Adipocyte Hypertrophy Research Articles

Adipokine Modulation in Endometrial Hyperplasia by Polyunsaturated Fatty Acids

Background Obesity is associated with a higher prevalence of endometrial hyperplasia, thereby increasing the risk of endometrial and ovarian cancers. The precise mechanisms linking obesity to endometrial hyperplasia remain unclear, but dysregulation of adipose tissue homeostasis is known to play a significant role. Hypertrophied adipocytes in obese individuals secrete various bioactive substances, including cytokines, growth factors, hormones, and metabolites. Additionally, hyperplastic adipocytes exhibit enhanced aromatase activity, leading to increased estrogen synthesis, which further promotes the development of endometrial hyperplasia. Purpose The purpose of this study is to explore the anti-inflammatory and anti-proliferative activities of the poly unsaturated fatty acids. Methodology An extensive literature survey has been performed to identify the role of adipokines and elevated endogenous estrogen levels in activating cell survival signaling pathways, such as PI3K/Akt/mTOR, MEK/ERK1, and JAK–STAT in endometrial cells and their possible role in Endometrial Hyperplasia. Further, the possible beneficial anti-inflammatory and anti-proliferative effects of polyunsaturated fatty acids (PUFAs) such as eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and arachidonic acid (AA) were explored. Results Numerous studies suggest the beneficial role of dietary fats, such as EPA, DHA, and AA in modulating the growth of endometrium in obesity-induced endometrial hyperplasia. PUFAs can activate adenosine monophosphate-activated protein kinase (AMPK), which inhibits gluconeogenesis and lipogenesis. It also phosphorylates acetyl-CoA, leading to a decrease in malonyl-CoA, which inhibits mitochondrial CPT1. Additionally, AMPK activation promotes β-oxidation, and PPAR-γ mechanisms by down regulating the NF-kB pathway involved in endometrial hyperplasia. Conclusion This review sheds light on the potential of PUFAs in mitigating estrogen synthesis, adipokine secretion, and endogenous aromatase activity in obesity induced endometrial hyperplasia. Furthermore, it critically evaluates the role and mechanisms of PUFAs in attenuating obesity-associated endometrial hyperplasia and reducing the risk of ovarian cancer.

CTRP9 alleviates diet induced obesity through increasing lipolysis mediated by enhancing autophagy-initiation complex formation.

Recently, emerging evidence has suggested that obesity become a prevalent health threat worldwide. Reportedly, CTRP9 can ameliorate HFD induced obesity. However, the molecular mechanism underlying the role of CTRP9 in obesity remains elusive. In this study, we reported its major function in the regulation of lipolysis. First, we found that the expression of CTRP9 was decreased in mature adipocytes and white adipose tissue of obese mice. Then, we showed that overexpression adipose tissue CTRP9 alleviated diet-induced obesity and adipocytes hypertrophy, improved glucose intolerance and raised energy expenditure. Moreover, CTRP9 increased the lipolysis in vitro and vivo. Additionally, we determined that CTRP9 enhanced autophagy flux in adipocytes. Intriguingly, knock down Beclin1 by SiRNA abolished the effect of CTRP9 on lipolysis. Mechanically, CTRP9 enhanced the expression of SNX26. We demonstrated that SNX26 was a component of the ATG14L-Beclin1-VPS34 complex and enhanced the assembly of the autophagy-initiation complex. Collectively, our results suggested that CTRP9 alleviated diet induced obesity through enhancing lipolysis mediated by autophagy-initiation complex formation.

Red Oranges and Olive Leaf Waste-Derived Bioactive Extracts Promote Adipocyte Functionality In Vitro.

