Insulin and iron availability stimulate and regulate erythropoiesis, respectively. The effects of hyperinsulinemia and/or iron overload on erythroid differentiation are unclear.

Male C57Bl/6J wild-type (WT) mice were fed a high-fat diet (HFD) (to produce hyperinsulinemia) or a control diet (CD) for varying periods (4-24 weeks). Hepcidin knock-out (Hamp1 -/- ) mice (which are iron-overloaded) were fed CD or HFD for 24 weeks. Terminal erythroid differentiation (TED) in the bone marrow (BM) from these mice was analyzed by flow cytometry. Hematological parameters were estimated in peripheral blood.

HFD-feeding of WT mice did not significantly affect erythroid precursors in the BM or hematological parameters. However, these mice had a significantly higher reticulocyte population in the BM than those fed CD (at all time points studied). Values of hematological parameters were higher in Hamp1 -/- mice than WT mice, at 24 weeks of feeding (irrespective of diet type), indicating increased erythropoiesis. Early erythroid precursors in the BM were higher in HFD-fed Hamp1 -/- mice than those fed CD.

HFD-feeding in WT mice resulted in increases in the proportion of reticulocytes in the bone marrow; maturation of the early erythroid precursors was not significantly affected. In Hamp1 -/- mice, HFD-feeding increased the number of early erythroid precursors.

Skeletal muscle alterations (SMAs) are being increasingly recognized in patients with metabolic dysfunction-associated steatotic liver disease (MASLD) and appear to be associated with deleterious outcomes in these patients. However, their actual prevalence and pathophysiology remain to be elucidated.

To determine the prevalence of SMAs and to assess the significance of circulating myokines as biomarkers in patients with MASLD.

Skeletal muscle strength and muscle mass were measured in a cross-sectional study in a cohort of 62 patients fulfilling MASLD criteria, recruited from the outpatient clinics of a tertiary level hospital. The degree of fibrosis and liver steatosis was studied using abdominal ultrasound and transitional elastography. Anthropometric and metabolic characteristics as well as serum levels of different myokines were also determined in the MASLD cohort. Statistical analysis was performed comparing results according to liver fibrosis and steatosis.

No significant differences were found in both skeletal muscle strength and skeletal muscle mass in patients with MASLD between different stages of liver fibrosis. Interestingly, serum levels of fibroblast growth factor-21 (FGF21) were significantly higher in patients with MASLD with advanced hepatic fibrosis (F3-F4) than in those with lower fibrosis stages (F0-F2) (197.49 ± 198.27 pg/mL vs 95.62 ± 83.67 pg/mL; P = 0.049). In addition, patients with MASLD with severe hepatosteatosis (S3) exhibited significantly higher serum levels of irisin (1116.87 ± 1161.86 pg/mL) than those with lower grades (S1-S2) (385.21 ± 375.98 pg/mL; P = 0.001).

SMAs were uncommon in the patients with MASLD studied. Higher serum levels of irisin and FGF21 were detected in patients with advanced liver steatosis and fibrosis, respectively, with potential implications as biomarkers.

Alterations of plasma lipoprotein levels and oxidative stress are frequently observed in obese patients, including low high-density lipoprotein (HDL) cholesterol (HDL-C) levels and alterations of HDL composition. Dysfunctional HDL with lower antioxidant and anti-inflammatory properties have also been demonstrated in obesity. There is increasing evidence that white adipose tissue (WAT) participates in several metabolic activities and modulates HDL-C levels and function. In obese subjects, the changes in morphology and function of adipose tissue lead to impaired regulatory function and are associated with a state of low-grade chronic inflammation, with increased release of pro-inflammatory adipokines and cytokines. These alterations may affect HDL metabolism and functions; thus, adipose tissue is considered a potential target for the prevention and treatment of obesity. A cornerstone of obesity prevention and therapy is lifestyle modification through dietary changes, which is reflected in the modulation of plasma lipoprotein metabolism. Some dietary components and metabolites directly affect the composition and structure of HDL and modulate its anti-inflammatory and vasoprotective properties. The aims of the review are to summarize the crosstalk between adipocytes and HDL dysfunction in human obesity and to highlight recent discoveries on beneficial dietary patterns as well as nutritional components on inflammation and HDL function in human obesity.

This study investigated the beneficial effects of Lactobacillus reuteri TISTR 2736 on glucose homeostasis, carbohydrate metabolism, and the underlying mechanisms of its actions in type 2 diabetic (T2D) rats.

A rat model of T2D was established by a combination of a high-fat diet and streptozotocin. The diabetic rats were treated daily with L. reuteri TISTR 2736 (2 × 108 CFU/day) for 30 days. Biochemical, histopathological, and molecular analyses were carried out to determine insulin signaling, carbohydrate metabolism, oxidative stress, and inflammation.

The results demonstrated that treatment with L. reuteri TISTR 2736 significantly ameliorated fasting blood glucose and glucose intolerance, and improved insulin sensitivity indices in the diabetic rats. The hepatic histopathology was improved with L. reuteri TISTR 2736 treatment, which was correlated with a reduction of hepatic lipid profiles. L. reuteri TISTR 2736 significantly reduced glycogen content, fructose 1,6-bisphosphatase activity, and phosphoenolpyruvate carboxykinase 1 protein expression, and enhanced hexokinase activity in the diabetic liver. The downregulation of IRS1 and phosphorylated IRS1Ser307 and upregulation of PI3K and phosphorylated AKTSer473 proteins in the liver were found in the L. reuteri TISTR 2736-treated diabetic group. Furthermore, it was able to suppress oxidative stress and inflammation in the diabetic rats, as demonstrated by decreased malondialdehyde and protein levels of NF-κB, IL-6 and TNF-α, but increased antioxidant enzyme activities of superoxide dismutase, catalase, and glutathione peroxidase.

By inhibiting oxidative and inflammatory stress, L. reuteri TISTR 2736 alleviated hyperglycemia and improved carbohydrate metabolism through activating IRS1/PI3K/AKT pathway in the T2D rats.

The prevalence of type 2 diabetes is increasing worldwide. Various molecular mechanisms have been proposed to interfere with the insulin signaling pathway. Recent advances in proteomics and genomics indicate that one such mechanism involves the post-transcriptional regulation of insulin signaling by microRNA (miRNA). These noncoding RNAs typically induce messenger RNA (mRNA) degradation or translational repression by interacting with the 3' untranslated region (3'UTR) of target mRNA. Dietary components and patterns, which can either enhance or impair the insulin signaling pathway, have been found to regulate miRNA expression in both in vitro and in vivo studies. This review provides an overview of the current knowledge of how dietary components influence the expression of miRNAs related to the control of the insulin signaling pathway and discusses the potential application of these findings in precision nutrition.

