Visceral Adipose Tissue Weight Research Articles

Estrogen restores disordered lipid metabolism in visceral fat of prediabetic mice.

Visceral obesity is increasingly prevalent among adolescents and young adults and is commonly recognized as a risk factor for type 2 diabetes. Estrogen [17β-estradiol (E2)] is known to offer protection against obesity via diverse me-chanisms, while its specific effects on visceral adipose tissue (VAT) remain to be fully elucidated. To investigate the impact of E2 on the gene expression profile within VAT of a mouse model of prediabetes. Metabolic parameters were collected, encompassing body weight, weights of visceral and subcutaneous adipose tissues (VAT and SAT), random blood glucose levels, glucose tolerance, insulin tolerance, and overall body composition. The gene expression profiles of VAT were quantified utilizing the Whole Mouse Genome Oligo Microarray and subsequently analyzed through Agilent Feature Extraction software. Functional and pathway analyses were conducted employing Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses, respectively. Feeding a high-fat diet (HFD) moderately increased the weights of both VAT and SAT, but this increase was mitigated by the protective effect of endogenous E2. Conversely, ovariectomy (OVX) led to a significant increase in VAT weight and the VAT/SAT weight ratio, and this increase was also reversed with E2 treatment. Notably, OVX diminished the expression of genes involved in lipid metabolism compared to HFD feeding alone, signaling a widespread reduction in lipid metabolic activity, which was completely counteracted by E2 administration. This study provides a comprehensive insight into E2's local and direct protective effects against visceral adiposity in VAT at the gene level. In conclusion, the present study demonstrated that the HFD-induced over-nutritional challenge disrupted the gene expression profile of visceral fat, leading to a universally decreased lipid metabolic status in E2 deficient mice. E2 treatment effectively reversed this condition, shedding light on the mechanistic role and therapeutic potential of E2 in combating visceral obesity.

The Association between Visceral Adipose Tissue and Coronary Atherosclerosis in Thai Postmortem Cases

Objective: To determine the correlation between visceral adipose tissue (VAT) and degree of coronary artery stenosis in the Thai population. Materials and Methods: This prospective cross-sectional study was conducted in 220 Thai postmortem cases. Sex, age, weight, height, waist and hip circumferences were recorded for each case. The intra-abdominal VAT weight of each site was assessed during the autopsy procedure, and degrees of stenosis for three coronary arteries (left anterior descending artery (LAD), right coronary artery (RCA) and left circumflex artery (LCX)) were evaluated in histological examination. Descriptive statistics, bivariate correlation, and multivariate linear regression were used to determine the correlations between VAT and degrees of coronary artery stenosis. Results: There were 108 female and 112 male subjects with a mean age of 45.95 years old. Waist circumference, waist-hip ratio and VAT in the male subjects were significantly higher than in the female subjects (p<0.001). VAT was well correlated with waist circumference and waist-hip ratio (p<0.001). VAT weights were positively correlated with degrees of LAD, RCA and LCX stenosis, with coefficient correlations (r) of 0.561, 0.453 and 0.451, respectively (p<0.001). Mesenteric and peri-renal adipose tissues produced better correlations than the other sites. Multivariate linear regression showed that sex and age were correlated with stenosis in all three coronary arteries (p<0.001), and mesenteric and peri-renal adipose tissues had strong correlations with LAD stenosis (p<0.001). Conclusion: VAT weights from all sites were correlated with degrees of coronary artery stenosis. Mesenteric and peri-renal adipose tissues produced better correlations than the other sites.