Obesity is increasingly prevalent worldwide and is linked to metabolic diseases, such as insulin resistance (IR) and type 2 diabetes mellitus (T2DM), due to excessive free fatty acids (FFAs). Although lifestyle changes are effective, they often prove to be insufficient as initial treatments for obesity. Additionally, while surgical and pharmacological interventions are available, they are not entirely safe or effective. Recently, interest has grown in utilizing food waste and plant-derived phenolic compounds for their health benefits, presenting a promising avenue for managing obesity and its related disorders. Indeed, many studies have examined the potential inhibitory effects of the natural extract on adipocyte differentiation and lipid accumulation. This study focused on the evaluation of the effects of standardized extracts obtained from red oranges and olive leaf waste on 3T3-L1 murine pre-adipocyte and adipocyte functionality. Red orange extract (ROE) and olive leaf extract (OLE), alone and in combination, were tested to assess their anti-obesity and anti-inflammatory effects, as well as their potential therapeutic benefits. Three in vitro models were established to investigate the effects of the extracts on (I) adipocyte differentiation; (II) mature and hypertrophic adipocytes challenged with palmitic acid (PA) and erastin (ER), respectively; and (III) erastin-induced cytotoxicity on pre-adipocytes.

Modulation of gut microbiota by crude gac aril polysaccharides ameliorates diet-induced obesity and metabolic disorders

Obesity is a global health challenge that causes metabolic dysregulation and increases the risk of various chronic diseases. The gut microbiome is crucial in modulating host energy metabolism, immunity, and inflammation and is influenced by dietary factors. Gac fruit (Momordica cochinchinensis), widely consumed in Southeast Asia, has been proven to have various biological activities. However, the composition and effect of crude gac aril polysaccharides (GAP) on obesity and gut microbiota disturbed by high-fat diet (HFD) remain to be elucidated. Compositional analysis showed that GAP contains high oligosaccharides, with an average of 7–8 saccharide units. To mimic clinical obesity, mice were first made obese by feeding HFD for eight weeks. GAP intervention was performed from week 9 to week 20 in HFD-fed mice. Our results showed that GAP inhibited body weight gain, eWAT adipocyte hypertrophy, adipokine derangement, and hyperlipidemia in HFD-induced obese mice. GAP improved insulin sensitivity, impaired glucose tolerance, and hepatic steatosis. GAP modulated the gut microbiota composition and reversed the HFD-induced dysbiosis of at least 20 genera. Taken together, GAP improves metabolic health and modulates the gut microbiome to relieve obesity risk factors, demonstrating the potential of dietary GAP for treating obesity-associated disorders.

Preliminary Single-Cell RNA-Sequencing Analysis Uncovers Adipocyte Heterogeneity in Lipedema.

Background: Despite its increasing incidence and prevalence throughout Western countries, lipedema continues to be a very enigmatic disease, often misunderstood or misdiagnosed by the medical community and with an intrinsic pathology that is difficult to trace. The nature of lipedemic tissue is one of hypertrophic adipocytes and poor tissue turnover. So far, there are no identified pathways responsible, and little is known about the cell populations of lipedemic fat. Methods: Adipose tissue samples were collected from affected areas of both lipedema and healthy participants. For single-cell RNA sequencing analysis, the samples were dissociated into single-cell suspensions using enzymatic digestion and then encapsulated into nanoliter-sized droplets containing barcoded beads. Within each droplet, cellular mRNA was converted into complementary DNA. Complementary DNA molecules were then amplified for downstream analysis. Results: The single-cell RNA-sequencing analysis revealed three distinct adipocyte populations at play in lipedema. These populations have unique gene signatures which can be characterized as a lipid generating adipocyte, a disease catalyst adipocyte, and a lipedemic adipocyte. Conclusions: The single-cell RNA sequencing of lipedemic tissue samples highlights a triad of distinct adipocyte subpopulations, each characterized by unique gene signatures and functional roles. The interplay between these adipocyte subtypes offers promising insights into the complex pathophysiology of lipedema.

Loss-of-function G6PD variant moderated high-fat diet-induced obesity, adipocyte hypertrophy, and fatty liver in male rats