Type 2 diabetes mellitus is a complex metabolic disorder characterized by insulin resistance and, subsequently, decreased insulin secretion. This condition is closely linked to obesity, a major risk factor that boosts the development of chronic systemic inflammation, which, in turn, is recognized for its crucial role in the onset of insulin resistance. Under conditions of obesity, adipose tissue, particularly visceral fat, becomes an active endocrine organ that releases a wide range of pro-inflammatory mediators, including cytokines, chemokines, and adipokines. These mediators, along with cluster of differentiation (CD) markers, contribute to the maintenance of systemic low-grade inflammation, promote cellular signaling and facilitate the infiltration of inflammatory cells into tissues. Emerging studies have indicated the accumulation of a new cell population in the adipose tissue in these conditions, known as myeloid-derived suppressor cells (MDSCs). These cells possess the ability to suppress the immune system, impacting obesity-related chronic inflammation. Given the limited literature addressing the role of MDSCs in the context of type 2 diabetes, this article aims to explore the complex interaction between inflammation, obesity, and MDSC activity. Identifying and understanding the role of these immature cells is essential not only for improving the management of type 2 diabetes but also for the potential development of targeted therapeutic strategies aimed at both glycemic control and the reduction in associated inflammation.

We investigated the effects of ultraprocessed food (UPF) consumption on metabolic disorders (e.g., adiposity, metabolic associated steatotic liver disease [MASLD], and insulin resistance) in children and adolescents with obesity to improve dietary guidelines and public health strategies.

The dietary intake of 149 participants (aged 8-17 years) was assessed with food diaries. The NOVA classification system was used to classify food according to the degree of processing. Metabolic outcomes, including the fat mass index (FMI), hepatic fat percentage, and insulin resistance, were measured via dual-energy X-ray absorptiometry (DXA), magnetic resonance imaging proton density fat fraction (MRI-PDFF), and biochemical analysis, respectively.

Greater UPF consumption from baseline to the 6-month follow-up was significantly associated with increased insulin and decreased total cholesterol and LDL-cholesterol. UPF consumption was positively associated with the prevalence of MASLD (liver MRI-PDFF ≥ 5%; odds ratio T3 vs. T1 = 1.75; 95% confidence interval [CI] 1.03, 3.00), moderate-to-severe MASLD (liver MRI-PDFF ≥ 10%; OR T3 vs. T1 = 4.19; 95% CI 1.72, 10.22), and insulin resistance (OR T3 vs. T1 = 2.44; 95% CI 1.33, 4.48), after adjusting for covariates. A linear dose-response relationship was observed between UPF consumption and the odds of moderate-to-severe MASLD and insulin resistance.

Greater UPF consumption was strongly associated with MASLD and insulin resistance in children and adolescents with obesity, underscoring the importance of reducing UPF consumption through dietary guidelines and public health interventions to mitigate the risk of obesity-related metabolic conditions in young populations.

Background: Identifying β-cells dysregulation in type 2 diabetes mellitus (T2DM) is crucial. Weight fluctuations are frequently observed during diabetes treatment. However, the relationship between body composition changes and islet β-cell function in individuals with T2DM remains insufficiently investigated. Methods: This retrospective longitudinal study encompassed a cohort of 775 T2DM patients, who underwent body composition measuring using dual-energy X-ray absorptiometry (DEXA) and followed up for a median of 2.29 years. Key metrics included body mass index (BMI), fat mass index (FMI), trunk fat mass index (TFMI), muscle mass index (MMI), appendicular skeletal muscle mass index (ASMI), muscle/fat mass ratio (M/F), and the appendicular skeletal muscle mass/trunk fat mass ratio (A/T) were then categorized and grouped. Insulin, C-peptide, and glucose levels were assessed concurrently following a glucose load. β-cell function included insulin resistance (HOMA-IR), insulin sensitivity (Matsuda index (MI)), and insulin secretion evaluated by HOMA-β and C-peptidogenic index (CGI). Results: Although no significant changes in BMI were observed, patients with T2DM at readmission exhibited higher FMI, TFMI, and ASMI, as well as elevated levels of HOMA-IR, MI, and CGI compared to baseline measurements. And lower MI, higher levels of CGI, and HOMA-IR were observed in BMI increased group. Univariate correlation analysis revealed a negative association between changes in BMI (ΔBMI) and ΔMI, while positive associations were observed in both ΔHOMA-IR and ΔCGI. Among body composition indexes, ΔFMI exhibited the strongest correlation with ΔHOMA-IR (r = 0.255, p < 0.001), and ΔASMI was positively associated with ΔMI and ΔCGI (r = 0.131 and 0.194, respectively). Moreover, increased levels of BMI and FMI were associated with a greater risk of progressive insulin resistance compared to the decreased, whereas the trend was converse in ASMI and A/T. Conclusions: Increased FMI may partially contribute to the deterioration of insulin resistance, while increased ASMI is associated with improved insulin sensitivity and secretion. Maintaining an appropriate BMI and muscle/fat ratio is conductive to prevent the progression of insulin resistance in patients with T2DM.

Over the past few decades, the scientific community has been highly concerned about the obesity epidemic. Artificial sweeteners are compounds that mimic the sweet taste of sugar but have no calories or carbohydrates; hence, they are very popular among patients suffering from diabetes or obesity, aiming to achieve glycemic and/or weight control. There are four different types of sweeteners: artificial, natural, rare sugars, and polyols. Artificial and natural sweeteners are characterized as non-nutritional sweeteners (NNSs) since they do not contain calories. The extended use of sweeteners has been reported to have a favorable impact on body weight and glycemic control in patients with type 2 diabetes (T2DM) and on tooth decay prevention. However, there is concern regarding their side effects. Several studies have associated artificial sweeteners' consumption with the development of insulin resistance, nonalcoholic fatty liver disease (NAFLD), gastrointestinal symptoms, and certain types of cancer. The present review focuses on the description of different types of sweeteners and the benefits and possible deleterious effects of the chronic consumption of NNSs on children's health. Additionally, possible underlying mechanisms of the unfavorable effects of NNSs on human health are described.