Rebaudioside D decreases adiposity and hepatic lipid accumulation in a mouse model of obesity

Overconsumption of added sugars has been pointed out as a major culprit in the increasing rates of obesity worldwide, contributing to the rising popularity of non-caloric sweeteners. In order to satisfy the growing demand, industrial efforts have been made to purify the sweet-tasting molecules found in the natural sweetener stevia, which are characterized by a sweet taste free of unpleasant aftertaste. Although the use of artificial sweeteners has raised many concerns regarding metabolic health, the impact of purified stevia components on the latter remains poorly studied. The objective of this project was to evaluate the impact of two purified sweet-tasting components of stevia, rebaudioside A and D (RebA and RebD), on the development of obesity, insulin resistance, hepatic health, bile acid profile, and gut microbiota in a mouse model of diet-induced obesity. Male C57BL/6 J mice were fed an obesogenic high-fat/high-sucrose (HFHS) diet and orally treated with 50 mg/kg of RebA, RebD or vehicle (water) for 12 weeks. An additional group of chow-fed mice treated with the vehicle was included as a healthy reference. At weeks 10 and 12, insulin and oral glucose tolerance tests were performed. Liver lipids content was analyzed. Whole-genome shotgun sequencing was performed to profile the gut microbiota. Bile acids were measured in the feces, plasma, and liver. Liver lipid content and gene expression were analyzed. As compared to the HFHS-vehicle treatment group, mice administered RebD showed a reduced weight gain, as evidenced by decreased visceral adipose tissue weight. Liver triglycerides and cholesterol from RebD-treated mice were lower and lipid peroxidation was decreased. Interestingly, administration of RebD was associated with a significant enrichment of Faecalibaculum rodentium in the gut microbiota and an increased secondary bile acid metabolism. Moreover, RebD decreased the level of lipopolysaccharide-binding protein (LBP). Neither RebA nor RebD treatments were found to impact glucose homeostasis. The daily consumption of two stevia components has no detrimental effects on metabolic health. In contrast, RebD treatment was found to reduce adiposity, alleviate hepatic steatosis and lipid peroxidation, and decrease LBP, a marker of metabolic endotoxemia in a mouse model of diet-induced obesity.

Daily Consumption of Golden Berry (Physalis peruviana) Has Been Shown to Halt the Progression of Insulin Resistance and Obesity in Obese Rats with Metabolic Syndrome.

In a study addressing the high risk of chronic diseases in people with diabetes and obesity linked to metabolic syndrome, the impact of a Golden Berry diet was investigated using a diabetic animal model. Obese rats with diabetic characteristics were fed a diet containing five percent Golden Berry for 16 days. This study focused on various parameters including organ weights, expression of metabolic genes, and urinary biomarkers. Post-Golden Berry intake, there was a notable decrease in the body, liver, pancreas, visceral, and subcutaneous adipose tissue weights in these obese, hyperglycemic rats. In contrast, an increase in brown adipose tissue (BAT) cell mass was observed. This diet also resulted in reduced blood glucose levels and normalized plasma biochemical profiles, including cholesterol, triglycerides, LDL, and HDL levels. Additionally, it modulated specific urinary biomarkers, particularly pipe-colic acid, a primary marker for type 2 diabetes. Bioinformatics analysis linked these dietary effects to improved insulin signaling and adipogenesis. Regular consumption of Golden Berry effectively prevented insulin resistance and obesity in rats, underscoring its significant health benefits and the protective role of an antioxidant-rich diet against metabolic syndrome. These findings offer promising insights for future therapeutic strategies to manage and prevent obesity and related chronic diseases.

Metabolic remodeling of visceral and subcutaneous white adipose tissue during reacclimation of rats after cold.