Obesity is a major risk factor for liver and cardiovascular diseases. However, obesity-driven mechanisms that contribute to the pathogenesis of multiple organ diseases are still obscure and treatment is inadequate. We hypothesized that increased glucose-6-phosphate dehydrogenase (G6PD), the key rate-limiting enzyme in the pentose shunt, is critical in evoking metabolic reprogramming in multiple organs and is a significant contributor to the pathogenesis of liver and cardiovascular diseases. G6PD is induced by carbohydrate-rich diet and insulin. Long-term (8 months) high-fat diet (HFD) feeding increased body weight and elicited metabolic reprogramming in visceral fat, liver, and aorta, of the wild-type rats. In addition, HFD increased inflammatory chemokines in visceral fat. Interestingly, CRISPR-edited loss-of-function Mediterranean G6PD variant (G6PDS188F) rats, which mimic human polymorphism, moderated HFD-induced weight gain and metabolic reprogramming in visceral fat, liver, and aorta. The G6PDS188F variant prevented HFD-induced CCL7 and adipocyte hypertrophy. Furthermore, the G6PDS188F variant increased Magel2 – a gene encoding circadian clock-related protein that suppresses obesity associated with Prader-Willi syndrome – and reduced HFD-induced non-alcoholic fatty liver. Additionally, the G6PDS188F variant reduced aging-induced aortic stiffening. Our findings suggest G6PD is a regulator of HFD-induced obesity, adipocyte hypertrophy, and fatty liver.

Effects of the composition of food and medicine homologous ingredients complex supplementation on lipid metabolism and gut microbiota diversity in high‐fat diet‐induced obese mice

SummaryDietary patterns are closely related to obesity, and a balanced diet can prevent obesity more than a single food or nutrient. In this study, we investigated the anti‐obesity effects of food and medicine homologous ingredient complex (FMHIC). The serum biochemical indices related to lipid metabolism were significantly improved in the FMHIC group. Meanwhile, it significantly inhibited the accumulation of lipid droplets, improved adipocyte hypertrophy and downregulated gene expression related to lipid production. FMHIC can effectively regulate intestinal flora richness and structural disorder in obese mice and result in a higher abundance of NK4A214_group and Prevotellaceae _UCG_001, and a lower abundance of Negativibacillus, Lachnospiraceae_NK4A136_group, Lachnoclostridium and GCA_900066575. Spearman correlation analysis showed that there was a strong correlation between species richness and lipid metabolism and that FMHIC might adjust lipid metabolism by regulating the abundance of intestinal flora. In conclusion, FMHIC regulates lipid metabolism and modulates gut microbiota to regulate high‐fat diet‐induced dysbiosis.

Hippo-YAP/TAZ-ROS signaling axis regulates metaflammation induced by SelenoM deficiency in high-fat diet-derived obesity

IntroductionMetabolic inflammation (metaflammation) in obesity is primarily initiated by proinflammatory macrophage infiltration into adipose tissue. SelenoM contributes to the modulation of antioxidative stress and inflammation in multiple pathological processes; however, its roles in metaflammation and the proinflammatory macrophage (M1)-like state in adipose tissue have not been determined. ObjectivesWe hypothesize that SelenoM could effectively regulate metaflammation via the Hippo-YAP/TAZ-ROS signaling axis in obesity derived from a high-fat diet. MethodsMorphological changes in adipose tissue were examined by hematoxylin-eosin (H&E) staining and fluorescence microscopy. The glucose tolerance test (GTT) and insulin tolerance test (ITT) were used to evaluate the impact of SelenoM deficiency on blood glucose levels. RNA-Seq analysis, LC-MS analysis, Mass spectrometry analysis and western blotting were performed to detect the levels of genes and proteins related to glycolipid metabolism in adipose tissue. ResultsHerein, we evaluated the inflammatory features and metabolic microenvironment of mice with SelenoM-deficient adipose tissues by multi-omics analyses. The deletion of SelenoM resulted in glycolipid metabolic disturbances and insulin resistance, thereby accelerating weight gain, adiposity, and hyperglycemia. Mice lacking SelenoM in white adipocytes developed severe adipocyte hypertrophy via impaired lipolysis. SelenoM deficiency aggravated the generation of ROS by reducing equivalents (NADPH and glutathione) in adipocytes, thereby promoting inflammatory cytokine production and the M1-proinflammatory reaction, which was related to a change in nuclear factor kappa-B (NF-κB) levels in macrophages. Mechanistically, SelenoM deficiency promoted metaflammation via Hippo-YAP/TAZ-ROS-mediated transcriptional regulation by targeting large tumor suppressor 2 (LATS2). Moreover, supplementation with N-acetyl cysteine (NAC) to reduce excessive oxidative stress partially rescued adipocyte inflammatory responses and macrophage M1 activation. ConclusionOur data indicate that SelenoM ameliorates metaflammation mainly via the Hippo-YAP/TAZ-ROS signaling axis in obesity. The identification of SelenoM as a key regulator of metaflammation presents opportunities for the development of novel therapeutic interventions targeting adipose tissue dysfunction in obesity.