The exploration of targeted therapy has proven to be a highly promising avenue in the realm of drug development research. The human body generates a substantial amount of free radicals during metabolic processes, and if not promptly eliminated, these free radicals can lead to oxidative stress, disrupting homeostasis and potentially contributing to chronic diseases and cancers. Before the development of contemporary medicine with synthetic pharmaceuticals and antioxidants, there was a long-standing practice of employing raw, natural ingredients to cure a variety of illnesses. This practice persisted even after the active antioxidant molecules were known. The ability of natural antioxidants to neutralise excess free radicals in the human body and so prevent and cure a wide range of illnesses. The term "natural antioxidant" refers to compounds derived from plants or other living organisms that have the ability to control the production of free radicals, scavenge them, stop free radical-mediated chain reactions, and prevent lipid peroxidation. These compounds have a strong potential to inhibit oxidative stress. Phytochemicals (antioxidants) derived from plants, such as polyphenols, carotenoids, vitamins, and others, are central to the discussion of natural antioxidants. Not only may these chemicals increase endogenous antioxidant defenses, affect communication cascades, and control gene expression, but they have also shown strong free radical scavenging properties. This study comprehensively summarizes the primary classes of natural antioxidants found in different plant and animal source that contribute to the prevention and treatment of diseases. Additionally, it outlines the research progress and outlines future development prospects. These discoveries not only establish a theoretical groundwork for pharmacological development but also present inventive ideas for addressing challenges in medical treatment.

Heart failure (HF), as the terminal manifestation of multiple cardiovascular diseases, causes a huge socioeconomic burden worldwide. Despite the advances in drugs and medical-assisted devices, the prognosis of HF remains poor. HF is well-accepted as a myriad of subcellular dys-synchrony related to detrimental structural and functional remodelling of cardiac components, including cardiomyocytes, fibroblasts, endothelial cells and macrophages. Through the covalent chemical process, post-translational modifications (PTMs) can coordinate protein functions, such as re-localizing cellular proteins, marking proteins for degradation, inducing interactions with other proteins and tuning enzyme activities, to participate in the progress of HF. Phosphorylation, acetylation, and ubiquitination predominate in the currently reported PTMs. In addition, advanced HF is commonly accompanied by metabolic remodelling including enhanced glycolysis. Thus, glycosylation induced by disturbed energy supply is also important. In this review, firstly, we addressed the main types of HF. Then, considering that PTMs are associated with subcellular locations, we summarized the leading regulation mechanisms in organelles of distinctive cell types of different types of HF, respectively. Subsequently, we outlined the aforementioned four PTMs of key proteins and signaling sites in HF. Finally, we discussed the perspectives of PTMs for potential therapeutic targets in HF.

Peroxidation of polyunsaturated fatty acids results in the creation of numerous α, β-unsaturated aldehydes, many of which are complicated by the development of diabetes. Trans, trans-2,4-decadienal (DDE) is a dietary α, β-unsaturated aldehyde that is commonly found in food and the environment. However, it is unknown whether DDE exposure has some negative effects on glucose homeostasis and insulin sensitivity. This study investigated the biological effects of long-term DDE exposure in normal chow diet (NCD)-fed non-obese mice and high-fat diet (HFD)-fed obese mice. Results showed that oral administration of DDE for 14 weeks did not cause severe toxicity in NCD-fed non-obese mice but had significant adverse effects in HFD-fed obese mice. It was found that DDE exposure caused significant increases in LDL and ALT levels and aggravated glucose intolerance and insulin resistance in obese mice. Moreover, DDE robustly accumulated in adipose tissue and promoted the impairment of the insulin signaling pathway in the adipose tissue of obese mice while not affecting the skeletal muscle or liver. Mechanistically, DDE aggravated adipose tissue inflammation by promoting M1 macrophage accumulation and increasing proinflammatory cytokines in the adipocytes of obese mice, thus leading to impaired systemic insulin resistance. These findings provide crucial insights into the potential health impacts of long-term DDE exposure.

Rising obesity and associated multi-systemic complications amplify the health burden. Euphorbia kansui (EK) extract is clinically recognized for managing obesity. In a human study, 240 obese individuals were categorized into two cohorts: those receiving solely herbal medicine (HM group) and those administered EK concomitantly with herbal medicine (EK group). An in vivo examination using C57BL/6-Lepob/Lepob mice elucidated mechanisms involving macrophages and gut microbiota with associated metabolic advantages. The clinical study revealed a significant 7.22% body weight reduction during 91.55 average treatment days and examined 16.71% weight loss at 300 days after treatment. In whole subjects, 60.4%, 21.3%, and 6.3% achieved weight reductions exceeding 5%, 10%, and 15%, respectively. Impressively, the EK group exhibited superior weight loss compared to the HM group (EK: -7.73% vs. HM: -6.27%, p = 0.012). The anti-obesity effect was positively associated with EK therapy frequency and herbal medicine duration. In the in vivo study, EK significantly improved insulin sensitivity and mitigated infiltration of adipose tissue macrophages (ATMs) by modulating the CD11c+ and CD206+ subtypes. EK also correlated with increased Bacteroidetes and Firmicutes populations and reduced Proteobacteria and Verrucomicrobia. Consequently, EK is an effective adjunctive anti-obesity therapy offering metabolic benefits by modulating ATMs and gut microbiota profiles.

Turmeric, derived from Curcuma longa, and Lactobacillus paracasei, a lactic acid bacteria, have been studied for their potential antiobesity effects. To date, the antiobesity effects of turmeric fermented with L. paracasei have not been sufficiently investigated. This study was conducted via oral administration of 5% L. paracasei-fermented (FT) and unfermented turmeric (UT) in diet over 16 weeks using high-fat diet (HFD)-induced obese C57BL/6J mice. Results showed that the curcuminoid content of turmeric decreased following fermentation. Furthermore, FT significantly suppressed weight gain and liver and visceral adipose tissue weight and reduced plasma metabolic parameters in both the UT and FT experimental groups. The effects of FT were more noticeable than those of the unfermented form. Moreover, FT downregulated the expression of adipogenesis, lipogenesis, and inflammatory-related protein, but upregulated liver β-oxidation protein SIRT 1, PPARα, and PGC-1α in perigonadal adipose tissue. Additionally, FT ameliorated insulin resistance by activating insulin receptor pathway protein expressions in visceral adipose tissues. FT also modulated gut microbiota composition, particularly in two beneficial bacteria, Akkermansia muciniphila and Desulfovibrio, as well as two short-chain fatty acid-producing bacteria: Muribaculum intestinale and Deltaproteobacteria. Our findings indicate that the modulation effect of FT may be an important pathway for its antiobesity mechanisms.

