Adipose tissue demonstrates considerable plasticity and heterogeneity, enabling metabolic, cellular and structural adaptations to environmental signals. This adaptability is key for maintaining metabolic homeostasis. Impaired adipose tissue plasticity can lead to abnormal adipose tissue responses to metabolic cues, which contributes to the development of cardiometabolic diseases. In chronic obesity, white adipose tissue undergoes pathological remodelling marked by adipocyte hypertrophy, chronic inflammation and fibrosis, which are linked to local and systemic insulin resistance. Research data suggest that the capacity for healthy or unhealthy white adipose tissue remodelling might depend on the intrinsic diversity of adipose progenitor cells (APCs), which sense and respond to metabolic cues. This Review highlights studies on APCs as key determinants of adipose tissue plasticity, discussing differences between subcutaneous and visceral adipose tissue depots during development, growth and obesity. Modulating APC functions could improve strategies for treating adipose tissue dysfunction and metabolic diseases in obesity.

Cellular heterogeneity of human adipose tissue is linked to the pathophysiology of obesity and may impact the response to energy restriction and changes in fat mass. Herein, we provide an optimized pipeline to estimate cellular composition in human abdominal subcutaneous adipose tissue (ASAT) bulk RNA sequencing (RNA-seq) datasets using a single-nuclei RNA-seq signature matrix.

A deconvolution pipeline for ASAT was optimized by benchmarking publicly available algorithms using a signature matrix derived from ASAT single-nuclei RNA-seq data from 20 adults and then applied to estimate ASAT cell-type proportions in publicly available obesity and weight loss studies.

Individuals with obesity had greater proportions of macrophages and lower proportions of adipocyte subpopulations and vascular cells compared with lean individuals. Two months of diet-induced weight loss increased the estimated proportions of macrophages; however, 2 years of diet-induced weight loss reduced the estimated proportions of macrophages, thereby suggesting a biphasic nature of cellular remodeling of ASAT during weight loss.

Our optimized high-throughput pipeline facilitates the assessment of composition changes of highly characterized cell types in large numbers of ASAT samples using low-cost bulk RNA-seq. Our data reveal novel changes in cellular heterogeneity and its association with cardiometabolic health in humans with obesity and following weight loss.

While type 2 diabetes (T2DM) has become a major health issue in the North American and Caribbean region, the effects of weight change on incident T2DM, conditional on either initial or attained weight, are poorly addressed. Therefore, we aimed to assess the impact of 3-year weight change on incident T2DM over 6 years among US individuals.

A total of 8377 participants aged 45-64 years (4601 women), free of T2DM or cancer at baseline from the Atherosclerosis Risk in Communities (ARIC) study were included. Weight measurements were taken at baseline (visit 1, 1987-89) and approximately 3 years later (visit 2, 1990-92). Participants were categorised based on their weight change ratio into ≥ 5% weight loss, stable (±5%), and ≥ 5% weight gain. Cox proportional hazards models, adjusting for known diabetes risk factors, were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of incident T2DM, with stable weight (±5%) as the reference category.

During a median follow-up period of 6 years, participants were classified into three categories: 361 persons remained stable (±5%), 47 with ≥ 5% loss, and 135 with ≥ 5% gain. In multivariable analysis, after adjustment with initial weight, ≥ 5% weight gain and loss were significantly associated with higher [HR (95% CI): 1.68 (1.36-2.06), p-value < 0.0001] and lower [0.73 (0.53-1.00), p-value = 0.05] risks of incident T2DM, respectively. When adjusted for attained weight, weight gain ≥ 5% remained a significant risk factor for T2DM [1.51 (1.21-1.88)]; however, weight loss ≥ 5% lost statistical significance [0.84 (0.60-1.17), p-value = 0.31].

We found a robust association between weight gain and incident T2DM; however, the beneficial impact of weight loss was significantly attenuated after considering the attained weight.

Mycobacterium abscessus (M. abscessus) is an emerging, rapidly growing mycobacterium that causes chronic lung infection, particularly in patients with cystic fibrosis, as well as skin and soft tissue infections. Adipose tissue is recognized as an important niche that supports M. tuberculosis persistence. However, the dormancy, latency, and persistence mechanisms of M. abscessus in the host remain poorly understood. This study investigated how adipose tissue serves as a niche for M. abscessus using both a human adipose tissue ex vivo infection model and a murine adipose tissue in vivo infection model. M. abscessus infected not only the cytosol of adipocytes but also entered host lipid droplets, where it formed intracytoplasmic lipid inclusions in the bacterial cell. To our knowledge, this unique localization has never been reported for M. abscessus or any other mycobacterium. Within host lipid droplets, M. abscessus lost acid-fastness and gained Nile Red positivity. These results suggest that M. abscessus acquires a dormancy-like phenotype within host lipid droplets of adipocytes, potentially contributing to its persistence, virulence, and resistance to treatment. These findings provide valuable insights into mycobacterial persistence mechanisms and could offer a promising foundation for developing novel therapeutic approaches.

Dietary fat composition has changed substantially during the obesity epidemic. As adipocyte hyperplasia is a major mechanism of adipose expansion, we aim to ascertain how dietary fats affect adipogenesis during obesity. We employ an unbiased dietary screen to identify oleic acid (OA) as the only dietary fatty acid that induces obesogenic hyperplasia at physiologic levels and show that plasma monounsaturated fatty acids (MUFAs), which are mostly OA, are associated with human obesity. OA stimulates adipogenesis in mouse and human adipocyte precursor cells (APCs) by increasing AKT2 signaling, a hallmark of obesogenic hyperplasia, and reducing LXR activity. High OA consumption decreases LXRα Ser196 phosphorylation in APCs, while blocking LXRα phosphorylation results in APC hyperproliferation. As OA is increasingly being incorporated into dietary fats due to purported health benefits, our finding that OA is a unique physiologic regulator of adipose biology underscores the importance of understanding how high OA consumption affects metabolic health.

Obesity is a growing global epidemic associated with changes in the gut microenvironment and metabolic endotoxemia, which can exacerbate metabolic and inflammatory processes. Citral (CT), a monoterpene present in essential oils, has been investigated for its anti-inflammatory, antioxidant, and immunomodulatory properties. However, its role in modulating the gut axis during metabolic and inflammatory alterations in obesity remains unknown. In this study, we investigated the effects of CT on intestinal and metabolic impairment induced by lipopolysaccharide (LPS) and high-fat diet (HFD) in in vitro and in vivo models.