Consumption of interesterified palm oil leads inflammation of white adipose tissue and triggers metabolic disturbances in mice on a high-fat diet

Growing obesity is linked to shifts in dietary patterns, particularly the increased intake of ultra-processed high-fat foods. This study aimed to evaluate the effects of interesterified palm oil consumption on glucose homeostasis, adipose tissue remodeling, and hepatic lipogenesis in C57BL/6 mice fed a high-fat diet. Sixty C57BL/6 mice were divided into four groups (n = 15): the control group (C) fed a standard diet (4% soybean oil), the high-fat group (HF) (23.8% lard), the high palm oil fat group (HFP) (23.8% palm oil), and the high interesterified palm fat group (HFI) (23.8% interesterified palm oil) for 8 weeks (all groups received 50% energy from lipids). The HFI group exhibited higher body mass than the HF group (+ 11%, P < 0.05), which was attributed to an increased percentage of fat mass. Plasma concentrations of IL-6, insulin, and HOMA-IR were also elevated in the HFI group. Both the HFP and HFI groups showed hypertrophied adipocytes and pancreatic islets, increased alpha and beta cell masses, hepatic steatosis, low expression of genes related to beta-oxidation, and upregulated lipogenesis. In conclusion, the consumption of interesterified palm oil alters inflammatory and glucose profiles.

Elderly Women Have a Higher Survival Rate of Grafted Donor Fat than Do Young Women Under the Influence of Low Estrogen Conditions.

Fat grafting is widely used in breast reconstruction and aesthetic plastic surgery. However, the success rate and effects of fat grafting, especially in elderly female donors, are observed. This study aimed to explore the difference in the survival rate of donor fat from elderly women and young women in fat grafting. We collected adipose tissue samples from two healthy Chinese women: a young woman and an elderly woman. In addition, adipose tissue samples were collected from female nude mice in four experimental groups-CON-Y, CON-O, OVX-Y, and OVX-O-after fat transplantation. Grafts were harvested, weighed, and subjected to assessment of histology and angiogenesis. An ovariectomy model was successfully established to validate the effect of low estrogen levels on fat grafting results. Due to the influence of low estrogen levels, the graft survival rate of donor site fat was significantly higher in elderly women than in young women, accompanied by a lesser degree of angiogenesis. Low estrogen levels led to adipocyte hypertrophy, which may be related to decreased AQP-7 expression. AQP-7 downregulation due to low estrogen levels induces adipocyte hypertrophy, and donor fat from elderly women exhibits a higher survival rate after fat transplantation. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Efficacy of Probiotic Strains Lactobacillus sakei Probio65 and Lactobacillus plantarum Probio-093 in Management of Obesity: An In Vitro and In Vivo Analysis.

The prevalence of obesity, characterized by an excessive accumulation of adipose tissue and adipocyte hypertrophy, presents a major public health challenge. This study investigates the therapeutic potential of two probiotic strains, Lactobacillus sakei Probio65 and Lactobacillus plantarum Probio-093, in the context of obesity. Utilizing 3T3-L1 cell-derived human adipocytes, we assessed Probio65's and Probio-093's capacity to mitigate triglyceride accumulation and influence adipocytokine production in vitro. Subsequently, an in vivo trial with male C57BL/6J mice examined the effects of both probiotic strains on adipose tissue characteristics, body weight, fat mass, and obesity-related gene expression. This study employed both live and ethanol-extracted bacterial cells. The results demonstrated significant reductions in the triglyceride deposition, body weight, and adipose tissue mass in the treated groups (p < 0.05). Furthermore, both strains modulated adipokine profiles by downregulating proinflammatory markers such as PAI-1, leptin, TNF-α, STAMP2, F4/80, resistin, and MCP-1, and upregulating the insulin-sensitive transporter GLUT4 and the anti-inflammatory adiponectin (p < 0.05). Our findings suggest that Lactobacillus sakei Probio65 and Lactobacillus plantarum Probio-093 are promising agents for microbiome-targeted anti-obesity therapies, offering the effective mitigation of obesity and improvement in adipocyte function in a murine model.