Obesity has reached global epidemic proportions, and even though its effects are well-documented, studying the interactions among all influencing factors is crucial for a better understanding of its physiopathology. In a high-fat-diet-induced obesity animal model using C57BL/6J mice, behavioural responses were assessed through a battery of tests, while stress biomarkers and systemic inflammatory cytokines were measured using an Enzyme-Linked ImmunoSorbent Assay and a Bio-Plex Multiplex System. The peritoneal macrophage microbicide capacity was analysed via flow cytometry, and crown-like structures (CLSs) in white adipose tissue (WAT) were evaluated through staining techniques. Results indicated that obese mice exhibited increased body weight, hyperglycaemia, and hyperlipidaemia after 18 weeks on a high-fat diet, as well as worse physical conditions, poorer coordination and balance, and anxiety-like behaviour. Differences in corticosterone and noradrenaline concentrations were also found in obese animals, revealing a stress response and noradrenergic dysregulation, along with a weakened innate immune response characterized by a lower microbicide capacity, and the presence of an underlying inflammation evidenced by more CLSs in WAT. Altogether, these findings indicate that obesity deteriorates the entire stress, inflammatory, metabolic, sensorimotor and anxiety-like behavioural axis. This demonstrates that jointly evaluating all these aspects allows for a deeper and better exploration of this disease and its associated comorbidities, emphasizing the need for individualized and context-specific strategies for its management.

Overweight, often known as obesity, is the abnormal and excessive accumulation of fat that exposes the health of a person at risk by increasing the likelihood that they may experience many chronic conditions. Consequently, obesity has become a global health threat, presenting serious health issues, and attracting a lot of attention in the healthcare profession and the scientific community.

This study aims to explore the anti-adipogenic properties of 7-MEGA™ in an attempt to address obesity, using both in vitro and in vivo research. The effects of 7MEGA™ at three distinct concentrations were investigated in obese mice who were given a high-fat diet (HFD) and 3T3-L1 adipocytes.

7MEGA™ decreased the total fat mass, overall body weight, and the perirenal and subcutaneous white adipose tissue (PWAT and SWAT) contents in HFD mice. Additionally, 7MEGA™ showed promise in improving the metabolic health of individuals with obesity and regulate the levels of insulin hormone, pro-inflammatory cytokines and adipokines. Furthermore, Peroxisome proliferator-activated receptors (PPAR) α and γ, Uncoupling Protein 1 (UCP-1), Sterol Regulatory Element-Binding Protein 1 (SREBP-1), Fatty Acid-Binding Protein 4 (FABP4), Fatty Acid Synthase (FAS), Acetyl-CoA Carboxylase (ACC), Stearoyl-CoA Desaturase-1 (SCD-1) and CCAAT/Enhancer-Binding Protein (C/EBPα) were among the adipogenic regulators that 7MEGA™ could regulate.

In summary, this study uncovered that 7MEGA™ demonstrates anti-adipogenic and anti-obesity effects, suggesting its potential in combating obesity.

Prepubertal obesity is growing at an alarming rate and is now considered a risk factor for renal injury. Recently, we reported that the early development of renal injury in obese Dahl salt-sensitive (SS) leptin receptor mutant (SS LepR mutant) rats was associated with increased T-cell infiltration and activation before puberty. Therefore, the current study investigated the effect of inhibiting T-cell activation with abatacept on the progression of renal injury in young obese SS LepR mutant rats before puberty. Four-week-old SS and SS LepR mutant rats were treated with IgG or abatacept (1 mg/kg; ip, every other day) for 4 weeks. Abatacept reduced the renal infiltration of T cells by almost 50% in SS LepR mutant rats. Treatment with abatacept decreased the renal expression of macrophage inflammatory protein-3 alpha while increasing IL-4 in SS LepR mutant rats without affecting SS rats. While not having an impact on blood glucose levels, abatacept reduced hyperinsulinemia and plasma triglycerides in SS LepR mutant rats without affecting SS rats. We did not observe any differences in the mean arterial pressure among the groups. Proteinuria was markedly higher in SS LepR mutant rats than in SS rats throughout the study, and treatment with abatacept decreased proteinuria by about 40% in SS LepR mutant rats without affecting SS rats. We observed significant increases in glomerular and tubular injury and renal fibrosis in SS LepR mutant rats versus SS rats, and chronic treatment with abatacept significantly reduced these renal abnormalities in SS LepR mutant rats. These data suggest that renal T-cell activation contributes to the early progression of renal injury associated with prepubertal obesity.

Obesity is a multi-factorial disease frequently associated with poor nutritional habits and linked to many detrimental health outcomes. Individuals with obesity are more likely to have increased levels of persistent inflammatory and metabolic dysregulation. The goal of this study was to compare four dietary patterns differentiated by macronutrient content in a postmenopausal model. Dietary patterns were high carbohydrate (HC), high fat (HF), high carbohydrate plus high fat (HCHF), and high protein (HP) with higher fiber.

Changes in body weight and glucose levels were measured in female, ovariectomized C57BL/6 mice after 15 weeks of feeding. One group of five mice fed the HCHF diet was crossed over to the HP diet on day 84, modeling a 21-day intervention. In a follow-up study comparing the HCHF versus HP dietary patterns, systemic changes in inflammation, using an 80-cytokine array and metabolism, by untargeted liquid chromatography-mass spectrometry (LCMS)-based metabolomics were evaluated.

Only the HF and HCHF diets resulted in obesity, shown by significant differences in body weights compared to the HP diet. Body weight gains during the two-diet follow-up study were consistent with the four-diet study. On Day 105 of the 4-diet study, glucose levels were significantly lower for mice fed the HP diet than for those fed the HC and HF diets. Mice switched from the HCHF to the HP diet lost an average of 3.7 grams by the end of the 21-day intervention, but this corresponded with decreased food consumption. The HCHF pattern resulted in dramatic inflammatory dysregulation, as all 80 cytokines were elevated significantly in the livers of these mice after 15 weeks of HCHF diet exposure. Comparatively, only 32 markers changed significantly on the HP diet (24 up, 8 down). Metabolic perturbations in several endogenous biological pathways were also observed based on macronutrient differences and revealed dysfunction in several nutritionally relevant biosynthetic pathways.

Overall, the HCHF diet promoted detrimental impacts and changes linked to several diseases, including arthritis or breast neoplasms. Identification of dietary pattern-specific impacts in this model provides a means to monitor the effects of disease risk and test interventions to prevent poor health outcomes through nutritional modification.