Male C57BL/6J mice were fed a standard diet and HFD for 17 weeks, with daily oral administration of CT treatment (25, 100, or 300 mg/kg) or vehicle. Morphological and histological parameters, lipid profiles, adipose index, cytokine levels, and colonic gene expression were determined. In vitro, murine rectal carcinoma (CMT-93) cells were stimulated with LPS (10 μg/mL) to assess tight junction and inflammatory protein expression.

CT treatment showed anti-obesity activity against HFD-induced body mass gain in mice, which was attributed to a significant reduction in body fat, glycemia, and cholesterol levels. Systemic inflammation during obesity also decreased after CT treatment, with a significant reduction in serum levels of endotoxin, interleukin-1β, and tumor necrosis factor-α. Additionally, CT stimulation reduced inducible nitric oxide synthase expression and maintained ZO-1 levels in LPS-stimulated CMT-93 cells.

CT has anti-obesogenic, anti-inflammatory, and anti-hyperlipidemic properties mediated by its protective effects on the intestinal epithelium in obesity. Thus, our results highlight the promising preclinical results of CT treatment as a protective agent against the detrimental effects of HFD and LPS in mice.

Obesity is recognized as a metabolic disorder, and its treatment and management pose ongoing challenges worldwide. Hawthorn, a traditional Chinese herb used to alleviate digestive issues and reduce blood lipid levels, has unclear mechanisms of action regarding its active components in the treatment of obesity. This study investigated the anti-obesity effects of vitexin, a major flavonoid compound found in hawthorn, in high-fat diet (HFD)-induced C57BL/6 mice. The results demonstrated that vitexin significantly reduced body weight, liver weight, blood lipid levels, and inflammatory markers in obese mice, while also inhibiting hepatic lipid accumulation. Mechanistic studies revealed that vitexin likely suppresses adipogenesis by modulating the PI3K-AKT signaling pathway, as evidenced by reduced expression of PI3K, phosphorylated AKT, phosphorylated mTOR, and SREBP-1c in the livers of vitexin-treated obese mice. Additionally, vitexin inhibited NFκB expression by regulating IκBα phosphorylation, thereby alleviating obesity-induced liver injury. These findings suggest that vitexin may be the primary active component in hawthorn responsible for reducing blood lipid levels, highlighting its potential in the treatment of obesity and its associated metabolic disorders.

White adipose tissue (WAT) is highly flexible and was previously considered a passive location for energy storage. Its endocrine function has been established for several years, earning it the title of an "endocrine organ" due to its ability to secrete many adipokines that regulate metabolism. WAT is one of the core tissues that influence insulin sensitivity. Its dysfunction enhances insulin resistance and type 2 diabetes (T2D) progression. However, T2D may cause WAT dysfunction, including changes in distribution, metabolism, adipocyte hypertrophy, inflammation, aging, and adipokines and free fatty acid levels, which may exacerbate insulin resistance. This review used PubMed to search WAT dysfunction in T2D and the effects of these changes on insulin resistance. Additionally, we described and discussed the effects of antidiabetic drugs, including insulin therapy, sulfonylureas, metformin, glucose-like peptide-1 receptor agonists, thiazolidinediones, and sodium-dependent glucose transporters-2 inhibitors, on WAT parameters under T2D conditions.

Colorectal cancer (CRC) is the third most common cancer worldwide and has one of the highest mortality rates. Considering its nonlinear etiology, many risk factors are associated with CRC formation and development, with obesity at the forefront. Obesity is regarded as one of the key environmental risk determinants for the pathogenesis of CRC. Excessive food intake and a sedentary lifestyle, together with genetic predispositions, lead to the overgrowth of adipose tissue along with a disruption in the number and function of its building cells. Adipose tissue-resident cells may constitute part of the CRC microenvironment. Alterations in their physiology and secretory profiles observed in obesity may further contribute to CRC progression, and despite similar localization, their contributions are not equivalent. They can interact with CRC cells, either directly or indirectly, influencing various processes that contribute to tumorigenesis. The main aim of this review is to provide insights into the diversity of adipose tissue resident cells, namely, adipocytes, adipose stromal cells, and immunological cells, regarding the role of particular cell types in co-forming the CRC microenvironment. The scope of this study was also devoted to the abnormalities in adipose tissue physiology observed in obesity states and their impact on CRC development.

Switching between different foods while eating has been positively associated with weight status and intake in children. Evidence suggests that switching behavior is consistent within children across meals, however, it is unclear how switching relates to changes in adiposity over time. In a 1-year longitudinal study, we assessed whether food switching predicted changes in fat mass index (FMI: fat mass kg/height m2) in 7-8-year-old children and tested if familial risk of obesity moderated this relationship. At baseline, seventy-four children without obesity (7.8 ± 0.6 y; 37F) consumed four ad libitum meals of varying portion sizes, each consisting of chicken nuggets, macaroni and cheese, grapes, and broccoli. For each child, the average number of food switches was calculated from video recordings across the four meals. To assess change in adiposity over time, children completed a dual energy x-ray absorptiometry scan for assessment of FMI at baseline and follow-up (≥1 year later). Familial risk of obesity was determined by maternal BMI (high-risk: ≥30 kg/m2, n = 32 vs. low-risk: <25 kg/m2, n = 42). Food switching at baseline was positively associated with changes in FMI over 1 year (p = 0.03). In addition to the 37% of variance in FMI change explained by known factors influencing adiposity, food switching accounted for an additional 4% of the variance (p = 0.03). Further, there was an interaction between familial risk status and food switching (p = 0.04) such that the relationship between switching and FMI change was only significant in high-risk children. Overall, children's food switching behavior assessed at laboratory meals predicted change in adiposity over 1 year. Food switching could be a behavioral marker for, and contribute to, pediatric obesity risk particularly in children with a familial predisposition.

Adipocyte size and number (cellularity) determine the adipose mass and may relate to long-term body weight changes.

We investigated 1014 healthy participants at Karolinska Institutet in Sweden 1988-2016 for body weight and size/number of subcutaneous adipocytes, and 273 for visceral adipocyte size. We measured body weight on 281 subjects about 16 years later. We analysed the association of baseline adipocyte size and number with body weight changes by linear regression including relevant co-factors, and the associations of cellularity (low or high number of either large or small adipocytes) regarding body weight changes by analysis of variance.

