephrine significantly reduced HFD-induced weight gain of the body, liver, and iWAT. It improved glucose tolerance, insulin tolerance and lipid metabolism disorders caused by HFD. Serum levels of NO, TNF-α, and IL-6 in NAFLD mice were suppressed. AST, ALT, and HYP levels in serum and liver were inhibited. Morphological observation showed p-synephrine alleviated hepatic steatosis and fibrosis. p-Synephrine administration also significantly inhibited hepatic de novo lipogenesis (DNL), as evidenced by its regulation of non-esterified fatty acid (NEFA) and TG contents, as well as SREBP-1c, FASN, and ACC1 mRNA expression levels. p-Synephrine also reversed HFD-induced histopathological changes in iWAT, promoted iWAT browning by increasing UCP1 and PGC-1α expression. Simultaneously, p-synephrine intervention markedly increased phosphorylation levels of IRS-1, PI3K, and Akt, and protein expression of GLUT-4 in iWAT and liver. Expression of TNF-α, IL-6, and IL-1β and NF-κB activation in iWAT and liver were attenuated through the treatment of p-synephrine. Further assays showed that p-synephrine intervention potently regulated AMPK pathway in iWAT and liver of mice.

This investigation proposed that p-synephrine had the potential to ameliorate HFD-induced NAFLD by regulating liver-adipose axis through AMPK/NF-κB pathway.

De novo lipogenesis is associated with the development of human diseases such as cancer, diabetes, and obesity. At the core of lipogenesis lies acetyl coenzyme A (CoA), a metabolite that plays a crucial role in fatty acid synthesis. One of the pathways contributing to the production of cytosolic acetyl-CoA is mediated by acetyl-CoA synthetase 2 (ACSS2). Here, we reveal that when cells encounter nutrient stress, particularly a deficiency in amino acids, Sirtuin 2 (SIRT2) catalyzes the deacetylation of ACSS2 at the lysine residue K271. This results in K271 ubiquitination and subsequently proteasomal degradation of ACSS2. Substitution of K271 leads to decreased ubiquitination of ACSS2, increased ACSS2 protein level, and thus increased lipogenesis. Our study uncovers a mechanism that cells employ to efficiently manage lipogenesis during periods of nutrient stress.

This study aimed to explore the effects of chili meal (CM), a by-product of chili pepper oil extraction, on the productive performance, intestinal health, and lipid metabolism of laying hens fed low-protein (LP) diets. A total of 384 Hy-Line brown laying hens (32 weeks old) were divided into six groups: control (CON) diet with 16.5 % crude protein (CP), LP diet with 15 % CP, and LP diets supplemented with 3 %, 5 %, 7 %, and 9 % CM. Results showed that dietary CM supplementation of up to 5 % did not negatively affect the productive performance of laying hens fed LP diets. However, the groups receiving 7 % and 9 % CM exhibited a significant increase in the feed-to-egg ratio (P < 0.05). Additionally, dietary CM supplementation effectively enhanced egg yolk color in a dose-dependent manner (P < 0.05). Intestinal morphology analysis indicated that the 5 % CM group had a higher villus height-to-crypt depth ratio than the LP and 9 % CM groups (P < 0.05), with no significant differences among the other groups. Dietary supplementation with 3 %-7 % CM did not significantly affect serum and jejunal antioxidant capacity, and the 9 % CM group exhibited the highest levels of serum and jejunal malondialdehyde among the groups (P < 0.05). Dietary CM supplementation significantly increased anti-inflammatory cytokines (IL-4 and IL-10) and decreased pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α) in the serum and jejunal tissue of laying hens (P < 0.05). Moreover, CM supplementation significantly altered the cecal microbiota composition in laying hens, increasing the abundance of beneficial bacteria, such as Desulfovibrio and Megamonas. Furthermore, dietary CM supplementation significantly decreased serum triglyceride levels; downregulated liver mRNA levels of ACC, FAS, and SREBP-1C/2; and upregulated the mRNA levels of ACOX1, PPAR-α, Apob, and CPT in laying hens fed LP diets. In conclusion, CM supplementation should not exceed 5 % to avoid negative impacts on performance while supporting intestinal health and lipid metabolism.

Adipose tissue exhibits remarkable plasticity in adapting to thermal stress, yet the epigenetic mechanisms coordinating metabolic reprogramming in large mammals-particularly in livestock species lacking classical brown adipose tissue (BAT) such as swine-remain elusive. Using a porcine cold exposure model, we investigated adipose adaptation mechanisms through integrated single-cell RNA sequencing and bulk transcriptomic analyses of subcutaneous adipose tissue (subWAT). We identified a cold-induced thermogenic adipocyte subpopulation, characterized by upregulated DHRS4 expression. Mechanistically, cold exposure induced hypomethylation at the DHRS4 promoter locus, enhancing its expression to potentiate fatty acid β-oxidation, accompanied by thermogenic capacity upregulation. Our findings establish DHRS4 as an epigenetic-metabolic switch governing cold adaptation and a potential target for improving cold resistance in swine production systems.