Investigating GABA Neuron-Specific Androgen Receptor Knockout in two Hyperandrogenic Models of PCOS.

Androgen excess is a hallmark feature of polycystic ovary syndrome (PCOS), the most common form of anovulatory infertility. Clinical and preclinical evidence links developmental or chronic exposure to hyperandrogenism with programming and evoking the reproductive and metabolic traits of PCOS. While critical androgen targets remain to be determined, central GABAergic neurons are postulated to be involved. Here, we tested the hypothesis that androgen signaling in GABAergic neurons is critical in PCOS pathogenesis in 2 well-characterized hyperandrogenic mouse models of PCOS. Using cre-lox transgenics, GABA-specific androgen receptor knockout (GABARKO) mice were generated and exposed to either acute prenatal androgen excess (PNA) or chronic peripubertal androgen excess (PPA). Females were phenotyped for reproductive and metabolic features associated with each model and brains of PNA mice were assessed for elevated GABAergic input to gonadotropin-releasing hormone (GnRH) neurons. Reproductive and metabolic dysfunction induced by PPA, including acyclicity, absence of corpora lutea, obesity, adipocyte hypertrophy, and impaired glucose homeostasis, was not different between GABARKO and wild-type (WT) mice. In PNA mice, acyclicity remained in GABARKO mice while ovarian morphology and luteinizing hormone secretion was not significantly impacted by PNA or genotype. However, PNA predictably increased the density of putative GABAergic synapses to GnRH neurons in adult WT mice, and this PNA-induced plasticity was absent in GABARKO mice. Together, these findings suggest that while direct androgen signaling in GABA neurons is largely not required for the development of PCOS-like traits in androgenized models of PCOS, developmental programming of GnRH neuron innervation is dependent upon androgen signaling in GABA neurons.

Key Considerations for Studying the Effects of High-Fat Diet on the Nulligravid Mouse Endometrium.

The obesity epidemic continues to increase, with half of US women predicted to be obese by 2030. Women with obesity are at increased risk for not only cardiovascular and liver disease, but also reproductive disorders. Although mouse models are useful in studying the effects of obesity, there is inconsistency in obesity-induction methods, diet composition, and mouse strains, and studies using female mice are limited. In this study, we sought to compare the effects of a 45% high-fat diet (HFD) versus a 60% HFD on the uterine estrous cycle of nulligravid C57BL/6J mice. For 22 weeks, we placed a total of 20 mice on either a 60% HFD, 45% HFD, or each HFD-matched control diet (CD). Both HFDs produced significant weight gain, with 60% HFD and 45% HFD gaining significant weight after 2 weeks and 15 weeks, respectively. Additionally, both HFDs led to glucose intolerance, fatty liver, and adipocyte hypertrophy. Mice fed 60% HFD displayed hyperphagia in the first 12 weeks of HFD treatment. Moreover, 60% HFD-treated mice had a longer estrous cycle length and an increased percentage of estrus stage samplings compared to CD-treated mice. Estrous cycle stage-controlled 60% HFD-treated mice displayed an increased estrogen-to-progesterone ratio and decreased ovarian corpora lutea compared to CD-treated mice, which may underlie the observed estrous cycle differences. There was no significant difference between diets regarding endometrial morphology or the percent of endometrial CD45+ immune cells. Our results indicate that consideration is needed when selecting a HFD-induced obesity mouse model for research involving female reproductive health.