Subcutaneous adipocyte size and number and visceral adipocyte size showed strong relationships with body weight changes irrespective of its mode of expression (adjusted r2 ≥0·15). The relationships were significant (p ≤ 0·027) independent of co-factors (age, sex, initial body weight or height, body fat, obesity, nicotine use, physical activity, and observation time). Interventions (lifestyle change or bariatric surgery) did not influence the associations (p = 0·86). A low or high number of large adipocytes associated with body weight loss, whereas a low or high number of small cells associated with weight stability or weight gain.

Adipose cellularity is associated with long-term changes in body weight, following interventions to decrease body weight. Patients with a high number of large fat cells experienced the most pronounced weight reduction.

The Stockholm County Council (963296, 994175, 986118), the Center for Innovative Medicine at Karolinska Institutet (986109) and the Swedish Society of Medicine (1001156). None of the funding sources had any involvement in the study.

Gestational diabetes mellitus (GDM) is a complication that affects 20% of pregnancies worldwide. It is associated with adverse short- and long-term cardiometabolic outcomes for both mother and infant. Effective management of GDM involves lifestyle modifications, including medical nutrition therapy (MNT) and physical activity (PA), with the addition of insulin or metformin if glycaemic control remains inadequate. However, substantial gaps persist in the determination of optimal medical nutrition therapy (MNT) for women with GDM. Challenges in MNT include individual variation in glucose tolerance and changing maternal physiology and dietary requirements during pregnancy. Achieving optimal glycaemic control depends on careful macronutrient balance, particularly the distribution and quality of carbohydrate intake and sufficient protein and fat intake. Additionally, micronutrient deficiencies, such as inadequate vitamin D, calcium, and essential minerals, may exacerbate oxidative stress, inflammation, and glycaemic dysregulation, further impacting foetal growth and development. Cultural beliefs and dietary practices among pregnant women can also hinder adherence to recommended nutritional guidelines. Conditions like hyperemesis gravidarum (HG) affect ~1% to 2% of pregnant women can result in unintended energy and nutrient deficits. This special issue explores the current evidence and major barriers to optimising dietary therapy for women with GDM. It also identifies future research priorities to advance clinical practice, improve maternal and foetal outcomes, and address gaps in personalised nutrition interventions.

Adipose tissue expands through hyperplasia and hypertrophy to store excess lipids, a process that is essential for the maintenance of metabolic homeostasis. The mechanisms regulating adipocyte recruitment from progenitors remain unclear. We have previously identified V-set and transmembrane domain-containing protein 2A (VSTM2A) as a factor promoting fat cell development in vitro. Whether VSTM2A impacts adipose tissue and systemic metabolism in vivo is still unknown.

We generated VSTM2A knockout mice (Vstm2a-/-) using clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) and fed them either a chow or high-fat diet. These mice were evaluated for body weight, adiposity, blood parameters, and glucose homeostasis.

Vstm2a-/- mice were viable and showed no body weight differences. Although adipose mass was similar, Vstm2a-/- mice had larger adipocytes, an effect linked to inflammation, ectopic lipid deposition, and impaired glucose and lipid metabolism. Transcriptomic analysis revealed that VSTM2A loss affects the expression of several genes in adipose tissue, including some related to the lysosome. Interestingly, acute lysosomal inhibition early in life is sufficient to cause adipocyte hypertrophy in adults.

VSTM2A is dispensable for adipose tissue formation, but its loss causes adipocyte hypertrophy and impairs glucose and lipid homeostasis. Our study also underscores a critical role of the lysosome in initiating adipogenesis.

Biological accelerator mass spectrometry (AMS) provides ultrasensitive carbon-14 isotopic analysis enabling a deeper understanding of human health concerns by enabling quantification of pharmacokinetics and other molecular endpoints directly in humans. It enables environmentally and human relevant studies of metabolic pathways through the use of very low concentrations of labeled metabolic substrates in cells and organisms. Here, we discuss why AMS is an important tool for the biosciences, the development and evolution of biological AMS at Livermore and discuss technical refinements that will improve the efficiency of operation for the measurement of ultra-trace levels of 14C, which, long term, will enable greater ease of use and sample throughput.

The transition from metabolically healthy obesity to the development of obesity-associated metabolic syndrome and cardiovascular disease is thought to be triggered by a loss in the functional integrity of adipose tissue. Although mature adipocytes are the primary functional units that carry out lipid partitioning in adipose tissue for the promotion of whole-body energy balance, they are supported by a heterogenous collection of nonadipocytes in the stroma. Research over the past couple of decades has expanded perspectives on the homeostatic and pathological roles of the nonadipocyte compartment. Adipose progenitors originate in the embryonic period and drive the developmental adipogenesis that establishes the set point of adiposity. A population of adipocyte progenitors reside in adult depots and serve an important homeostatic role as a reservoir to support adipocyte turnover. Adipocyte hypertrophy in obesity increases the rate of adipocyte death and the ability of progenitors to support this high rate of adipocyte turnover is important for the preservation of the lipid-buffering function of adipose tissue. Some evidence exists to suggest that impaired adipogenesis or a decline in progenitors capable of differentiation is a key event in the development of adipose dysfunction. The efficiency of macrophages to clear the debris and toxic lipids released from dead adipocytes lies at the fulcrum between preservation of adipose function and the progression toward chronic inflammation. Although macrophages in collaboration with other immune cells propagate the inflammation that underlies adipose dysfunction, there is now a greater appreciation for the diverse and unique roles of immune cells within adipose tissue.