Recent research has highlighted the complex relationship between gut microbiota, metabolic pathways, and nonalcoholic fatty liver disease (NAFLD) progression. Gut dysbiosis, commonly observed in NAFLD patients, impairs intestinal permeability, leading to the translocation of bacterial products like lipopolysaccharides, short-chain fatty acids, and ethanol to the liver. These microbiome-associated mechanisms contribute to intestinal and hepatic inflammation, potentially advancing NAFLD to NASH. Dietary habits, particularly those rich in saturated fats and fructose, can modify the microbiome composition, leading to dysbiosis and fatty liver development. Metabolomic approaches have identified unique profiles in NASH patients, with specific metabolites like ethanol linked to disease progression. While bariatric surgery has shown promise in preventing NAFLD progression, the role of gut microbiome and metabolites in this improvement remains to be proven. Understanding these microbiome-related pathways may provide new diagnostic and therapeutic targets for NAFLD and NASH. A comprehensive review of current literature was conducted using multiple medical research databases, including PubMed, Scopus, Web of Science, Embase, Cochrane Library, ClinicalTrials.gov, ScienceDirect, Medline, ProQuest, and Google Scholar. The review focused on studies that examine the relationship between gut microbiota composition, metabolic pathways, and NAFLD progression. Key areas of interest included microbial dysbiosis, endotoxin production, and the influence of diet on gut microbiota. The analysis revealed that gut dysbiosis contributes to NAFLD through several mechanisms, diet significantly influences gut microbiota composition, which in turn affects liver function through the gut-liver axis. High-fat diets can lead to dysbiosis, altering microbial metabolic activities and promoting liver inflammation. Specifically, gut microbiota-mediated generation of saturated fatty acids, such as palmitic acid, can activate liver macrophages and increase TNF-α expression, contributing to NASH development. Different dietary components, including cholesterol, fiber, fat, and carbohydrates, can modulate the gut microbiome and influence NAFLD progression. This gut-liver axis plays a crucial role in maintaining immune homeostasis, with the liver responding to gut-derived bacteria by activating innate and adaptive immune responses. Microbial metabolites, such as bile acids, tryptophan catabolites, and branched-chain amino acids, regulate adipose tissue and intestinal homeostasis, contributing to NASH pathogenesis. Additionally, the microbiome of NASH patients shows an elevated capacity for alcohol production, suggesting similarities between alcoholic steatohepatitis and NASH. These findings indicate that targeting the gut microbiota may be a promising approach for NASH treatment and prevention. Recent research highlights the potential of targeting gut microbiota for managing nonalcoholic fatty liver disease (NAFLD). The gut-liver axis plays a crucial role in NAFLD pathophysiology, with dysbiosis contributing to disease progression. Various therapeutic approaches aimed at modulating gut microbiota have shown promise, including probiotics, prebiotics, synbiotics, fecal microbiota transplantation, and dietary interventions. Probiotics have demonstrated efficacy in human randomized controlled trials, while other interventions require further investigation in clinical settings. These microbiota-targeted therapies may improve NAFLD outcomes through multiple mechanisms, such as reducing inflammation and enhancing metabolic function. Although lifestyle modifications remain the primary recommendation for NAFLD management, microbiota-focused interventions offer a promising alternative for patients struggling to achieve weight loss targets.

Non-alcoholic fatty liver disease (NAFLD) is a common comorbidity in type 2 diabetes mellitus (T2DM), with shared pathophysiological mechanisms, including insulin resistance, oxidative stress, and inflammation.

This study evaluates the effects of vitamin E and ertugliflozin, individually and in combination, alongside standard pioglitazone therapy, on hepatic and metabolic parameters in patients with NAFLD and T2DM.

A 24-week, double-blind, randomized, controlled clinical trial on 173 patients with NAFLD and T2DM was assigned into four groups: vitamin E (n = 42), pioglitazone (n = 43), ertugliflozin (n = 44), and vitamin E + ertugliflozin (n = 44) combination therapy. The primary outcome was to monitor changes in liver steatosis assessed via ultrasound. Secondary outcomes included evaluation of liver enzymes, glycemic control, fibrosis markers, and lipid profiles.

Combination therapy of vitamin E + ertugliflozin showed the highest decrease in liver fat content, with 11 participants achieving successful Grade 0 (p < 0.001). Significant improvements were also observed in glycemic control, HbA1c, triglycerides, and liver enzymes. Ertugliflozin monotherapy showed significant efficacy in improving liver enzymes, glycemic parameters, and fibrosis markers. Pioglitazone improved the initial stage of NAFLD but had a limited impact on advanced fibrosis. Ertugliflozin, in combination with vitamin E, decreases oxidative stress; however, vitamin E by itself has no impact on the metabolic and fibrosis index.

The ertugliflozin and vitamin E combination is a very effective treatment for patients with NAFLD and T2DM. It improves hepatic steatosis and metabolic indicators. Exploration is required for combination therapy in order to assess the prolonged efficacy and safety of the treatment.

Hepatocellular Carcinoma (HCC), a highly prevalent malignancy, poses a significant global health challenge. Its pathogenesis is intricate and multifactorial, involving a complex interplay of environmental and genetic factors. Viral hepatitis, excessive alcohol consumption, and cirrhosis are known to significantly elevate the risk of developing HCC. The underlying biological processes driving HCC are equally complex, encompassing aberrant activation of molecular signaling pathways, dysregulation of hepatocellular differentiation and angiogenesis, and immune dysfunction. This review delves into the multifaceted nature of HCC, exploring its etiology and the intricate molecular signaling pathways involved in its development. We examine the role of immune dysregulation in HCC progression and discuss the potential of emerging therapeutic strategies, including immune-targeted therapy and tumor-associated macrophage interventions. Additionally, we explore the potential of traditional Chinese medicine (TCM) monomers in inhibiting tumor growth. By elucidating the complex interplay of factors contributing to HCC, this review aims to provide a comprehensive understanding of the disease and highlight promising avenues for future research and therapeutic development.

The combination of a tunable quantum cascade laser (QCL) and plasmonic mid-infrared (MIR) metasurface is a powerful tool enabling label-free high-content microscopy of hydrated cells using the vibrational contrast of their constituent biomolecules. While the QCL provides a high-brightness source whose frequency can be rapidly tuned to that of the relevant molecular vibration, the metasurface is used to overcome water absorption of MIR light. Here we employ the resulting Metasurface-enabled Inverted Reflected-light Infrared Absorption Microscopy (MIRIAM) tool for non-destructive monitoring of the vital process of de novo lipogenesis (DNL), by which fat tissue cells (adipocytes) synthesize fatty acids from glucose and store them inside lipid droplets. Using 13 C-labeled glucose as a metabolic probe, we produce spatially- and temporally-resolved images of 13 C incorporation into lipids and proteins, observed as red-shifted vibrational peaks in the MIR spectra. These findings demonstrate MIRIAM's capability for studying metabolic pathways with molecular specificity, offering a powerful platform for label-free imaging of cellular metabolism.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common chronic liver disease worldwide, with a prevalence as high as 32.4%. MASLD encompasses a spectrum of liver pathologies, ranging from steatosis to metabolic dysfunction-associated steatohepatitis (MASH), fibrosis, and, in some cases, progression to end-stage liver disease (cirrhosis and hepatocellular carcinoma). A comprehensive understanding of the pathogenesis of this highly prevalent liver disease may facilitate the identification of novel targets for the development of improved therapies. E3 ubiquitin ligases and deubiquitinases (DUBs) are key regulatory components of the ubiquitin‒proteasome system (UPS), which plays a pivotal role in maintaining intracellular protein homeostasis. Emerging evidence implicates that aberrant expression of E3 ligases and DUBs is involved in the progression of MASLD. Here, we review abnormalities in E3 ligases and DUBs by (1) discussing their targets, mechanisms, and functions in MASLD; (2) summarizing pharmacological interventions targeting these enzymes in preclinical and clinical studies; and (3) addressing challenges and future therapeutic strategies. This review synthesizes current evidence to highlight the development of novel therapeutic strategies based on the UPS for MASLD and progressive liver disease.