Correlation of Body Mass Index and Lipid Profile in Young Adult

Objectives: Obesity, the primary risk factor for noncommunicable diseases, can be determined by calculating the body mass index. This condition is linked with extensive processes of adipocyte hyperplasia and hypertrophy caused by weight gain as a result of overnutrition and inadequate energy expenditure. These alterations in adipose tissue composition are linked to decreased adipokine production and the development of adipose tissue dysfunction, which is responsible for obesity-related metabolic disorders. Methods: This is a cross-sectional study involving 123 healthy volunteers with various BMIs. Data collection was carried out using interview techniques and then examined for BMI. The level of lipid serum was examined from venous blood. Results: From a total of 123 subjects, 97 people (78.8%) were male and 26 people (21.1%) were female. The mean age (SD) was 25.91±6.04 years. The quantity of data collected as well as the of abnormal BMI, TC, TG, HDL-C, and -C variables, which are 82 (66.7%), 46 (37.4%),36 (29.3%), 42 (34.1%), and 76 (61.8%), respectively. The correlation between BMI and TG (r=0.201,p=0.026), LDL-C (r=0.242, p=0.007), and LDL-C/HDL-C ratio (r=0.429, p=0.001). Correlation between BMI and HDLC (r=-0.430, p=0.001). Conclusion: There is a significant correlation between obesity and certain components of the lipid profile.International Journal of Human and Health Sciences Supplementary Issue 01: 2024 Page: S60

Comparative proteomic analysis of pathological characterization of adipose tissue remodeling induced by high-fat diet and high-carbohydrate diet in grass carp (Ctenopharyngodon idellus)

Our previous research found that excessive accumulation of adipose tissue is an important factor that reduces fish tolerance and utilization of high-energy feeds and limits the development of high-energy feeds in the aquaculture industry. However, the pathological characteristics and molecular mechanisms of fish adipose tissue remodeling caused by high-energy diet were still unclear. In this study, using histopathological observation, we found that restricted adipocyte hyperplasia, adipocyte hypertrophy, inflammation, and fibrosis are the main characteristics of pathological remodeling of fish adipose tissue induced by high-fat diet (HFD) and high-carbohydrate diet (HCD). Besides, this study further analyzed the molecular mechanisms and key marker proteins invovled in pathological remodeling of adipose tissue induced by HFD and HCD through comparative proteomics. The results found: (1) Inhibition of the differentiation of preadipocytes may be the main pathway through which both HCD and HFD inhibited adipocyte hyperplasia in grass carp; (2) Although both HFD and HCD induce adipocyte hypertrophy by increasing the de novo lipogenesis (DNL) pathway and promoting triglycerides (TG) synthesis. But the difference is that HFD increases fatty acid transport, while HCD increases glycolysis; (3) The inhibitory effect of HCD on glucose transporter type 4 (Glut4) may be an important cause of carbohydrate intolerance in fish; (4) Both HFD and HCD increase lactate production by promoting the expression of lactate dehydrogenase (Ldh), which may be the molecular mechanism of high-energy diet-induced adipose tissue hypoxia; (5) Interleukin-8 (Il-8) can be used as a pro-inflammatory marker for identifying HFD and HCD induced adipose tissue inflammation. This study aims to incestigate the reasons why HFD and HCD have negative effects on fish from the perspective of pathological remodeling of adipose tissue, and provide new underlying regulatory targets for improving the tolerance and utilization of HCD or HFD in farmed fish.

The Effect of Virgin Coconut Oil on TNFα and Cytochrome P450 Aromatase Levels in Obese Female White Rats (Rattus norvegicus) Induced with a High-Fat Diet

Background: The high level of various proinflammatory cytokines due to adipocyte hypertrophy such as TNFα in obesity increases cytochrome-P450-aromatase, further inducing increased estrogen production, hypersecretion of Luteinizing Hormone and decreased Follicle Stimulating Hormone, resulting in impaired folliculogenesis, and chronic anovulation. Virgin Coconut Oil is rich in Medium Chain Fatty Acid and phytochemicals as anti-inflammatory. Aim: The aim of this study was to determine the effect of VCO on reducing TNFα and cytochrome-P450-aromatase levels in obese female white rats. Methods: Post test only control group, 24 rats were divided into 3 groups, namely: negative control group (K-), positive control group (K+), and treatment group (P). The K+ and P groups were induced using a high-fat diet for 10 weeks, then the P group was given VCO in weeks 7-10. On the first day of week 11, blood was taken from the orbital vein of the eyes of all rats for TNFα levels. Both examinations used ELISA kits. Data analysis used Shapiro Wilks normality test. The value of p&gt;0.05, followed by hypothesis testing using one-way annova and post hoc Bonferroni. Results: Mean TNFα in the K- group: 141.71±8.87, K+ group: 15.09±19.30, P group: 162,09±13,57. Mean cytochrome-P450-aromatase levels in the K- group: 9.00±0.77, K+ group: 12.22±1.69, P group: 10.58±0.97. The mean levels of one way ANOVA analysis showed that the administration of VCO can significantly reduce TNFα levels (p=0.001) and significantly reduce Cytochrome-P450-aromatase levels (p=0.001). Conclusion: VCO administration can reduce TNFα levels and cytochorme-P450-aromatase levels in obese female white rats. Keywords: TNFα, cytochrome-P450-aromatase, infertility, obesity