This study examined whey protein's impact on insulin resistance in a high-fat diet-induced pediatric obesity mouse model. Pregnant mice were fed high-fat diets, and male pups continued this diet until 8 weeks old, then were split into high-fat, whey, and casein diet groups. At 12 weeks old, their body weight, fasting blood glucose (FBG), blood insulin level (IRI), homeostatic model assessment for insulin resistance (HOMA-IR), liver lipid metabolism gene expression, and liver metabolites were compared. The whey group showed significantly lower body weight than the casein group at 12 weeks old (p = 0.034). FBG was lower in the whey group compared to the high-fat diet group (p < 0.01) and casein group (p = 0.058); IRI and HOMA-IR were reduced in the whey group compared to the casein group (p = 0.02, p < 0.01, p < 0.01, respectively). The levels of peroxisome proliferator-activated receptor α and hormone-sensitive lipase were upregulated in the whey group compared to the casein group (p < 0.01, p = 0.03). Metabolomic analysis revealed that the levels of taurine and glycine, both known for their anti-inflammatory and antioxidant properties, were upregulated in the whey group in the liver tissue (p < 0.01, p < 0.01). The intake of whey protein was found to improve insulin resistance in a high-fat diet-induced pediatric obesity mouse model.

The worldwide prevalence of obesity highlights the potential contribution of endocrine-disrupting chemicals (EDCs). However, common epidemiological measures such as body mass index and waist circumference may misrepresent the intricate obesity risks these chemicals pose across genders. This study delves deeper into abdominal fat by differentiating between subcutaneous and visceral regions by analyzing data from National Health and Nutrition Examination Surveys (NHANES). We particularly investigated the gender-specific associations between organophosphorus flame-retardant metabolites (mOPFRs), phthalates (mPAEs) and accumulated fat indexes from 2536 people. Aiding by Bayesian Kernel Machine Regression (BKMR), we found while co-exposure to mOPFRs and mPAEs was linked to general and abdominal obesity across the entire and gender-specific populations, a gender-specific fat distribution emerged. For women, urinary BDCPP and MBzP were linked to an increased subcutaneous fat index (SFI) [BDCPP OR: 1.12 (95% CI: 1.03-1.21), MBzP OR: 1.09 (95% CI: 1.01-1.18)], but not to visceral fat index (VFI). These metabolites had a combined linkage with SFI, with BDCPP (weighting 22.0%) and DPHP (weighting 31.0%) being the most influential in Quantile g-computation model (qgcomp) model. In men, BCEP exposure exclusively associated with the elevated VFI [OR: 1.14 (95% CI: 1.03-1.26)], a trend further highlighted in mixture models with BCEP as the predominant association. Intriguingly, only males displayed a marked correlation between these metabolites and insulin resistance in subpopulation. An attempted mediation analysis revealed that elevated C-reactive protein mediated 12.1% of the association between urinary BCEP and insulin resistance, suggesting a potential role of inflammation. In conclusion, the gender-specific fat distribution and insulin resistance that associated with mOPFRs represented the potential risk of these chemicals to man.

Background: WCFA19 (Weissella confusa WIKIM51), found during the fermentation of kimchi, is known for its inhibitory effects on body weight and body fat. This study looked at the impact of WCFA19 isolated from dandelion kimchi on weight loss in overweight and obese adults that are otherwise healthy. Methods: This study was conducted as a multicenter, double-blind, randomized, placebo-controlled study with 104 overweight and obese subjects. Subjects were randomized evenly into the test group (WCFA19, 500 mg, n = 40) or control group (n = 34) for 12 weeks from 14 June 2021 to 24 December 2021. Effects were based on DEXA to measure changes in body fat mass and percentage. Results: Among the 74 subjects analyzed, WCFA19 oral supplementation for 12 weeks resulted in a significant decrease in body fat mass of 633.38 ± 1396.17 g (p = 0.0066) in overweight and obese individuals in the experimental group. The control group showed an increase of 59.10 ± 1120.57 g (p = 0.7604), indicating a statistically significant difference between the two groups. There was also a statistically significant difference (p = 0.0448) in the change in body fat percentage, with a decrease of 0.41 ± 1.22% (p = 0.0424) in the experimental group and an increase of 0.17 ± 1.21% (p = 0.4078) in the control group. No significant adverse events were reported. Conclusions: Oral supplementation of 500 mg of WCFA19 for 12 weeks is associated with a decrease in body weight, particularly in body fat mass and percentage.

Obesity presents a significant global health challenge, increasing the susceptibility to chronic conditions such as diabetes, cardiovascular disease, and hypertension. Within the context of obesity, lipid metabolism, adipose tissue formation, and inflammation are intricately linked to endoplasmic reticulum stress (ERS). ERS modulates metabolism, insulin signaling, inflammation, as well as cell proliferation and death through the unfolded protein response (UPR) pathway. Serving as a crucial nexus, ERS bridges the functionality of adipose tissue and the inflammatory response. In this review, we comprehensively elucidate the mechanisms by which ERS impacts adipose tissue function and inflammation in obesity, aiming to offer insights into targeting ERS for ameliorating metabolic dysregulation in obesity-associated chronic diseases such as hyperlipidemia, hypertension, fatty liver, and type 2 diabetes.

Silymarin has ameliorated obesity, type 2 diabetes (T2DM), and insulin resistance (IR) in combination with standard therapy, diet, or exercise in recent studies. Obesity and IR are the main risk factors for developing T2DM and other metabolic disorders. Today, there is a need for new strategies to target IR in patients with these metabolic diseases. In the present longitudinal study, a group of non-diabetic insulin-resistant women with type 1 and type 2 obesity were given silymarin for 12 weeks, with no change in habitual diet and physical activity. We used the Homeostatic Model Assessment for Insulin Resistance Index (HOMA-IR) to determine IR at baseline and after silymarin treatment (t = 12 weeks). We obtained five timepoint oral glucose tolerance tests, and other biochemical and clinical parameters were analyzed before and after treatment. Treatment with silymarin alone significantly reduced mean fasting plasma glucose (FPG) and HOMA-IR levels at 12 weeks compared to baseline values (p < 0.05). Mean fasting plasma insulin (FPI), total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides (Tg), indirect bilirubin, and C-reactive protein (CRP) levels decreased compared to baseline values, although changes were non-significant. The overall results suggest that silymarin may offer a therapeutic alternative to improve IR in non-diabetic individuals with obesity. Further clinical trials are needed in this type of patient to strengthen the results of this study.