Adipose tissue is essential for maintaining glucose and lipid homeostasis in mammals. The histone chaperone HIRA has been reported to play a lineage- and stage-selective role during development. However, its role in adipose tissue development and function as well as its working mechanism remain unknown. Here we show that tissue-specific knockout of histone chaperone HIRA in mice impairs insulin sensitivity and alleviates adipose tissue expansion during high-fat diet-induced obesity, but only moderately affects embryonic development of adipose tissue. Mechanistically, HIRA is selectively required for expression of genes critical for insulin response and lipogenesis, rather than adipogenesis, in adipose tissue. By acute depletion of HIRA protein and by mapping HIRA genomic localization in adipocytes, we demonstrate that HIRA binds to promoters and enhancers of insulin response and lipogenesis genes and regulates their expression by facilitating transcription elongation. Our findings not only identify HIRA as an epigenomic regulator of insulin sensitivity, lipogenesis, and obesity-associated adipose expansion, but also reveal a novel mechanism by which HIRA regulates transcription.

Aquafeed formulation has progressively reduced its dependence on fish-derived ingredients over the past decades. Plant-based substitutes have been a major focus, with soybean meal and its derivatives leading the way. However, many plants contain phytoestrogens, which may affect fish physiology. This study aimed to assess in vitro the effects of genistein (GE), daidzein (DZN), glycitein (GLY), and coumestrol (COU) on the lipid metabolism of rainbow trout (Oncorhynchus mykiss) and gilthead sea bream (Sparus aurata). Primary cultured adipocytes were incubated with these phytoestrogens, along with 17β-estradiol, at two doses each (1, 10, or 100 μM). The 100 μM dose of GE and DZN decreased adipocyte viability, and mainly enhanced lipid accumulation in both species, suggesting a hypertrophic condition. However, the reduction in adipocyte number and lipid content with 100 μM DZN in rainbow trout indicated a limiting effect on adipose tissue growth in this species. Interestingly, COU significantly increased cell viability in gilthead sea bream, potentially leading to hyperplastic growth, a more favorable metabolic state. In that species, which proved to be more phytoestrogens-sensitive, lipoprotein lipase was generally downregulated upon treatments. Moreover, 10 µM GE significantly decreased the mRNA levels of fatty acid transport protein 1 and fatty acid synthase, and increased those of fatty acid binding protein 1, suggesting an acceleration of the differentiation process compared to the control cells. This work provides new insights into how dietary phytoestrogens modulate fish lipid metabolism and supports that their presence in plant protein feedstuffs can potentially affect fish health and production performance.

Visceral adipose tissue (VAT) plays a crucial role in regulating systemic metabolic balance. Excess accumulation of VAT is closely associated with various metabolic disorders, a process that involves the coordinated actions of multiple cell types within the tissue. Cold exposure, as a potential intervention, has been proposed to improve metabolic dysfunction. However, the heterogeneity of VAT and its comprehensive metabolic characteristics under cold exposure remain unclear.

We collected epididymal white adipose tissue (eWAT) of C57BL/6J mice after cold exposure at three different time points for single-nucleus RNA sequencing (snRNA-seq) analysis.

We successfully identified ten major cell types in eWAT, enabling understanding of the dynamic changes in the eWAT microenvironment and its metabolic features during cold exposure. This study revealed that cold exposure for 1 day reduced cellular metabolic activity and intercellular communication in eWAT including receptor-ligand-based cell communication and metabolite-mediated interactions. However, after 14 days of cold acclimation, the metabolic activity of adipocytes was significantly enhanced, and intercellular metabolic communication was restored. Additionally, prolonged cold exposure promoted the formation of a distinct adipocyte subpopulation that may be associated with UCP1-independent thermogenesis. These changes may be a new homeostatic state established by VAT to adapt to the cold environment. The study also identified the importance of adipocytes, adipose stem and progenitor cells, myeloid cells, and endothelial cells in the process of cold adaptation.

This research provides valuable insights into the cellular heterogeneity, adipocyte remodeling, and metabolic reprogramming in eWAT after cold exposure. It highlights the critical role of transcriptional dynamics in eWAT during cold exposure and provides new perspectives on the prevention and treatment of metabolic diseases.

Periodontitis is recognized as one of the most prevalent oral dysbiotic inflammatory diseases, ultimately leading to the irreversible destruction of periodontal tissues. Macrophages play a pivotal role in the development and progression of periodontitis, and the feasibility of targeting them therapeutically has been established. Since metabolic switching significantly contributes to macrophage regulation, conducting an in-depth review of macrophage metabolism in periodontitis may serve as the foundation for developing innovative treatments.

This paper has been carefully reviewed to provide a comprehensive overview of the roles played by macrophages in periodontitis and associated comorbidities. Initially, detailed presentations on the metabolic reprogramming of macrophages, including glucose, lipid, and amino acid metabolism, were provided. Subsequently, dominating macrophage phenotype and metabolism under lipopolysaccharide (LPS) stimulation or during periodontitis were presented with emphasize on critical molecules involved. Furthermore, in recognition of the close association between periodontitis and several comorbidities, the interaction among macrophage metabolism, periodontitis, and related metabolic diseases, was thoroughly discussed.

Through the examination of current research on macrophage metabolic reprogramming induced by periodontitis, this review provides potential immunometabolic therapeutic targets for the future and raises many important, yet unstudied, subjects for follow-up.