Fat distribution and macro structure of white adipose tissue are important factors in predicting obesity-associated diseases, but cellular microstructure of white adipose tissue has been less explored. To investigate the relationship between adipocyte size and obesity-related traits, and their underlying disease-driving genetic associations, we performed the largest study of automatic adipocyte phenotyping linking histological measurements and genetics to date. We introduce deep learning based methods for scalable and accurate semantic segmentation of subcutaneous and visceral adipose tissue histology samples (N=2,667) across 5 independent cohorts, including data from 9,000 whole slide images, with over 27 million adipocytes. Estimates of mean size of adipocytes were validated against Glastonbury et al. 2020. We show that adipocyte hypertrophy correlates with an adverse metabolic profile with increased levels of leptin, fasting plasma glucose, glycated hemoglobin and triglycerides, and decreased levels of adiponectin and HDL cholesterol. We performed the largest GWAS (N Subcutaneous = 2066, N Visceral = 1878) and subsequent meta-analysis of mean adipocyte area, and find two genome-wide significant loci (rs73184721, rs200047724) associated with increased 95%-quantile adipocyte size in respectively visceral and subcutaneous adipose tissue. Stratifying by sex, in females we find two genome-wide significant loci, with one variant (rs140503338) associated with increased mean adipocyte size in subcutaneous adipose tissue, and the other (rs11656704) is associated with decreased 95%-quantile adipocyte size in visceral adipose tissue.

Plastic materials are ubiquitous, leading to constant human exposure to plastic additives such as plasticizers. There is growing evidence that plasticizers may contribute to obesity due to their disruptive effects on metabolism. Alternatives like diisononylcyclohexane-1,2-dicarboxylate (DINCH) are replacing traditional phthalates such as di-(2-ethylhexyl) phthalate (DEHP), which are now banned due to their proven harmful health effects. While DINCH is considered a safer alternative to DEHP and no adipogenic effects have been demonstrated in in vivo studies, recent research suggests that the primary metabolite, monoisononylcyclohexane-1,2-dicarboxylic acid ester (MINCH), promotes adipocyte differentiation and dysfunction in vitro. However, metabolic and molecular effects are not fully understood in vivo. Here, we performed a comprehensive in vivo analysis using C57BL/6N mice to investigate the effects of DINCH on adipose tissue physiology and function. Mice were exposed to two doses of DINCH for 16 weeks, followed by a 10-week recovery period. Tissue analysis confirmed the presence of DINCH and MINCH in liver and adipose tissue after treatment and recovery. After the recovery period, elevated DINCH concentrations in adipose tissue depots indicated possible bioaccumulation. Although no changes were observed in body composition and energy expenditure, sex-specific metabolic effects were identified. Female mice exhibited impaired whole-body insulin sensitivity and higher triglyceride levels, while male mice showed an altered insulin/C-peptide ratio and elevated cholesterol, HDL, and LDL levels. Proteomic profiling of serum, adipose and liver tissues revealed changes in pathways related to central energy metabolism and immune response, highlighting the systemic impact of DINCH, potentially on inflammatory processes. Most effects of DINCH, such as changes in insulin response and serum lipid levels, were diminished after the recovery period. Despite many findings consistent with the existing literature suggesting DINCH as a safer DEHP substitute, the observed sex-specific effects on insulin sensitivity, lipid metabolism and inflammatory processes, as well as potential bioaccumulation and long-term metabolic effects of DINCH exposure warrant careful consideration in further risk assessment.

Cellular turnover is fundamental for tissue homeostasis and integrity. Adipocyte turnover, accounting for 4% of the total cellular mass turnover in humans, is essential for adipose tissue homeostasis during metabolic stress. In obesity, an altered adipose tissue microenvironment promotes adipocyte death. To clear dead adipocytes, macrophages are recruited and form a distinctive structure known as crown-like structure; subsequently, new adipocytes are generated from adipose stem and progenitor cells in the adipogenic niche to replace dead adipocytes. Accumulating evidence indicates that adipocyte death, clearance, and adipogenesis are sophisticatedly orchestrated during adipocyte turnover. In this Review, we summarize our current understandings of each step in adipocyte turnover, discussing its key players and regulatory mechanisms.

This study employed lipidomics to investigate the effects of varying lysine (Lys)- to-methionine (Met) ratios on the antioxidant capacity, tissue morphology, and fatty acid composition of subcutaneous fat in Tibetan sheep fed a low-protein diet.

Ninety healthy male Tibetan sheep of similar body weight were randomly allocated into three groups. These sheep were fed a low-protein diet containing Lys/Met ratios of 1:1, 2:1, and 3:1. Ultra-High Performance Liquid Chromatography-tandem Mass Spectrometry (UHPLC-MS/MS) was employed to explore the changes in various lipid subclasses in subcutaneous adipose tissue. The expression of genes associated with adipogenesis, antioxidant capacity, and fatty acid metabolism was also examined.

The results indicated that the 1:1 Lys/Met group exhibited significantly higher antioxidant capacity (glutathione peroxidase, GSH-Px), with more orderly adipocyte arrangement, uniform cell size, and a general increase in unsaturated fatty acid levels. Additionally, several lipid molecules associated with the phenotype (Antioxidant index and fatty acid content) were identified, namely, DG(38:3e) + Na, PE(17:1_22:2)-H, PI(17:0_20:3)-H, TG(33:0e) + NH4, Cer(d14:0_17:1) + H, and CL(81:13)-2H. Furthermore, the findings showed that the upregulation of PPARγ, FASN, FAD4, CPT1A, and GPX4 can enhance adipocyte differentiation and lipid accumulation, thereby improving metabolic function in subcutaneous adipose tissue via the regulation of lipid metabolism and oxidative defense mechanisms.

In summary, this study provides a theoretical foundation for optimizing precision feeding strategies for Tibetan sheep, offering crucial data to support enhancements in production efficiency and meat quality.

Excessive abdominal fat deposition in chickens disadvantages feed conversion, meat production, and reproductive performance. Intramuscular fat contributes to meat texture, tenderness, and flavor, serving as a vital indicator of overall meat quality. Therefore, a comprehensive analysis of the regulatory mechanisms governing differential deposition of abdominal versus intramuscular fat is essential in breeding higher-quality chickens with ideal fat distribution. This review systematically summarizes the regulatory mechanisms underlying intramuscular and abdominal fat traits at chromatin, genomic, transcriptional, post-transcriptional, translational, and epigenetic-modification scales. Additionally, we summarize the role of non-coding RNAs and protein-coding genes in governing intramuscular and abdominal fat deposition. These insights provide a valuable theoretical foundation for the genetic engineering of high-quality and high-yielding chicken breeds.