Observational studies have reported high comorbidity between obesity and severe COVID-19. The aim of this study is to explore whether genetic factors are involved in the co-occurrence of the two traits. Based on the available genome-wide association studies (GWAS) summary statistics, we explored the genetic correlation and performed cross-trait meta-analysis (CPASSOC) and colocalization analysis (COLOC) to detect pleiotropic single nucleotide polymorphisms (SNPs). At the genetic level, we obtained genes detected by Functional mapping and annotation (FUMA) and the Multi-marker Analysis of GenoMic Annotation (MAGMA). Potential functional genes were further investigated by summary-data-based Mendelian randomization (SMR). Finally, the casualty was identiied using the latent causal variable model (LCV). A significant positive genetic correlation was revealed between obesity and COVID-19. We found 331 shared genetic SNPs by CPASSOC and 13 shared risk loci by COLOC. At the genetic level, We obtained 3546 pleiotropic genes, among which 107 genes were found to be significantly expressed by SMR. Lastly, we observed these genes were mainly enriched in immune pathways and signaling transduction. These indings could provide new insights into the etiology of comorbidity and have implications for future therapeutic trial.

To discuss the impact of overactive bladder (OAB) on medical students. overactive bladder. is a chronic condition that causes sudden and intense urges to urinate, which can have significant physical and psychological effects on patients' lives. The prevalence of OAB among medical students is relatively high, with some studies reporting rates as high as 35.4%. This research aims to shed light on the prevalence rates and risk factors associated with OAB among medical students in Jordan.

A cross-sectional study was conducted using an online self-reported questionnaire as the study tool. The questionnaire collected the sociodemographic, health, and academic characteristics of medical students, as well as the new 7-item OABSS score.

Out of the total sample of medical students surveyed (n = 525), 44.5% reported experiencing symptoms of OAB. Furthermore, the analysis also revealed that there was a significant difference in the prevalence of OAB between the ages of medical students. In addition, the study also found that there was a significant association between OAB symptoms and basic years, positive history of diagnostic UTI, positive history of recent trauma, high stress, and taking certain medications.

The study highlights the need for further research in this area and emphasizes the possible implications of OAB for medical students, including the need for additional support and resources to manage the condition.

Type 2 diabetes mellitus (T2DM) is one of the most common chronic diseases employing abnormal levels of insulin. Enhancing the insulin production is greatly aided by the regulatory mechanisms of the Fractalkine receptor (CX3CR1) system in islet β-cell function. However, elements including a high-fat diet, obesity, and ageing negatively impact the expression of CX3CR1 in islets. CX3CL1/CX3CR1 receptor-ligand complex is now recognized as a novel therapeutic target. It suggests that T2DM-related β-cell dysfunction may result from lower amount of these proteins. We analyzed the differential expression of CX3CR1 gene samples taken from persons with T2DM using data obtained from the Gene Expression Omnibus database. Homology modeling enabled us to generate the three-dimensional structure of CX3CR1 and a possible binding pocket. The optimized CX3CR1 structure was subjected to rigorous screening against a massive library of 693 million drug-like molecules from the ZINC15 database. This screening process led to the identification of three compounds with strong binding affinity at the identified binding pocket of CX3CR1. To further evaluate the potential of these compounds, molecular dynamics simulations were conducted over a 50 ns time scale to assess the stability of the protein-ligand complexes. These simulations revealed that ZINC000032506419 emerged as the most promising drug-like compound among the three potent molecules. The discovery of ZINC000032506419 holds exciting promise as a potential therapeutic agent for T2D and other related metabolic disorders. These findings pave the way for the development of effective medications to address the complexities of T2DM and its associated metabolic diseases.

The global prevalence of diabetes mellitus is rising, especially in India. Medicinal herbs, whether used alone or in combination with conventional medicines, have shown promise in managing diabetes and improving overall well-being. Piperine (PIP), a major bioactive compound found in pepper, is gaining attention for its beneficial properties. This study aimed to assess whether PIP could alleviate diabetes by targeting insulin pathway-related molecules in the adipose tissue of rats on a high-fat diet (HFD). After 60 days on the HFD, rats received PIP at a dose of 40 mg/kg body weight for one month. The results showed that PIP significantly improved metabolic indicators, antioxidant enzymes, and carbohydrate metabolic enzymes. It also regulated the mRNA and protein expression of insulin signaling, which had been disrupted by the diet and sucrose intake. Molecular docking analysis also revealed strong binding of PIP to key diabetes-related regulatory proteins, including Akt (-6.2 kcal/mol), IR (-7.02 kcal/mol), IRS-1 (-6.86 kcal/mol), GLUT4 (-6.24 kcal/mol), AS160 (-6.28 kcal/mol), and β-arrestin (-6.01 kcal/mol). Hence, PIP may influence the regulation of glucose metabolism through effective interactions with these proteins, thereby controlling blood sugar levels due to its potent antilipidemic and antioxidant properties. In conclusion, our study provides in vivo experimental evidence against the HFD-induced T2DM model for the first time, making PIP a potential natural remedy to enhance the quality of life for diabetic patients and aid in their management.

Angiopoietin-like proteins (ANGPTLs) mediate many metabolic functions. We had recently reported increased plasma levels of ANGPTL8 in obese adults of Arab ethnicity. However, data on ANGPTL8 levels in adolescent obesity is lacking. Arab population is characterized by a rapid transition, due to sudden wealth seen in the post-oil era, in lifestyle, food habits and extent of physical activity. We adopted a cross-sectional study on Arab adolescents from Kuwait to examine the role of ANGPTL8 in adolescent obesity. The study cohort included 452 adolescents, aged 11-14 years, recruited from Middle Schools across Kuwait. BMI-for-age growth charts were used to categorize adolescents as normal-weight, overweight, and obese. ELISA and bead-based multiplexing assays were used to measure plasma levels of ANGPTL8 and other inflammation and obesity-related biomarkers. Data analysis showed significant differences in the plasma levels of ANGPTL8 among the three subgroups, with a significant increase in overweight and obese children compared to normal-weight children. This observation persisted even when the analysis was stratified by sex. Multinomial logistic regression analysis illustrated that adolescents with higher levels of ANGPTL8 were 7 times more likely to become obese and twice as likely to be overweight. ANGPTL8 levels were correlated with those of hsCRP, leptin and chemerin. ANGPTL8 level had a reasonable prognostic power for obesity with an AUC of 0.703 (95%-CI=0.648-0.759). These observations relating to increased ANGPTL8 levels corresponding to increased BMI-for-age z-scores indicate that ANGPTL8, along with hsCRP, leptin and chemerin, could play a role in the early stages of obesity development in children. ANGPTL8 is a potential early marker for adolescent obesity and is associated with well-known obesity and inflammatory markers.

Obesity is a multifactorial condition associated with metabolic alterations that can be aggravated during female aging. Calorie restriction via intermittent fasting (IF) diets may reduce body weight and therefore have the potential to decrease obesity and associated comorbidities, such as insulin resistance. This study investigated the effects of two IF protocols, alternate-day fasting (ADF) and time-restricted feeding (TRF) in middle-aged obese female rats.