Periodontitis is recognized as one of the most prevalent oral dysbiotic inflammatory diseases, ultimately leading to the irreversible destruction of periodontal tissues. Macrophages play a pivotal role in the development and progression of periodontitis, and the feasibility of targeting them therapeutically has been established. Since metabolic switching significantly contributes to macrophage regulation, conducting an in-depth review of macrophage metabolism in periodontitis may serve as the foundation for developing innovative treatments.

This paper has been carefully reviewed to provide a comprehensive overview of the roles played by macrophages in periodontitis and associated comorbidities. Initially, detailed presentations on the metabolic reprogramming of macrophages, including glucose, lipid, and amino acid metabolism, were provided. Subsequently, dominating macrophage phenotype and metabolism under lipopolysaccharide (LPS) stimulation or during periodontitis were presented with emphasize on critical molecules involved. Furthermore, in recognition of the close association between periodontitis and several comorbidities, the interaction among macrophage metabolism, periodontitis, and related metabolic diseases, was thoroughly discussed.

Through the examination of current research on macrophage metabolic reprogramming induced by periodontitis, this review provides potential immunometabolic therapeutic targets for the future and raises many important, yet unstudied, subjects for follow-up.

Understanding the physiology and molecular mechanisms of lactogenesis is crucial for enhancing mammalian milk production. Yes-associated protein 1 (YAP1) regulated mammary epithelial cell survival during pregnancy, but its role in lactation maintenance remains unclear. We found that YAP1 was highly expressed in mammary gland across specie, with elevated expression levels during murine gestation and lactation, particularly localized in alveoli epithelial cells. In vivo administration of a YAP1 inhibitor impaired murine milk yield, mammary gland weight, alveolar structure, and mammary epithelial cell dynamics. In vitro, YAP1 positively affected mammary epithelial cell growth and the synthesis of triglyceride and α-casein. Notably, the primary lactogenesis hormone Prolactin induced cell growth and triglyceride secretion while enhancing YAP1 expression and activity. In contrast, Melatonin inhibited cell growth and triglyceride synthesis, decreasing YAP1 expression and activity. YAP1 knockdown compromised prolactin induced effects, whereas YAP1 overexpression partially rescued cell functions inhibited by melatonin. Finally, Bioinformatics analyses revealed that YAP1 regulated multiple biological processes related to lactogenesis, including cell cycle, apoptosis, endoplasmic reticulum, amino acid transport and biosynthesis, etc. These finding indicated that YAP1 is essential for mammary epithelial cells growth and secretion and played an essential role in the lactating endocrine network by mediating key hormone functions.

Overfeeding animals beyond what they eat ad libitum causes rapid adipose tissue expansion, leading to an unusual form of obesity characterized by low immune cell accumulation in fat and sustained anorexia. To investigate how overfeeding affects adipose tissue, we studied the protein secretome of fat from equally obese overfed and ad libitum-fed mice. Fat from overfed animals secretes lower amounts of immune regulatory proteins. Unexpectedly, fat from overfed mice releases larger amounts of mitochondrial proteins. Microscopy identified mitochondria in the conditioned medium of cultured fat that were found not within extracellular vesicles but rather as free extracellular organelles. The protein profile of released mitochondria was distinct from the mitochondrial protein profile of the whole fat, suggesting that the metabolic stress of overfeeding leads to the release of a mitochondrial subset favoring de novo lipogenesis. These findings add to growing evidence that cells alter their energy profiles through the release of mitochondria.

De novo lipogenesis (DNL) is a metabolic pathway that converts carbohydrates into fatty acids, primarily occurring in the liver and, to a lesser extent, in adipose tissue. While hepatic DNL is highly responsive to dietary carbohydrate intake and regulated by insulin via transcription factors like SREBP-1c, adipose DNL is more modest and less sensitive to dietary overfeeding. Dysregulated DNL contributes to metabolic disorders, including metabolic dysfunction-associated steatotic liver disease (MASLD). Lifestyle interventions, such as physical exercise, ketogenic diets, and time-restricted eating (TRE) offer promising strategies to regulate DNL and improve metabolic health. Physical exercise enhances glucose uptake in muscles, reduces insulin levels, and promotes lipid oxidation, thereby suppressing hepatic DNL. Endurance and resistance training also improve mitochondrial function, further mitigating hepatic triglyceride accumulation. Ketogenic diets shift energy metabolism toward fatty acid oxidation and ketogenesis, lower insulin, and directly downregulate lipogenic enzyme activity in the liver. TRE aligns feeding with circadian rhythms by optimizing AMP-activated protein kinase (AMPK) activation during fasting periods, which suppresses DNL and enhances lipid metabolism. The combined effects of these interventions demonstrate significant potential for improving lipid profiles, reducing hepatic triglycerides, and preventing lipotoxicity. By addressing the distinct roles of the liver and adipose DNL, these strategies target systemic and localized lipid metabolism dysregulation. Although further research is needed to fully understand their long-term impact, these findings highlight the transformative potential of integrating these approaches into clinical practice to manage metabolic disorders and their associated complications.

The interplay between oxidative stress and adipogenesis is a critical factor in the development of obesity and its associated metabolic disorders. Excessive reactive oxygen species (ROS) disrupt key transcription factors such as peroxisome proliferator-activated receptor gamma (PPARγ) and CCAAT/enhancer-binding protein alpha (C/EBPα), impairing lipid metabolism, promoting adipocyte dysfunction, and exacerbating inflammation and insulin resistance. Antioxidants, classified as endogenous (e.g., glutathione, superoxide dismutase, and catalase) and exogenous (e.g., polyphenols, flavonoids, and vitamins C and E), are pivotal in mitigating these effects by restoring redox balance and preserving adipocyte functionality. Endogenous antioxidants neutralize ROS and safeguard cellular structures; however, under heightened oxidative stress, these defenses are often insufficient, necessitating dietary supplementation. Exogenous antioxidants derived from plant-based sources, such as polyphenols and vitamins, act through direct ROS scavenging, upregulation of endogenous antioxidant enzymes, and modulation of key signaling pathways like nuclear factor kappa B (NF-κB) and PPARγ, reducing lipid peroxidation, inflammation, and adipocyte dysfunction. Furthermore, they influence epigenetic regulation and transcriptional networks to restore adipocyte differentiation and limit lipid accumulation. Antioxidant-rich diets, including the Mediterranean diet, are strongly associated with improved metabolic health, reduced obesity rates, and enhanced insulin sensitivity. Advances in personalized antioxidant therapies, guided by biomarkers of oxidative stress and supported by novel delivery systems, present promising avenues for optimizing therapeutic interventions. This review, "Crosstalk Between Antioxidants and Adipogenesis: Mechanistic Pathways and Their Role in Metabolic Health", highlights the mechanistic pathways by which antioxidants regulate oxidative stress and adipogenesis to enhance metabolic health.