Epidemiological surveys indicate an increasing incidence of type 2 diabetes mellitus (T2DM) among children and adolescents worldwide. Due to rapid disease progression, severe long-term cardiorenal complications, a lack of effective treatment strategies, and substantial socioeconomic burdens, it has become an urgent public health issue that requires management and resolution. Adolescent T2DM differs from adult T2DM. Despite a significant increase in our understanding of youth-onset T2DM over the past two decades, the related review and evidence-based content remain limited.

To visualize the hotspots and trends in pediatric and adolescent T2DM research and to forecast their future research themes.

This study utilized the terms "children", "adolescents", and "type 2 diabetes", retrieving relevant articles published between 1983 and 2023 from three citation databases within the Web of Science Core Collection (SCI, SSCI, ESCI). Utilizing CiteSpace and VoSviewer software, we analyze and visually represent the annual output of literature, countries involved, and participating institutions. This allows us to predict trends in this research field. Our analysis encompasses co-cited authors, journal overlays, citation overlays, time-zone views, keyword analysis, and reference analysis, etc.

A total of 9210 articles were included, and the annual publication volume in this field showed a steady growth trend. The United States had the highest number of publications and the highest H-index. The United States also had the most research institutions and the strongest research capacity. The global hot journals were primarily diabetes professional journals but also included journals related to nutrition, endocrinology, and metabolism. Keyword analysis showed that research related to endothelial dysfunction, exposure risk, cardiac metabolic risk, changes in gut microbiota, the impact on comorbidities and outcomes, etc., were emerging keywords. They have maintained their popularity in this field, suggesting that these areas have garnered significant research interest in recent years.

Pediatric and adolescent T2DM is increasingly drawing global attention, with genes, behaviors, environmental factors, and multisystemic interventions potentially emerging as future research hot spots.

Obesity is a critical risk factor for the development of metabolic diseases and is often associated with dysfunctional adipocytes. Prevalent treatments such as lifestyle intervention, pharmacotherapy, and bariatric surgery are often accompanied by adverse side effects and poor patient compliance. Nanotechnology and cell-based therapy offer innovative approaches for targeted obesity treatments, as they can directly target adipocytes, regulate lipid metabolism, and minimize off-target effects. Here, we provide an overview of the intricate relationship between adipocytes and obesity, highlighting the potential of nanotechnology and cell-based therapy in obesity treatment. Additionally, we discuss the advancements of adipose-derived mesenchymal stem cells (ADMSCs) in obesity progression, including the latest challenges and considerations for developing adipose-targeted treatments for obesity. The objective is to provide a perspective on the design and development of nanotechnology and cell-based therapy for treating obesity and related comorbidities.

While previous studies have explored the relationship between obesity and levels of thyroid autoantibodies, research using novel indicators such as weight-adjusted waist index (WWI) remains limited. This study aimed to evaluate the potential relationship between WWI and thyroid autoantibody levels, with the objective of improving our understanding of the links between central obesity and Hashimoto's thyroiditis (HT).

We conducted a cross-sectional study using data from the National Health and Nutrition Examination Survey (NHANES) cycles from 2007 to 2012. We analyzed the relationship between WWI and levels of thyroid peroxidase antibodies (TPOAb) and thyroglobulin antibodies (TgAb) through multivariate linear regression and subgroup analyses.

The study included 7,056 participants with an average age of 49.71 ± 17.66 years, comprising 49.18% females. Mean WWI across the cohort was 11.04 ± 0.84. Analysis revealed a significant positive association between WWI and TPOAb levels (β: 4.78, 95% CI: 1.52, 8.05, p = 0.0041), which remained consistent across all multivariate linear regression models. In contrast, no significant correlation was found between WWI and TgAb levels after adjusting for covariates. Subgroup analysis stratified by gender demonstrated a notable gender-specific effect, where the positive correlation between WWI and TPOAb levels was evident only in females (β: 8.13, 95% CI: 4.14, 12.12, p < 0.0001).

This study used WWI as a novel indicator of central obesity and identified a strong association with HT, particularly notable in females. However, further high-quality studies are needed to confirm these findings and explore the underlying biological mechanisms.

To investigate the modifying role of obesity in the association between abnormal glucose metabolism and atrial fibrillation (AF) risk in older individuals.

From April 2007 to November 2011, 11,663 participants aged ≥60 years were enrolled in the Shandong area. Glucose metabolic status was determined using fasting plasma glucose and hemoglobin A1c levels, and obesity was determined using body mass index (BMI), waist-to-hip ratio (WHR), and visceral fat area (VFA). Obesity-associated metabolic activities were assessed using the adiponectin-to-leptin ratio (ALR), galectin-3, and triglyceride-glucose index (TyG). New-onset AF was diagnosed by ICD-10.

During an average of 11.1 years of follow-up, 1343 participants developed AF. AF risks were higher in those with prediabetes, uncontrolled diabetes, and well-controlled diabetes than with normoglycemia. The hazard ratios were decreased by 14.79%, 40.29%, and 25.23% in those with prediabetes; 31.44%, 53.56%, and 41.90% in those with uncontrolled diabetes; and 21.16%, 42.38%, and 27.59% in those with well-controlled diabetes after adjusting for BMI, WHR, and VFA, respectively. The population-attributable risk percentages of general obesity, central obesity, and high VFA for new-onset AF were 10.43%, 34.78%, and 31.30%, respectively. ALR, galectin-3, and TyG significantly mediated the association of BMI, WHR, and VFA with AF risk (all Padj. < 0.001).

Obesity mediates the association between abnormal glucose metabolism and AF risk in older individuals. WHR is a more effective modifier than BMI and VFA for moderating the association. ALR, TyG, and galectin-3 mediate the moderating effect of obesity on the association between abnormal glucose metabolism and AF risk.

High-fat diet (HFD) contributes to obesity and enhances the expression of mature adipocyte markers. However, the effect of HFD on adipocyte hyperplasia remains controversial. This may be due to variations in the duration of HFD. This study aimed to investigate the effects of different durations of HFD on adipocyte hyperplasia and the expression of mature adipocyte-related markers in obese rats.

We divided 32 Sprague-Dawley rats into four groups: B (standard diet control), H1 (HFD for four weeks), H2 (HFD for eight weeks), and H3 (HFD for 12 weeks). We evaluated the morphological changes in epididymal fat cells, measured serum inflammatory markers using enzyme-linked immunosorbent assay (ELISA) kits, and quantified adipocyte hyperplasia and maturation markers using western blotting.