Wistar rats (age 15 mo) were fed with standard chow or high-fat diet for 8 wk and then separated into the following groups (n = 5-8 each) for another 8 wk: control (received standard chow), obese (received high-fat diet), obese + ADF (24-h fasting protocol), and obese + TRF (14 h daily).

At the end of the study, both IF protocols were able to reduce body weight and body mass index compared with the obese group. However, no changes were observed in adiposity and glucose homeostasis. We also found an increase in total leukocytes, lymphocytes, and monocytes in the TRF group and a higher number of platelets in the ADF group. Blood lipid profiles, including triglycerides and high-density lipoprotein, as well as liver stress responses, such as heat shock protein 70 and malondialdehyde, were not changed by IF.

Although ADF and TRF protocols resulted in a reduction of body weight and body mass index, these dietary interventions did not promote health benefits, such as reducing blood lipid profile, adiposity, and insulin resistance. In addition, ADF and TRF increased inflammatory biomarkers, which may increase the risk of obesity-associated comorbidities.

Intermittent fasting (IF) is associated with enormous metabolic alterations that underpin its diverse health effects. Changes in lipid metabolism, particularly ceramides, and other sphingolipids, are among the most notable of these alterations. This study investigated the lipidomic alterations associated with 29-30 days of Ramadan diurnal intermittent fasting (RIF) in metabolically healthy overweight and obese subjects. A prospective cohort of 57 overweight and obese adults (70% males, 38.4 ± 11.2 years), with an age range of 18-58 years was observed prior to and at the conclusion of Ramadan. At both time points, anthropometric, biochemical (lipid profile, glycemic, and inflammatory markers), and dietary intake measurements were taken. Using liquid chromatography-mass spectrometry, a lipidomic analysis of ceramides and other sphingolipids was conducted. Using paired sample t-tests, pre- and post-Ramadan anthropometric, biochemical, and dietary values were compared. RIF was associated with improved levels of lipid profile compartments and inflammatory markers. In addition, RIF was associated with a decrease in plasma sphingosine and sphinganine, which was accompanied by a decrease in sphingosine 1-phosphate and sphinganine 1-phosphate. In addition, RIF was associated with decreased C17, C22, and C24 sphingomyelin, but not C14, C16, C18, C20, and C24:1 sphingomyelin, as well as C20, C22, C24, and C24:1 dihydrosphingomyelin, but not C16 and C18 dihydrosphingomyelin. This study demonstrates that RIF is associated with improvements in plasma sphingosine, sphinganine sphingomyelin, and dihydrosphingomyelin lipid species, as well as improved lipid profile and inflammatory markers, which may confer short-term protection against cardiometabolic problems in patients with overweight/obesity.

A high body mass index (BMI) can indicate overweight or obesity and is a crucial risk factor for breast cancer survivors. However, the association between high BMI and prognosis in early-stage breast cancer (EBC) remains unclear. We aimed to assess the effects of high BMI on the prognosis of patients with EBC.

The PubMed, Embase, and Cochrane Library databases and proceedings of major oncological conferences related to the effects of BMI on the prognosis of breast cancer were searched up to November 2021. Fixed- and random-effects models were used for meta-analyses. Pooled hazard ratios (HRs) and 95% confidence intervals (CIs) for disease-free survival (DFS) and overall survival (OS) were extracted from the included literature.

Twenty retrospective cohort studies with 33,836 patients with EBC were included. Overweight patients had worse DFS (HR: 1.16, 95% CI: 1.05-1.27, P = 0.002) and OS (HR: 1.20; 95% CI: 1.09-1.33, P < 0.001). Obesity also had adverse effects on DFS (HR: 1.17, 95% CI: 1.07-1.29, P = 0.001) and OS (HR: 1.30, 95% CI: 1.17-1.45, P < 0.001). Likewise, patients with high BMI had worse DFS (HR: 1.16, 95% CI: 1.08-1.26, P < 0.001) and OS (HR: 1.25, 95% CI: 1.14-1.39, P < 0.001). In subgroup analyses, overweight had adverse effects on DFS (HR: 1.11, 95% CI: 1.04-1.18, P = 0.001) and OS (HR: 1.18, 95% CI: 1.11-1.26, P < 0.001) in multivariate analyses, whereas the relationship that overweight had negative effects on DFS (HR: 1.21, 95% CI: 0.99-1.48, P = 0.058) and OS (HR: 1.39, 95% CI: 0.92-2.10, P = 0.123) was not statistically significant in univariate analysis. By contrast, obesity had adverse effects on DFS (HR: 1.21, 95% CI: 1.06-1.38, P = 0.004 and HR: 1.14, 95% CI: 1.08-1.22, P < 0.001) and OS (HR: 1.33, 95% CI: 1.15-1.54, P < 0.001 and HR: 1.23, 95% CI: 1.15-1.31, P < 0.001) in univariate and multivariate analyses, respectively.

Compared with normal weight, increased body weight (overweight, obesity, and high BMI) led to worse DFS and OS in patients with EBC. Once validated, these results should be considered in the development of prevention programs.

Sugar substitutes have been recommended to be used for weight and glycemic control. However, numerous studies indicate that consumption of artificial sweeteners exerts adverse effects on glycemic homeostasis. Although sucralose is among the most extensively utilized sweeteners in food products, the effects and detailed mechanisms of sucralose on insulin sensitivity remain ambiguous. In this study, we found that bolus administration of sucralose by oral gavage enhanced insulin secretion to decrease plasma glucose levels in mice. In addition, mice were randomly allocated into three groups, chow diet, high-fat diet (HFD), and HFD supplemented with sucralose (HFSUC), to investigate the effects of long-term consumption of sucralose on glucose homeostasis. In contrast to the effects of sucralose with bolus administration, the supplement of sucralose augmented HFD-induced insulin resistance and glucose intolerance, determined by glucose and insulin tolerance tests. In addition, we found that administration of extracellular signal-regulated kinase (ERK)-1/2 inhibitor reversed the effects of sucralose on glucose intolerance and insulin resistance in mice. Moreover, blockade of taste receptor type 1 member 3 (T1R3) by lactisole or pretreatment of endoplasmic reticulum stress inhibitors diminished sucralose-induced insulin resistance in HepG2 cells. Taken together, sucralose augmented HFD-induced insulin resistance in mice, and interrupted insulin signals through a T1R3-ERK1/2-dependent pathway in the liver.