Carbohydrates can be converted into fatty acids via de novo lipogenesis (DNL). Although DNL is considered inefficient, these endogenous fatty acids contribute substantially to the esterification pathway in adipose tissue, together with fatty acids of feeding. This article revisited the concepts of DNL and aimed to discuss the clinical magnitude of carbohydrate overfeeding and fat mass accumulation. Although fat storage resulting from fat intake is more favorable for fat mass accrual than carbohydrates due to molecule structure and metabolism (e.g., oxidation and thermic effect), carbohydrates can substantially participate in lipogenesis and esterification under excess carbohydrate intake over time. Regarding only monosaccharide overfeeding, glucose and fructose favor the subcutaneous and visceral adipose tissue, respectively. While fructose and sucrose are considered villains in nonalcoholic fatty liver disease, energy surplus from carbohydrates, regardless of sources, can be considered an underlying cause of obesity. Interestingly, some degree of DNL in adipocytes may be favorable to mitigate a high deposition of fatty acids in the liver, conferring a physiological role. Although "fat burns in the flame of carbohydrate" is a praiseworthy phrase that has helped describe basic concepts in biochemistry for many decades, it appears to be overvalued and extrapolated even nowadays. DNL cannot be neglected. It is time to consider DNL an efficient biochemical process in health and disease.

Idiopathic pulmonary fibrosis is a progressive and lethal interstitial lung disease with an unclear etiology and limited treatment options. Fatty acid synthase (FASN) plays various roles in metabolic-related diseases. This study demonstrates that FASN expression is increased in fibroblasts from the lung tissues of patients with idiopathic pulmonary fibrosis and in bleomycin-treated mice. In MRC-5 cells, the inhibition of FASN using shRNA or the pharmacological inhibitor C75 resulted in the increased mRNA and protein expression of glycogen synthase kinase 3β and Axin1, both negative regulators of the Wnt/β-catenin signaling pathway, and promoted autophagy. This outcome led to a decrease in β-catenin protein and mRNA levels, effectively inhibiting the proliferation, migration, and differentiation of lung fibroblasts into myofibroblasts, while inducing the differentiation of fibroblasts into adipofibroblasts. In vivo experiments showed that C75 alleviated bleomycin-induced lung fibrosis in mice by inhibiting β-catenin. In conclusion, these findings suggest that inhibiting FASN in fibroblasts may diminish the activity of the Wnt/β-catenin signaling pathway, providing a potential therapeutic avenue for pulmonary fibrosis.

Evolutionary perspectives have yielded profound insights in health and medical sciences. A fundamental recognition is that modern diet and lifestyle practices are mismatched with the human physiological constitution, shaped over eons in response to environmental selective pressures. This Darwinian angle can help illuminate and resolve issues in nutrition, including the contentious issue of fat consumption. In the present paper, the intake of saturated fat in ancestral and contemporary dietary settings is discussed. It is shown that while saturated fatty acids have been consumed by human ancestors across time and space, they do not feature dominantly in the diets of hunter-gatherers or projected nutritional inputs of genetic accommodation. A higher intake of high-fat dairy and meat products produces a divergent fatty acid profile that can increase the risk of cardiovascular and inflammatory disease and decrease the overall satiating-, antioxidant-, and nutrient capacity of the diet. By prioritizing fiber-rich and micronutrient-dense foods, as well as items with a higher proportion of unsaturated fatty acids, and in particular the long-chain polyunsaturated omega-3 fatty acids, a nutritional profile that is better aligned with that of wild and natural diets is achieved. This would help prevent the burdening diseases of civilization, including heart disease, cancer, and neurodegenerative conditions. Saturated fat is a natural part of a balanced diet; however, caution is warranted in a food environment that differs markedly from the one to which we are adapted.

The term metabolic dysfunction-associated steatotic liver disease (MASLD) refers to a group of progressive steatotic liver conditions that include metabolic dysfunction-associated steatohepatitis (MASH), which has varying degrees of liver fibrosis and may advance to cirrhosis, and independent hepatic steatosis. MASLD has a complex underlying mechanism, with patients exhibiting diverse causes and phases of the disease. India has a pool prevalence of MASLD of 38.6% in adults. In 2023, the term NAFLD has been redefined and changed to MASLD. Currently, there are no drugs approved by the FDA for the treatment of MASLD. This study investigates the potential of bioactive phytoconstituents present in spices as a therapeutic approach for MASLD. Moreover, it offers comprehensive data on several pre-clinical studies of bioactive phytoconstituents derived from spices that primarily focus on treating obesity-associated MASLD.

Spices include a high amount of bioactive chemicals and several research have indicated their diverse pharmacological activities. Bioactive phytoconstituents from common Indian spices like cinnamic acid, eugenol, curcumin, allicin, 6-gingerols, capsaicin, piperine, eucalyptol, trigonelline, and linalool have been reported to exhibit anti-MASLD effects both in-vivo and in-vitro. Bioactive phytoconstituents from different culinary species of India have shown promising potential against MASLD in pre-clinical status. Further clinical studies on a large scale would be beneficial for paving the path to the development of a new drug which is the need of time.

Previously, our metabolomic, transcriptomic, and genomic studies characterized the ceramide/sphingomyelin pathway as a therapeutic target in Alzheimer's disease, and we demonstrated that FTY720, a sphingosine-1-phospahate receptor modulator approved for treatment of multiple sclerosis, recovers synaptic plasticity and memory in APP/PS1 mice. To further investigate how FTY720 rescues the pathology, we performed metabolomic analysis in brain, plasma, and liver of trained APP/PS1 and wild-type mice. APP/PS1 mice showed area-specific brain disturbances in polyamines, phospholipids, and sphingolipids. Most changes were completely or partially normalized in FTY720-treated subjects, indicating rebalancing the "sphingolipid rheostat", reactivating phosphatidylethanolamine synthesis via mitochondrial phosphatidylserine decarboxylase pathway, and normalizing polyamine levels that support mitochondrial activity. Synaptic plasticity and memory were rescued, with spermidine synthesis in temporal cortex best corresponding to hippocampal CA3-CA1 plasticity normalization. FTY720 effects, also reflected in other pathways, are consistent with promotion of mitochondrial function, synaptic plasticity, and anti-inflammatory environment, while reducing pro-apoptotic and pro-inflammatory signals.