We observed progressive increases in body weight, epididymal fat weight, serum leptin, TNF-α, IL-6, irisin, PPARγ, adiponectin, and FNDC5 protein expression over 8 weeks of HFD. 12 weeks of HFD intervention resulted in significant decreases in irisin, PPARγ, adiponectin, and FNDC5. Concurrently, the expression of perilipin A and ATGL declined with prolonged HFD.

Our results suggest that the duration of HFD significantly affects adipocyte ability to undergo hyperplasia in the epididymis of obese rats. Specifically, 4 weeks of HFD did not change the capacity for adipocyte hyperplasia, while 8 weeks of the diet enhanced this capacity. Interestingly, a longer diet duration (12 weeks) led to a decrease in adipocyte hyperplasia.

Adipose-derived lipid droplets (LDs) are rich in triacylglycerols (TAGs), which regulate essential cellular processes, such as energy storage. Although TAG accumulation and LD expansion in adipocytes occur during obesity, how LDs dynamically package TAGs in response to excessive nutrients remains elusive. Here, we found that LD lipidomes display a remarkable increase in TAG acyl chain saturation under calorie-dense diets, turning them conducive to close-packing. Using high-resolution X-ray diffraction, solid-state NMR, and imaging, we show that beyond size expansion LDs from mice under varied obesogenic diets govern fat accumulation by packing TAGs in different crystalline polymorphs. Consistently, LDs and tissue stiffen for high-calorie-fed mice with more than a 2-fold increase in elastic moduli compared to normal diet. Our data suggest that in addition to expanding, adipocyte LDs undergo structural remodeling by close-packing rigid and highly saturated TAGs in response to caloric overload, as opposed to liquid TAGs in a low-calorie diet. This work provides insights into how lipid packing within LDs can allow for the rapid and optimal expansion of fat during the initial stages of obesity.

Age-dependent changes in adipose tissue are thought to play a role in development of insulin resistance. A major age-dependent change in adipose tissue is the downregulation of key proteins involved in carbohydrate metabolism. In the current study, we investigate the role of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3) a key governor of the rate of glycolysis in adipocytes via the synthesis of fructose-2,6-bisphosphate that was significantly downregulated in aged mice. We employed an adipocyte-specific PFKFB3 mouse line to investigate the role of PFKFB3 on adipocyte function. In both aged mice and PFKFB3-knockout mice, we observed an increase in O-glcNAcylated proteins consistent with a shift in glucose metabolism toward the hexosamine biosynthetic pathway. Under chow-fed conditions, PFKFB3 knockout resulted in significantly smaller adipocyte area, but no difference in total fat mass. While glucose tolerance was unchanged under chow conditions, when mice were challenged with a 4 weeks high-fat feeding, PFKFB3 deletion led to a greater decrease in glucose tolerance as well as a significant increase in macrophage infiltration. These results indicate that perturbation of the glycolytic pathway in adipose tissue has multiple effects of adipocyte biology and may play a significant role in metabolic changes associated with aging. Results of this student support the notion that changes in glucose metabolism in adipose tissue impact whole-body metabolism.

Wingless-type inducible signaling pathway protein-1 (WISP1) is a newly recognized adipokine, associated with obesity and type 2 diabetes (T2DM). This study aimed to investigate the effect of metabolic and bariatric surgery (MBS) on WISP1 circulating (serum) levels and tissue expression using rat models. We initially investigated whether WISP1 circulating levels were altered between the T2DM and normal rats. After confirmation, Sprague-Dawley (SD) rats were obtained and randomly divided as follows: Roux-en-Y gastric bypass (RYGB) group (n = 10), sleeve gastrectomy (SG) group (n = 10), SHAM group (n = 10), and normal control (NC) group (n = 10). Rats were followed for 8 weeks postoperatively. Preoperative and postoperative WISP1 circulating (serum) levels, glucose tolerance test (OGTT), insulin tolerance test (ITT), postoperative WISP1 expression (visceral adipose tissue, VAT; and skeletal muscle, SM), body weight, food intake, and fasting blood glucose levels were recorded. MBS significantly induced glucose control and weight loss. At postoperative week 8, WISP1 serum levels decreased in the MBS groups (P < 0.05); furthermore, WISP1 expression in VAT and SM significantly decreased in the RYGB and SG groups than SHAM (P < 0.05, and P < 0.05, respectively). Whereas the difference in the expression level between SG and RYGB did not amount to statistical significance (P > 0.05). MBS significantly decreased WISP1 serum levels, tissue expression in the VAT, and SM. As WISP1 is a regulator of low-grade inflammation associated with obesity and T2DM, further studies are needed to explore its relevance in MBS.

Fat content is the main criterion for evaluating albacore quality. However, no reports exist on the accuracy of the tail-cutting method, a method used to assess the fat content of albacore. Here, we evaluated this method by comparing it with chemical analysis and ultrasound inspection. We measured the actual fat content in albacore using chemical analysis and compared the results with those obtained using the tail-cutting method. Significant discrepancies (99% CI, t-test) were observed in fat content among the tail-cutting samples. Using chemical analysis as the ground truth, the accuracy of tail-cutting from two different companies was 70.0% for company A and 51.9% for company B. An ultrasound inspection revealed that a higher fat content reduced the amplitude of ultrasound signals with statistical significance (99% CI, t-test). Finally, machine learning algorithms were used to enforce the ultrasound inspection. The best combination of ultrasound inspection and a machine learning algorithm achieved an 84.2% accuracy for selecting fat-rich albacore, which is better than tail-cutting (73.6%). Our findings suggested that ultrasound inspection could be a valuable and non-destructive method for estimating the fat content of albacore, achieving better accuracy than the traditional tail-cutting method.