Berberine attenuates obesity-induced insulin resistance by inhibiting miR-27a secretion.

Berberine (BBR) is an alkaloid found in plants. It has neuroprotective, anti-inflammatory and lipid-lowering activity. However, the efficacy of treatment with BBR and the mechanisms through which it acts need further study. This study investigated the therapeutic effects and the mechanism of action of BBR on obesity-induced insulin resistance in peripheral tissues. High-fat-fed C57BL/6J mice and low-fat-fed C57BL/6J mice with miR-27a overexpression were given BBR intervention (100 mg/kg, po), and the oral glucose tolerance test (OGTT) and insulin tolerance test (ITT) were performed. Palmitic acid-stimulated hypertrophic adipocyte models were treated with BBR (10 μM). Related indicators and protein expression levels were examined. The AUCs of the OGTT and the ITT in the BBR intervention group were reduced significantly (p < 0.01) (p < 0.05), and the serum biochemical parameters, including FBG, TC, TG and LDL-C were significantly reduced after BBR intervention. In the invitro experiments, the triglyceride level and volume of lipid droplets decreased significantly after BBR intervention (p < 0.01) (p < 0.05). Likewise, BBR ameliorates skeletal muscle and pancreas insulin signalling pathways invivo and invitro. The results showed that BBR significantly ameliorated insulin resistance, reduced body weight and percent body fat and improved serum biochemical parameters in mice. Likewise, BBR reduced triglyceride level and lipid droplet volume in hypertrophic adipocytes, BBR improved obesity effectively. Meanwhile, BBR ameliorated the histomorphology of the pancreas, and skeletal muscle and pancreas insulin related signalling pathways of islets in invitro and invivo experiments. The results further demonstrated that BBR inhibited miR-27a levels in serum from obese mice and supernatant of hypertrophic adipocytes. miR-27a overexpression in low-fat fed mice indicated that miR-27a caused insulin resistance, and BBR intervention significantly improved the miR-27a induced insulin resistance status. This study demonstrates the important role of BBR in obesity-induced peripheral insulin resistance and suggest that the mechanism of its effect may be inhibition of miR-27a secretion.

Western-style diet in the presence of elevated circulating testosterone induces adipocyte hypertrophy and t-cell dysfunction in rhesus macaques

Western-style diet in the presence of elevated circulating testosterone induces adipocyte hypertrophy and t-cell dysfunction in rhesus macaques

SLC25A28 Overexpression Promotes Adipogenesis by Reducing ATGL.

Adipose tissue dysfunction is seen among obese and type 2 diabetic individuals. Adipocyte proliferation and hypertrophy are the root causes of adipose tissue expansion. Solute carrier family 25 member 28 (SLC25A28) is an iron transporter in the inner mitochondrial membrane. This study is aimed at validating the involvement of SLC25A28 in adipose accumulation by tail vein injection of adenovirus (Ad)-SLC25A28 and Ad-green fluorescent protein viral particles into C57BL/6J mice. After 16 weeks, the body weight of the mice was measured. Subsequently, morphological analysis was performed to establish a high-fat diet (HFD)-induced model. SLC25A28 overexpression accelerated lipid accumulation in white and brown adipose tissue (BAT), enhanced body weight, reduced serum triglyceride (TG), and impaired serum glucose tolerance. The protein expression level of lipogenesis, lipolysis, and serum adipose secretion hormone was evaluated by western blotting. The results showed that adipose TG lipase (ATGL) protein expression was reduced significantly in white and BAT after overexpression SLC25A28 compared to the control group. Moreover, SLC25A28 overexpression inhibited the BAT formation by downregulating UCP-1 and the mitochondrial biosynthesis marker PGC-1α. Serum adiponectin protein expression was unregulated, which was consistent with the expression in inguinal white adipose tissue (iWAT). Remarkably, serum fibroblast growth factor (FGF21) protein expression was negatively related to the expansion of adipose tissue after administrated by Ad-SLC25A28. Data from the current study indicate that SLC25A28 overexpression promotes diet-induced obesity and accelerates lipid accumulation by regulating hormone secretion and inhibiting lipolysis in adipose tissue.