The mechanisms underlying obesity-induced insulin resistance remain incompletely understood, as impaired cellular insulin signaling, traditionally considered the primary driver of insulin resistance, does not always accompany impaired insulin action. Overnutrition rapidly increases plasma norepinephrine (NE), suggesting overactivation of the sympathetic nervous system (SNS). However, the role of the SNS in obesity is controversial, as both increased and decreased SNS activity (SNA) have been reported. Here, we show that reducing catecholamine (CA) release from the SNS protects against overnutrition-induced insulin resistance as well as hyperglucagonemia, adipose tissue dysfunction, and fatty liver disease, as we demonstrate utilizing a mouse model of inducible and peripherally restricted deletion of tyrosine hydroxylase (th; THΔper). A key mechanism through which heightened SNA induces insulin resistance is by triggering adipose tissue lipolysis. Increased SNA emerges as a critical driver in the pathogenesis of overnutrition-induced insulin resistance and metabolic disease independent of cellular insulin signaling.

AMP-activated protein kinase (AMPK) activators have garnered significant attention for their potential to prevent the progression of metabolic dysfunction-associated steatotic liver disease (MASLD) into liver fibrosis and to fundamentally improve liver function. The broad spectrum of pathways regulated by AMPK activators makes them promising alternatives to conventional liver replacement therapies and the limited pharmacological treatments currently available. In this study, we aim to illustrate the newly detailed multiple mechanisms of MASLD progression based on the multiple-hit hypothesis. This model posits that impaired lipid metabolism, combined with insulin resistance and metabolic imbalance, initiates inflammatory cascades, gut dysbiosis, and the accumulation of toxic metabolites, ultimately promoting fibrosis and accelerating MASLD progression to irreversible hepatocellular carcinoma (HCC). AMPK plays a multifaceted protective role against these pathological conditions by regulating several key downstream signaling pathways. It regulates biological effectors critical to metabolic and inflammatory responses, such as SIRT1, Nrf2, mTOR, and TGF-β, through complex and interrelated mechanisms. Due to these intricate connections, AMPK's role is pivotal in managing metabolic and inflammatory disorders. In this review, we demonstrate the specific roles of AMPK and its related pathways. Several agents directly activate AMPK by binding as agonists, while some others indirectly activate AMPK by modulating upstream molecules, including adiponectin, LKB1, and the AMP: ATP ratio. As AMPK activators can target each stage of MASLD progression, the development of AMPK activators offers immense potential to expand therapeutic strategies for liver diseases such as MASH, MASLD, and liver fibrosis.

Southern Schisandra is the dried and matured fruit of Schisandra sphenanthera Rehd. et Wils. in the family of Magnoliaceae; Traditional medicine reports that Schisandra sphenanthera has astringent and astringent properties, benefiting qi and promoting the production of body fluid, tranquilising the heart and calming the mind; it is clinically utilized for prolonged cough, thirst due to injury of the body fluid, internal heat and thirst, palpitation and insomnia, etc., and thirst belongs to the category of diabetes mellitus; the literature reports and the preliminary study of our team showed that Schisandra sphenanthera can be used to prevent and control diabetes mellitus.

In the research, we investigated the mechanism of action of SDP against T2DM by integrating pharmacodynamics, endogenous metabolite assays and signalling pathways.

UPLC-MS/MS was used to identify the chemical constituents. HPLC was utilized to determine the content of eight lignan-like components in SDP. A T2DM rat model was established by the combined induction of high-fat and high-sugar feed and STZ, and the mechanism of action of SDP on T2DM was investigated by using biochemical indices, Western blot analysis of protein expression, mRNA expression, immunohistochemistry and endogenous metabolites.

The chemical components in SDP were determined by UPLC-MS/MS and HPLC, and biochemical indicators determined that SDP has the effects of lowering blood glucose, anti-glycolipid metabolism, and anti-oxidative stress, and is able to restore pathological damage in the liver and pancreas, activate the PI3K/AKT, AMPK/mTOR, and sweetness receptor signalling pathways, restore the sweetness receptor mRNAs, and modulate the urinary compounds such as malic acid, γ-aminobutyric acid, leucine, N-acetylaspartic acid and other compounds thereby achieving the therapeutic effect of T2DM.

SDP can ameliorate diabetes-induced symptoms related to elevated blood glucose, dyslipidaemia, elevated fasting insulin levels and impaired glucose tolerance in rats; the anti-T2DM of SDP may be through the regulation of the sweet taste receptor pathway, the PI3K/AKT/mTOR and the AMPK/mTOR signalling pathway, which leads to the development of a normal level and exerts an antidiabetic effect.

Most tissues have the capacity for endogenous lipid synthesis. A crucial foundational pathway for lipid synthesis is de novo lipid synthesis (DNL), a ubiquitous and complex metabolic process that occurs at high levels in the liver, adipose and brain tissue. Under normal physiological conditions, DNL is vital in converting excess carbohydrates into fatty acids. DNL is linked to other pathways, including the endogenous synthesis of phospholipids and sphingolipids. However, abnormal lipid synthesis can contribute to various pathologies and clinical conditions. Experimental studies involving dietary restriction and in vivo genetic modifications provide compelling evidence demonstrating the significance of lipid synthesis in maintaining normal cardiovascular tissue function. Similarly, clinical investigations suggest altered lipid synthesis can harm cardiac and arterial tissues, thereby influencing cardiovascular disease (CVD) development and progression. Consequently, there is increased interest in exploring pharmacological interventions that target lipid synthesis metabolic pathways as potential strategies to alleviate CVD. Here we review the physiological and pathological impact of endogenous lipid synthesis and its implications for CVD. Since lipid synthesis can be targeted pharmacologically, enhancing our understanding of the molecular and biochemical mechanisms underlying lipid generation and cardiovascular function may prompt new insights into CVD and its treatment.