Adipose tissue has an established endocrine function through the secretion of adipokines. However, a role for bioactive metabolites and lipids, termed metabokines and lipokines, is emerging in adipose tissue-mediated autocrine, paracrine and endocrine signalling and inter-organ communication. Traditionally seen as passive entities, metabolites are now recognized for their active roles in regulating cellular signalling and local and systemic metabolism. Distinct from white adipose tissue, specific endocrine functions have been attributed to thermogenic brown and beige adipose tissues. Brown and beige adipose tissues have been identified as sources of metabokines and lipokines, which influence diverse metabolic pathways, such as fatty acid β-oxidation, mitochondrial function and glucose homeostasis, across a range of tissues, including skeletal muscle, adipose tissue and heart. This review explores the intricate signalling mechanisms of brown and beige adipose tissue-derived metabokines and lipokines, emphasizing their roles in maintaining metabolic homeostasis and their potential dysregulation in metabolic diseases. Furthermore, we discuss the therapeutic potential of targeting these pathways, proposing that precise modulation of metabokine receptors and transporters could offer superior specificity and efficacy in comparison to conventional approaches, such as β-adrenergic signalling-stimulated activation of brown adipose tissue thermogenesis. Understanding the complex interactions between adipokines, metabokines and lipokines is essential for developing a systems-level approach to new interventions for metabolic disorders, underscoring the need for continued research in this rapidly evolving field.

The molecular mechanisms linking obstructive sleep apnea syndrome (OSA) to obesity and the development of metabolic diseases are still poorly understood. The role of hypoxia (a characteristic feature of OSA) in excessive fat accumulation has been proposed. The present study investigated the possible effects of hypoxia (4% oxygen) on de novo lipogenesis by tracking the major carbon sources in differentiating 3T3-L1 adipocytes. Gas-permeable cultuware was employed to cultivate 3T3-L1 adipocytes in hypoxia (4%) for 7 or 14 days of differentiation. We investigated the contribution of glutamine, glucose or acetate using 13C or 14C labelled carbons to the newly synthesized lipid pool, changes in intracellular lipid content after inhibiting citrate- or acetate-dependent pathways and gene expression of involved key enzymes. The results demonstrate that, in differentiating adipocytes, hypoxia decreased the synthesis of lipids from glucose (44.1 ± 8.8 to 27.5 ± 3.0 pmol/mg of protein, p < 0.01) and partially decreased the contribution of glutamine metabolized through the reverse tricarboxylic acid cycle (4.6% ± 0.2-4.2% ± 0.1%, p < 0.01). Conversely, the contribution of acetate, a citrate- and mitochondria-independent source of carbons, increased upon hypoxia (356.5 ± 71.4 to 649.8 ± 117.5 pmol/mg of protein, p < 0.01). Further, inhibiting the citrate- or acetate-dependent pathways decreased the intracellular lipid content by 58% and 73%, respectively (p < 0.01) showing the importance of de novo lipogenesis in hypoxia-exposed adipocytes. Altogether, hypoxia modified the utilization of carbon sources, leading to alterations in de novo lipogenesis in differentiating adipocytes and increased intracellular lipid content.

The excessive accumulation of adipose tissue in obesity appears to result in adipose tissue dysfunction perpetuating the onset of obesity-related diseases, including type 2 diabetes (T2DM). In humans, adipose tissue is stored in several depots including subcutaneous and visceral. These depots contribute to the pathology of obesity differently owing to differences in the tissue microenvironment, a main one being preadipocyte function. In examining adipocyte and preadipocyte characteristics, many have used the 3T3-L1 murine cell lines. Though these cell lines provide valuable mechanistic data, the results remain to be translated to humans. Experiments using primary human preadipocytes has shown that obesity and T2DM impact preadipocyte phenotypes. The objective of this review is to describe the differences in regional characteristics of primary preadipocytes collected from humans with obesity and to discuss how these characteristics might be affected in type 2 diabetes mellitus. In doing so, we will show that the characteristics of regional primary preadipocytes in humans are differentially affected by obesity and the development of T2DM.

Obesity is a global public health problem that can lead to mortality and morbidity. Studies on the pathophysiology of obesity for effective and safe treatments are focused on the mechanisms of adipogenesis. The association between boron treatment and weight loss has been reported, but its anti-adipogenic mechanisms and effects on preadipocytes remain unclear. This study aims to investigate the effects of boron compounds boric acid (BA) and calcium fructoborate (CaFB) on adipogenesis using the most widely used in vitro 3T3-L1 cellular model. In our study, cytotoxicity, Oil Red O (ORO), gene and protein expression analyses and cellular NAD measurements of boron compounds were performed. Peroxisome proliferator-activated receptor γ (PPARγ) and CCAAT/enhancer binding protein α (C/EBPα) transcription factors are the main regulators of adipogenesis, and boron compounds affect them at gene and protein levels by showing anti-obesity effects. This is the first study to show that CaFB has anti-obesity properties in mouse adipocytes. Sirtuins, known as the longevity genes, were also activated from boron treatment. Results of this research provide new basic knowledge and insights into the effect of boron-based compounds on obesity. It also offers potential prospects for the development of effective treatment and/or supportive treatment methods.

Adipose tissue is a large endocrine organ that serves numerous physiological functions. As we age, adipose tissue remodels and can develop functional changes that alters its phenotype, potentially contributing to metabolic and cardiovascular disorders. Aging adipose tissue is characterized by regional redistribution of fat, accumulation of senescent cells, fibrosis, and decline in adipocyte differentiation capacities, which collectively impact adipose tissue function and whole body health. A notable transformation involves increased accumulation of intra-abdominal visceral adipose tissue and ectopic fat around internal organs such as the heart, blood vessels, liver, and kidneys that alter their functions. Other changes associated with aging include alterations in adipokine secretion and changes in adipocyte size and numbers. Aging adipocytes play a role in mediating chronic inflammation, metabolic dysfunction, and insulin resistance. Visceral adipose tissue, which increases in volume with aging, is in particular associated with inflammation, angiogenic dysfunction, and microvascular abnormalities, and mediators released by visceral fat may have adverse consequences systemically in multiple target organs, including the cardiovascular system. Understanding mechanisms underlying adipose tissue aging and its impact on cardiovascular health are important for developing interventions and treatments to promote healthy aging and reduce cardiometabolic disease risk.

FAM20C, a member of the family with sequence similarity 20, is involved in many physiological functions. Obesity, characterized by excessive accumulation of adipose tissue, has attracted more and more attention as a worldwide health problem. Here we generated adipocyte-specific FAM20C knockout mice to investigate the role of FAM20C in adipose tissue expansion and obesity. Our results demonstrate that knockout mice are protected against high fat diet-induced obesity, adiposity, and fatty liver disease. Additionally, knockout mice exhibited improved metabolic phenotypes, including enhanced glucose tolerance and insulin sensitivity compared with control mice. Furthermore, we observed reduced inflammatory infiltration and collagen deposition in the adipose tissues of knockout mice. Taken together, our results indicate that targeting FAM20C in adipocytes may be a promising strategy for the treatment of obesity and associated metabolic disorders.