Deciphering lipid metabolism in white adipose tissue (WAT) depots during weight gain is important to understand the heterogeneity of WAT and its roles in obesity. Here, we examined the expression of key enzymes of lipid metabolism and changes in the morphology of representative visceral (epididymal) and subcutaneous (inguinal) WAT (eWAT and iWAT, respectively)-in adult male rats acclimated to cold (4 ± 1°C) for 45 days and reacclimated to room temperature (RT, 22 ± 1°C) for 1, 3, 7, 12, 21, or 45 days. The relative mass of both depots decreased to a similar extent after cold acclimation. However, fatty acid synthase (FAS), glucose-6-phosphate dehydrogenase (G6PDH), and medium-chain acyl-CoA dehydrogenase (ACADM) protein level increased only in eWAT, whereas adipose triglyceride lipase (ATGL) expression increased only in iWAT. During reacclimation, the relative mass of eWAT reached control values on day 12 and that of iWAT on day 45 of reacclimation. The faster recovery of eWAT mass is associated with higher expression of FAS, acetyl-CoA carboxylase (ACC), G6PDH, and ACADM during reacclimation and a delayed increase in ATGL. The absence of an increase in proliferating cell nuclear antigen suggests that the observed depot-specific mass increase is predominantly due to metabolic adjustments. In summary, this study shows a differential rate of visceral and subcutaneous adipose tissue weight regain during post-cold reacclimation of rats at RT. Faster recovery of the visceral WAT as compared to subcutaneous WAT during reacclimation at RT could be attributed to observed differences in the expression patterns of lipid metabolic enzymes.

LIGHT/TNFSF14 Affects Adipose Tissue Phenotype.

LIGHT/TNFSF14 is linked to several signaling pathways as a crucial member of a larger immunoregulatory network. It is primarily expressed in inflammatory effector cells, and high levels of LIGHT have been reported in obesity. Thus, with the aim of deepening the knowledge of the role of LIGHT on adipose tissue phenotype, we studied wild-type (WT), Tnfsf14-/-, Rag-/- and Rag-/Tnfsf14- (DKO) mice fed a normal diet (ND) or high-fat diet (HFD). Our results show that, although there is no significant weight gain between the mice with different genotypes, it is significant within each of them. We also detected an increase in visceral White Adipose Tissue (vWAT) weight in all mice fed HFD, together with the lowest levels of vWAT weight in Tnfsf14-/- and DKO mice fed ND with respect to the other strain. Inguinal WAT (iWAT) weight is significantly affected by genotype and HFD. The least amount of iWAT was detected in DKO mice fed ND. Histological analysis of vWAT showed that both the genotype and the diet significantly affect the adipocyte area, whereas the number is affected only by the genotype. In iWAT, the genotype and the diet significantly affect mean adipocyte area and number; interestingly, the area with the least adipocyte was detected in DKO mice fed ND, suggesting a potential browning effect due to the simultaneous lack of mature lymphocytes and LIGHT. Consistently, Uncoupling Protein 1 (UCP1) staining of iWAT demonstrated that few positive brown adipocytes appeared in DKO mice. Furthermore, LIGHT deficiency is associated with greater levels of UCP1, highlighting the lack of its expression in Rag-/- mice. Liver examination showed that all mice fed HFD had a steatotic liver, but it was particularly evident for DKO mice. In conclusion, our study demonstrates that the adipose tissue phenotype is affected by LIGHT levels but also much more by mature lymphocytes.

A fat- and sucrose-enriched diet causes metabolic alterations in mdx mice.

Duchenne muscular dystrophy (DMD), a progressive muscle disease caused by the absence of functional dystrophin protein, is associated with multiple cellular, physiological, and metabolic dysfunctions. As an added complication to the primary insult, obesity/insulin resistance (O/IR) is frequently reported in DMD patients; however, how IR impacts disease severity is unknown. We hypothesized a high-fat, high sucrose diet (HFHSD) would induce O/IR, exacerbate disease severity, and cause metabolic alterations in dystrophic mice. To test this hypothesis, we treated 7-wk old mdx (disease model) and C57 mice with a control diet (CD) or a HFHSD for 15 weeks. The HFHSD induced insulin resistance, glucose intolerance and hyperglycemia in C57 and mdx mice. Of note, mdx mice on CD were also insulin resistant. Additionally, visceral adipose tissue weights were increased with HFHSD in C57 and mdx mice though differed by genotype. Serum creatine kinase activity and histopathological analyses using Masson's trichrome staining in diaphragm indicated muscle damage was driven by dystrophin deficiency but was not augmented by diet. In addition, markers of inflammatory signaling, mitochondrial abundance, and autophagy were impacted by disease but not diet. Despite this, in addition to disease signatures in CD-fed mice, metabolomic and lipidomic analyses demonstrated a HFHSD caused some common changes in C57 and mdx mice and some unique signatures of O/IR within the context of dystrophin deficiency. In total, these data revealed that in mdx mice, 15 weeks of a HFHSD did not overtly exacerbate muscle injury but further impaired the metabolic status of dystrophic muscle.