Proactively preventing postpartum weight retention (PPWR) is one of the effective intervention strategies to reduce the occurrence of obesity in women. Population studies have shown that serum folate levels are closely related to body weight. The regulation of folic acid on lipid metabolism has been fully confirmed in both in vivo and in vitro studies. For many years, folic acid supplementation has been widely used in periconceptional women due to its role in preventing fetal neural tube defects. However, whether folic acid supplementation prior to and throughout pregnancy exerts preventive effects on PPWR remains uncertain. This study aims to investigate the preventive effect of folic acid on PPWR in rats and further explore the underlying mechanisms.

In this study, pregnant rats were administered one of the dietary schedules: control diet (CON), high-fat diet (HF), control diet combined with folic acid (FA) and high-fat diet combined with folic acid (HF + FA).

We discovered that folic acid supplementation inhibited high-fat diet-induced elevations in body weight, visceral fat weight, liver weight, hepatic lipid levels and serum lipid levels at 1 week post-weaning (PW). Western blot analysis showed that folic acid supplementation inhibited the expression of endoplasmic reticulum (ER) stress-specific proteins including GRP78, PERK, eIF2α, IRE1α, XBP1 and ATF6, subsequently decreasing the expression of proteins related to lipid synthesis including SREBP-1c, ACC1 and FAS.

In conclusion, folic acid supplementation prior to and throughout pregnancy exerts preventive effects on high-fat diet-induced PPWR in rats, and the mechanism is associated with the inhibition of ER stress-mediated lipogenesis signaling pathways in the liver. Folic acid supplementation may serve as a potential strategy for preventing PPWR. In the future, the effectiveness of folic acid in PPWR prevention can be further verified by population studies.

Caloric Restriction (CR) and cinnamon promote several benefits, including the modulation of lipid metabolism and body fat mass. We hypothesize that cinnamon may act as a mimetic of restriction or enhance the effects of caloric restriction on adipose tissue. Adult male Wistar rats were divided into Control (CT, n = 8) and Cinnamon (CIN, n = 7), with free access to standard chow; Calorie Restriction (CR, n = 8) and Calorie Restriction with Cinnamon (CIN-CR, n = 7), subjected to a 30% reduction in food intake compared to the average consumption of CT rats. Both CIN groups received 50 mg cinnamon powder (Cinnamomun verum) per kg body mass, by gavage, over 6 weeks. Cinnamon treatment did not alter food intake under either ad libitum or caloric restriction conditions. The CR and CIN-CR groups exhibit lower body mass. Basal glycemia, lipid profile, and triglyceride-glycemic index were similar between groups. The combination of both interventions induced lower visceral white adipose tissue (WAT) mass, and smaller adipocyte diameter in the visceral and subcutaneous WAT compartments, accompanied by reduced expression of genes related to lipid metabolism (Acaca, Fasn, Cd36, Srebf1c), suggesting decreased lipid synthesis. Histological analyses identified a browning phenotype in the CR, CIN, and CIN-CR groups, positive for UCP1 immunostaining. The CR and CIN-CR groups showed lower Atg7 expression, and CIN-CR animals expressed increased levels of Lamp2, suggesting modulation of autophagy. Brown adipose tissue mass and lipid content were not influenced by any intervention. These findings suggest that cinnamon may enhance the effects of caloric restriction in promoting adipocyte metabolic health.

Adipose tissue vitamin A (VA), that is, mainly retinol (RET) and its esters, comes from preformed VA and proVA carotenoids present in our food. Adipose tissue VA acts as hormonal cue maintaining essential aspects of adipocyte biology, which includes fat mobilization and catabolism, energy balance, and glucose homeostasis, and it is thus of particular interest to study its determinants, including genetic ones.

This study aimed to identify genetic variations associated with adipose tissue VA concentration.

Forty-two healthy male adults received, in a randomized crossover design, 3 test meals. Periumbilical adipose tissue samples were collected on 6 occasions, that is, at fast and 8 h after consumption of each meal. RET concentration was measured in both plasma and the adipose tissue following saponification. Participants were genotyped using whole-genome microarrays. A total of 1305 single nucleotide polymorphism (SNPs) in or near 27 candidate genes were included for univariate analysis. Partial least squares (PLS) regression was carried out to find the best combination of SNPs associated with the interindividual variability in adipose tissue RET concentration.

Adipose tissue RET concentration was not associated with plasma RET concentrations (r = -0.184, P = 0.28). Interindividual variability of adipose tissue RET concentration was high (coefficient of variation = 62%). Twenty-nine SNPs were significantly (P < 0.05) associated with adipose tissue RET concentration and a PLS regression model identified 16 SNPs as explanatory variables of this concentration. The SNPs were in or near peroxisome proliferator activated receptor gamma, retinoid X receptor alpha, signaling receptor and transporter of retinol, cluster of differentiation 36, free fatty acid receptor 4, aldehyde dehydrogenase 1 family member A1, monoglyceride lipase, diacylglycerol O-acyltransferase 2, and polycystic kidney disease 1-like 2.

A combination of 16 SNPs has been associated with the interindividual of adipose tissue VA concentration in humans. This trial was registered at clinicaltrials.gov as NCT02100774.

Fatty liver hemorrhagic syndrome is the main cause of noninfectious death of laying hens and results in substantial economic losses to the poultry industry. This study focused on evaluating the effects of Poly-dihydromyricetin-fused zinc nanoparticles (PDMY-Zn NPs) on antioxidant capacity, liver lipid metabolism, and intestinal health in laying hens. A total of 288 Jingfen laying hens (52 wk old) with similar body weights were randomly divided into 4 dietary groups with 6 replicates in each group for 8 wk. The control group received a basal diet, while the treatment groups were supplemented with PDMY-Zn NPs at levels of 200, 400, and 600 mg/kg, respectively. The results indicate that PDMY-Zn NPs supplementation can enhance antioxidant parameters (P < 0.05) in the blood and liver of laying hens. Simultaneously, it can mitigate vacuolar degeneration and inflammatory necrosis in hepatocytes, improve the relative expression level of related parameters associated with liver lipid metabolism and key regulatory genes (P < 0.05). Furthermore, it has been observed to reshape the composition and diversity of cecum microbes by increasing beneficial probiotics such as Lactobacillus and Prevotella, while also enhancing villi height and villi/crypt ratio in the duodenum and ileum (P < 0.05). Additionally, it elevates liver bile acid content along with the relative expression of key genes involved in liver synthesis (P < 0.05). In summary, PDMY-Zn NPs showed potential to alleviate fatty liver hemorrhagic syndrome by enhancing antioxidant capacity, regulating liver lipid metabolism, and maintaining intestinal health.