Complex genetic and dietary cues contribute to the development of obesity, but how these are integrated on a molecular level is incompletely understood. Here, we show that PPARγ supports hypertrophic expansion of adipose tissue via transcriptional control of LPCAT3, a membrane-bound O-acyltransferase that enriches diet-derived omega-6 ( n -6) polyunsaturated fatty acids (PUFAs) in the phospholipidome. In high-fat diet-fed mice, lowering membrane n -6 PUFA levels by adipocyte-specific Lpcat3 knockout ( Lpcat3 AKO ) or by dietary lipid manipulation leads to dysfunctional triglyceride (TG) storage, ectopic fat deposition and insulin resistance. Aberrant lipolysis of stored TGs in Lpcat3 AKO adipose tissues instigates a non-canonical adaptive response that engages a futile lipid cycle to increase energy expenditure and limit further body weight gain. Mechanistically, we find that adipocyte LPCAT3 activity promotes TG storage by selectively enriching n -6 arachidonoyl-phosphatidylethanolamine at the ER-lipid droplet interface, which in turn favours the budding of large droplets that exhibit greater resistance to ATGL-dependent hydrolysis. Thus, our study highlights the PPARγ-LPCAT3 pathway as a molecular link between dietary n -6 PUFA intake, adipose expandability and systemic energy balance.

The metabolic syndrome (MetS) is a multiplex modifiable risk factor for cardiovascular disease, type 2 diabetes mellitus and other health outcomes, and is a major challenge to clinical practice and public health. The rising global prevalence of MetS, driven by urbanization, sedentary lifestyles and dietary changes, underlines the urgency of addressing this syndrome. We explore the complex underlying mechanisms, including genetic predisposition, insulin resistance, accumulation of dysfunctional adipose tissue and ectopic lipids in abdominal obesity, systemic inflammation and dyslipidaemia, and how they contribute to the clinical manifestations of MetS. Diagnostic approaches vary but commonly focus on abdominal obesity (assessed using waist circumference), hyperglycaemia, dyslipidaemia and hypertension, highlighting the need for population-specific and phenotype-specific diagnostic strategies. Management of MetS prioritizes lifestyle modifications, such as healthy dietary patterns, physical activity and management of excess visceral and ectopic adiposity, as foundational interventions. We also discuss emerging therapies, including new pharmacological treatments and surgical options, providing a forward-looking perspective on MetS research and care. This Primer aims to inform clinicians, researchers and policymakers about MetS complexities, advocating for a cohesive, patient-centred management and prevention strategy. Emphasizing the multifactorial nature of MetS, this Primer calls for integrated public health efforts, personalized care and innovative research to address this escalating health issue.

The progression of obesity involves several molecular mechanisms that are closely associated with the pathophysiological response of the disease. Endoplasmic reticulum (ER) stress is one such factor. Lipotoxicity disrupts endoplasmic reticulum homeostasis in the context of obesity. Furthermore, it induces ER stress by activating several signaling pathways via inflammatory responses and oxidative stress. ER performs crucial functions in protein synthesis and lipid metabolism; thus, triggers such as lipotoxicity can promote the accumulation of misfolded proteins in the organelle. The accumulation of these proteins can lead to metabolic disorders and chronic inflammation, resulting in cell death. Thus, alternatives, such as flavonoids, amino acids, and polyphenols that are associated with antioxidant and anti-inflammatory responses have been proposed to attenuate this response by modulating ER stress via the administration of nutrients and bioactive compounds. Decreasing inflammation and oxidative stress can reduce the expression of several ER stress markers and improve clinical outcomes through the management of obesity, including the control of body weight, visceral fat, and lipid accumulation. This review explores the metabolic changes resulting from ER stress and discusses the role of nutritional interventions in modulating the ER stress pathway in obesity.

The functional differences between preadipocytes and fully differentiated mature adipocytes derived from stromal vascular fraction stem cells, as well as primary adipocytes have been analysed by evaluating their response to the obesogenic factor (a saturated fatty acid) and TNF-triggered inflammation. The analysis of single adipocytes shows that the saturated fatty acid (palmitic acid) accumulation is accompanied by inflammation and considerably dependent on the stage of the adipogenesis. In particular, preadipocytes show the exceptional potential for palmitic acid uptake resulting in their hypertrophy and the elevated cellular expression of the inflammation marker (ICAM-1). Our research provides new information on the impact of obesogenic factors on preadipocytes that is important in the light of childhood obesity prevention.

Single-cell omics technologies that profile genes (genomic and epigenomic) and determine the abundance of mRNA (transcriptomic), protein (proteomic and secretomic), lipids (lipidomic), and extracellular matrix (matrisomic) support the dissection of adipose tissue heterogeneity at unprecedented resolution in a temporally and spatially defined manner. In particular, cell omics technologies may provide innovative biomarkers for the identification of rare specific progenitor cell subpopulations, assess transcriptional and proteomic changes affecting cell proliferation and immunomodulatory potential, and accurately define the lineage hierarchy and differentiation status of progenitor cells. Unraveling adipose tissue complexity may also provide for the precise assessment of a dysfunctional state, which has been associated with cancer, as cancer-associated adipocytes play an important role in shaping the tumor microenvironment supporting tumor progression and metastasis, obesity, metabolic syndrome, and type 2 diabetes mellitus. The information collected by single-cell omics has relevant implications for regenerative medicine because adipose tissue is an accessible source of multipotent cells; alternative cell-free approaches, including the use of adipose tissue stromal cell-conditioned medium, extracellular vesicles, or decellularized extracellular matrix, are clinically valid options. Subcutaneous white adipose tissue, which is generally harvested via liposuction, is highly heterogeneous because of intrinsic biological variability and extrinsic inconsistencies in the harvesting and processing procedures. The current limited understanding of adipose tissue heterogeneity impinges on the definition of quality standards appropriate for clinical translation, which requires consistency and uniformity of the administered product. We review the methods used for dissecting adipose tissue heterogeneity and provide an overview of advances in omics technology that may contribute to the exploration of heterogeneity and dynamics of adipose tissue at the single-cell level.