Many diseases and degenerative processes affecting the nervous system and peripheral organs trigger the activation of inflammatory cascades. Inflammation can be triggered by different environmental conditions or risk factors, including drug and food addiction, stress, and aging, among others. Several pieces of evidence show that the modern lifestyle and, more recently, the confinement associated with the COVID-19 pandemic have contributed to increasing the incidence of addictive and neuropsychiatric disorders, plus cardiometabolic diseases. Here, we gather evidence on how some of these risk factors are implicated in activating central and peripheral inflammation contributing to some neuropathologies and behaviors associated with poor health. We discuss the current understanding of the cellular and molecular mechanisms involved in the generation of inflammation and how these processes occur in different cells and tissues to promote ill health and diseases. Concomitantly, we discuss how some pathology-associated and addictive behaviors contribute to worsening these inflammation mechanisms, leading to a vicious cycle that promotes disease progression. Finally, we list some drugs targeting inflammation-related pathways that may have beneficial effects on the pathological processes associated with addictive, mental, and cardiometabolic illnesses.

An increasing population of people, especially young adults who exercise, consume high protein diets along with carbonated drinks. While there are numerous studies on the effect of high protein diets, there is a need to understand how protein diets in combination with carbonated drinks impact physiology. In order to assess these effects on wistar rats' phenotype, antioxidants and inflammatory profiles, 64 wistar rats were divided into dietary groups of 8 male and 8 female animals each. The animals were fed standard diet as control (chow), chow and carbonated soda, a high protein diet (48.1% energy from protein) and a high protein diet with carbonated soda according to their groups. Body measurements, blood glucose levels, serum insulin levels, lipid peroxidation, antioxidant activity, adipokines and inflammatory markers concentrations were all determined. At the end of the study, body measurements, inflammatory markers and adipokine concentration were increased in animals fed the high protein diet and high protein-soda diet. There was a decrease in antioxidant and lipid peroxidation levels in protein fed male and female animals but those fed protein in combination with soda had increased lipid peroxidation levels. In conclusion, high protein diet in combination with carbonated soda impacts physiology differently from a high protein diet alone, and may stimulate weight gain, oxidative stress and HPD-related inflammation in Wistar rats.

Obesity is a metabolic disease that is caused by a lack of physical activity and is associated with an increased risk of chronic inflammation. A total of 40 obese adolescent females with an average age of 21.93 ± 1.35 years and average body mass index (BMI) of 30.81 ± 3.54 kg/m² were enrolled in this study, randomized, and divided into four groups, i.e., control (CTL; n = 10), moderate intensity aerobic training (MAT; n = 10), moderate intensity resistance training (MRT; n = 10), and moderate intensity combined aerobic-resistance training (MCT; n = 10). The enzyme-linked immunosorbent assay (ELISA) kits method was used to analyze the adiponectin and leptin levels between pre-intervention and post-intervention. Statistical analysis was conducted using a paired sample t-test, while correlation analysis between variables used the Pearson product-moment correlation test. Research data showed that MAT, MRT, and MCT significantly increased adiponectin levels and decreased leptin levels compared to the CTL (p ≤ 0.05). The results of the correlation analysis of delta (∆) data showed that an increase in adiponectin levels was significantly negatively correlated with a decrease in body weight (BW) (r = -0.671, p ≤ 0.001), BMI (r = -0.665, p ≤ 0.001), and fat mass (FM) (r = -0.694, p ≤ 0.001) and positively correlated with an increase in skeletal muscle mass (SMM) (r = 0.693, p ≤ 0.001). Whereas, a decrease in leptin levels was significantly positively correlated with a decrease in BW (r = 0.744, p ≤ 0.001), BMI (r = 0.744, p ≤ 0.001), and FM (r = 0.718, p ≤ 0.001) and negatively correlated with an increase in SMM (r = -0.743, p ≤ 0.001). In summary, it can be concluded that our data show that adiponectin levels increased and leptin levels decreased after the intervention of aerobic, resistance, and combined aerobic-resistance training.

Obesity has been associated with oxidative stress. Obese patients are at increased risk for diabetic cognitive dysfunction, indicating a pathological link between obesity, oxidative stress, and diabetic cognitive dysfunction. Obesity can induce the biological process of oxidative stress by disrupting the adipose microenvironment (adipocytes, macrophages), mediating low-grade chronic inflammation, and mitochondrial dysfunction (mitochondrial division, fusion). Furthermore, oxidative stress can be implicated in insulin resistance, inflammation in neural tissues, and lipid metabolism disorders, affecting cognitive dysfunction in diabetics.

High-sugar diet-induced prediabetes and obesity are a global current problem that can be the result of glucose or fructose. However, a head-to-head comparison between both sugars on health impact is still lacking, and Lactiplantibacillus plantarum dfa1 has never been tested, and has recently been isolated from healthy volunteers. The mice were administered with the high glucose or fructose preparation in standard mouse chaw with or without L. plantarum dfa1 gavage, on alternate days, and in vitro experiments were performed using enterocyte cell lines (Caco2) and hepatocytes (HepG2). After 12 weeks of experiments, both glucose and fructose induced a similar severity of obesity (weight gain, lipid profiles, and fat deposition at several sites) and prediabetes condition (fasting glucose, insulin, oral glucose tolerance test, and Homeostatic Model Assessment for Insulin Resistance (HOMA score)). However, fructose administration induced more severe liver damage (serum alanine transaminase, liver weight, histology score, fat components, and oxidative stress) than the glucose group, while glucose caused more prominent intestinal permeability damage (FITC-dextran assay) and serum cytokines (TNF-α, IL-6, and IL-10) compared to the fructose group. Interestingly, all of these parameters were attenuated by L. plantarum dfa1 administration. Because there was a subtle change in the analysis of the fecal microbiome of mice with glucose or fructose administration compared to control mice, the probiotics altered only some microbiome parameters (Chao1 and Lactobacilli abundance). For in vitro experiments, glucose induced more damage to high-dose lipopolysaccharide (LPS) (1 µg/mL) to enterocytes (Caco2 cell) than fructose, as indicated by transepithelial electrical resistance (TEER), supernatant cytokines (TNF-α and IL-8), and glycolysis capacity (by extracellular flux analysis). Meanwhile, both glucose and fructose similarly facilitated LPS injury in hepatocytes (HepG2 cell) as evaluated by supernatant cytokines (TNF-α, IL-6, and IL-10) and extracellular flux analysis. In conclusion, glucose possibly induced a more severe intestinal injury (perhaps due to LPS-glucose synergy) and fructose caused a more prominent liver injury (possibly due to liver fructose metabolism), despite a similar effect on obesity and prediabetes. Prevention of obesity and prediabetes with probiotics was encouraged.