This study aimed to characterize the relationship between habitual food intake and OSA.

The diet of 200 volunteers was evaluated using a Food Frequency Questionnaire. The patients were further allocated to mild, moderate, and severe OSA groups. The relationships of OSA with diet were evaluated using multivariate linear regression analysis and the relationships of the energy supply ratio for three major nutrients and demand with sleep parameters were assessed using correlation analysis.

The analysis of nutrient intake showed a reduced energy intake in non-OSA patients (11953.98 ± 7578.11 kJ, 95% CI 9677.27-14230.70 kJ) as compared to severe-OSA patients (15153.43 ± 6541.89 kJ, 95% CI 13678.46-16628.40 kJ) (p < 0.05). Similarly, lower intake of carbohydrates was observed in non-OSA (249.94 ± 134.96 g/day, 95% CI 209.39-290.48 g/day) as compared to severe OSA patients (348.57 ± 112.34 g/day, 95% CI 323.24-373.90 g/day) (p < 0.05). Compared with participants without OSA, we found that those with OSA had significantly poorer diets, with higher contents of rice (β = 0.195, p = 0.006), wheat (β = 0.236, p = 0.001), stuffed food items (β = 0.278, p < 0.001), fried food (β = 0.193, p = 0.006), dairy products (β = 0.198, p = 0.005), and sweet beverages (β = 0.154, p = 0.030). After adjustment for age, sex, the presence of diabetes, and waist-hip ratio, these relationships remained. Furthermore, a higher proportion of energy intake in the form of carbohydrate was associated with more severe OSA.

The severity of OSA is related to the level of carbohydrate consumption. Poor dietary habits predispose toward body mass gain and a worsening of sleep-related parameters, which may accelerate the pathogenesis of OSA.

Exercise has received considerable attention because of its importance not just in regulating physiological function, but also in ameliorating multiple pathological processes. Among these processes, lipolysis may play an important role in exercise-induced benefits. It is generally accepted that active lipolysis contributes to breakdown of fats, leading to the release of free fatty acids (FFAs) that serve as an energy source for muscles and other tissues during exercise. However, the significance of lipolysis in the context of exercise has not been fully understood. This review comprehensively outlines the potential regulatory mechanisms by which exercise stimulates lipolysis. The potential roles of exercise-mediated lipolysis in various physiological and pathological processes are also summarized. Additionally, we also discussed the potential non-classical effects of key lipolytic effectors induced by exercise. This will enhance our understanding of how exercise improves lipolytic function to bring about beneficial effects, offering new insights into potential therapeutic avenues for promoting health and alleviating diseases.

This study focused on evaluating the anti-obesity effects of an extract from Ampelopsis grossedentata (Hand.-Mazz.) W. T. Wang, also known as vine tea, in mature adipocytes and high-fat diet-induced obese mice. Vine tea extract (VTE) effectively decreased lipid accumulation in mature adipocytes without cytotoxicity, as confirmed by the regulation of several factors associated with adipogenesis, lipogenesis, or lipolysis. Subsequently, in a 12-week experiment with obese mice, oral VTE administration significantly reduced body weight gain induced with high-fat diet intake. Au-topsy findings showed reduced fat accumulation in various areas without liver damage. The VTE-administered group showed lower serum LDL levels, while increasing HDL, than the high-fat diet-administered group. Analysis of adipose tissue biomarkers indicated VTE's ability to inhibit adipogenesis and lipogenesis, promote lipolysis, and regulate energy metabolism, contributing to reduced adiposity induced by the consumption of a high-fat diet.

Metabolic dysfunction-associated steatotic liver disease (MASLD) represents a chronic liver disease. The development of MASLD is influenced by a multitude of diseases associated with modern lifestyles, including but not limited to diabetes mellitus, hypertension, hyperlipidaemia and obesity. These conditions are often consequences of the adoption of unhealthy habits, namely a sedentary lifestyle, a lack of physical activity, poor dietary choices and excessive alcohol consumption. The treatment of MASLD is primarily based on modifying the patient's lifestyle and pharmacological intervention. Despite the absence of FDA-approved pharmacological agents for the treatment of MASLD, several potential therapeutic modalities have demonstrated efficacy in reversing the histopathological features of the disease. Among the botanical ingredients belonging to the flavonoid group is quercetin (QE). QE has been demonstrated to possess a number of beneficial physiological effects, including anti-inflammatory, anticancer and antifungal properties. Additionally, it functions as a natural antioxidant. Preclinical evidence indicates that QE may play a beneficial role in reducing liver damage and improving metabolic health. Early human studies also suggest that QE may be an effective treatment for MASLD due to its antioxidant, anti-inflammatory, and lipid-regulating properties. This review aims to summarize the available information on the therapeutic effects of QE in MASLD.

S-Palmitoylation has been widely noticed and studied in a variety of diseases. Increasing evidence suggests that S-palmitoylation modification also plays a key role in Glioblastoma (GBM). The zDHHC family, as an important member of S-palmitoyltransferases, has received extensive attention for its function and mechanism in GBM which is one of the most common primary malignant tumors of the brain and has an adverse prognosis. This review focuses on the zDHHC family, essential S-palmitoyltransferases, and their involvement in GBM. By summarizing recent studies on zDHHC molecules in GBM, we highlight their significance in regulating critical processes such as cell proliferation, invasion, and apoptosis. Specifically, members of zDHHC3, zDHHC4, zDHHC5 and others affect key processes such as signal transduction and phenotypic transformation in GBM cells through different pathways, which in turn influence tumorigenesis and progression. This review systematically outlines the mechanism of zDHHC family-mediated S-palmitoylation modification in GBM, emphasizes its importance in the development of this disease, and provides potential targets and strategies for the treatment of GBM. It also offers theoretical foundations and insights for future research and clinical applications.