The Influence of Subcutaneous and Visceral Adipocyte Geometries on Metabolic Parameters and Metabolic Regulating Hormones in Obese and Non-Obese Subjects

Adipose tissue plays a pivotal role in endocrine and metabolic homeostasis. This study aimed to compare subcutaneous and visceral adipocyte measurements, including area, shortest diameter, longest diameter, and perimeter, between groups of different metabolic profiles; and to determine correlations of adipocyte geometries with metabolic parameters and hormones in obese (n=20) and non-obese subjects (n=14). We hypothesized that geometries of subcutaneous and visceral adipocytes differ between groups with distinct metabolic conditions, and that their measurements correlate with obesity parameters, metabolic profiles, and hormones differently within subcutaneous and visceral adipocyte parameters as well as between obese and non-obese subjects. A total of 34 subjects were classified based on insulin resistance, using the Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) &gt;2.3, and the presence of hypertension (HT), defined as systolic blood pressure (SBP)/diastolic blood pressure (DBP) ≥130/80 mmHg. These subjects underwent open abdominal surgery, with blood sample collection in a fasting state before the operation, and abdominal subcutaneous and omental (visceral) adipose tissue collection during the operation. Subjects with insulin resistance (n=6) and those with HT (n=15) both had a greater size of visceral adipocytes compared to those without insulin resistance (n=28) or HT (n=19), respectively; however, there were no significant differences in subcutaneous adipocyte size between the groups. For correlation analyses in obese subjects, subcutaneous adipocyte measurements exhibited significant positive correlations with visceral adipocyte measurements (R=0.592-0.630); while they showed significant negative correlations with cholesterol (R=-0.573) and serum visfatin (R=-0.610), all with p&lt;0.05. Furthermore, in obese subjects, visceral adipocytes geometries were positively correlated with body weight, waist circumference, and hip circumference (R=0.575-R=0.607), all with p&lt;0.05. In non-obese subjects, geometries of subcutaneous adipocytes were significantly positively correlated with body weight, BMI, waist circumference, and visceral adipocyte size (R=0.555-0.642); while were negatively correlated with serum adiponectin (R=(-0.608)-(-0.676)), all with p&lt;0.05. Furthermore, in non-obese subjects, the measurements of visceral adipocytes were significantly positively correlated with body weight, BMI, serum leptin levels, serum leptin/adiponectin ratio, waist circumference, and DBP (R=0.555-0.836); while were negatively correlated with serum adiponectin (R=(-0.608)-(-0.647), all with p&lt;0.05. These results suggest that hypertrophy of visceral adipocytes, rather than subcutaneous adipocytes, could contribute to insulin resistance and hypertension. Subcutaneous adipocyte size in obese subjects was not correlated with obesity parameters but was negatively correlated with cholesterol and visfatin levels potentially reflecting a protective effect or a compensatory mechanism in which an increase in subcutaneous fat might be a response to store excess lipids more safely when visceral fat capacity is limited. In non-obese subjects, visceral adipocyte geometries were positively correlated with DBP but inversely related to serum levels of adiponectin, an anti-inflammatory adipokine, indicating that larger adipocytes in non-obese individuals are not benign but indicative of early metabolic derangement. In conclusion, subcutaneous fat in obese individuals may represent a potentially protective effect or compensatory response to metabolic disturbance induced by excess visceral fat. In non-obese individuals, a larger visceral adipocyte size could signal early metabolic alterations, even in the absence of obesity. The research was funded by the Faculty of Medicine Siriraj Hospital Research Fund ((IO) R015332009). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.