Dietary Bamboo Charcoal Decreased Visceral Adipose Tissue Weight by Enhancing Fecal Lipid Excretions in Mice with High-Fat Diet-Induced Obesity.

Bamboo charcoal (BC) powder is prepared from thick bamboo stems via dry distillation and is often used for food coloring. Due to the unique structure of the micropores in bamboo stems, BC powder also serves as an indigestible carrier to prevent the absorption of toxic substances and nutrients from the digestive tract. This study evaluated the health-promoting function of BC, particularly its effects in decreasing visceral adipose tissue in a mouse model with high-fat diet (HFD)-induced obesity. Four-week-old male C57BL/6J mice were divided into three groups and fed either a low-fat (LF) diet (7% fat), HF diet (25% fat), or HF diet with 0.5% BC (HF-BC). After 80 days, the HF-BC diet was found to have decreased epididymal and mesenteric white adipose tissue weights compared to HFD. The inhibition of visceral fat accumulation by BC intake was partly due to enhanced fecal fatty acid excretion induced by its bile acid-binding and pancreatic lipase inhibition. Contrarily, the gut microbiota, known to influence systemic energy metabolism, did not change significantly between the HF and HF-BC groups. These results indicate that dietary BC inhibits visceral fat accumulation, which could reduce obesity development.

Cafeteria diet-induced obesity remodels immune response in acute Trypanosoma cruzi infection

BackgroundObesity is a global problem associated with several conditions, including hypertension, diabetes, arthritis and cardiovascular diseases. With the increase in the prevalence of obesity in recent years, mostly in developing countries, it is important to study its impact on various diseases, including infectious illnesses, such as Chagas disease, caused by the protozoan Trypanosoma cruzi. Considering that a diet rich in salt, sugar, and fat is associated with obesity, this study aimed to evaluate the influence of cafeteria diet (CAF)-induced obesity on immune responses in T. cruzi-infected rats. MethodsMale Wistar Hannover rats were provided with water and food ad libitum (chow group). The CAF-fed groups received a normal rodent diet or CAF. The animals were intraperitoneally infected with 105 trypomastigote forms of the Y strain of T. cruzi present in the whole blood from a previously infected mouse. ResultsCAF-fed rats showed a significant increase in visceral adipose tissue weight compared to chow-fed rats. A significant reduction in CD3+ CD4+ helper splenic T cells was observed in obese-infected rats compared to non-obese-infected rats, as well as CD11b and macrophages. In addition, macrophages from obese animals displayed reduced RT1b levels compared to those from control animals. Moreover, INF-γ, an important factor in macrophage activation, was reduced in obese-infected rats compared with their counterparts. ConclusionsThese results indicate that a CAF can impair the cell-mediated immune response against T. cruzi.

Abstract P303: Contribution Of Adrenal Leptin Receptor To The Control Of Aldosterone Synthase Expression And Endothelial Function In Female Mice

While premenopausal women are severally affected by the current obesity epidemic, the mechanisms whereby obesity promotes vascular dysfunction in this population remain ill-defined. We previously demonstrated that the adipokine leptin acts on the adrenal gland to promote aldosterone production and that leptin-mediated aldosterone production impairs endothelial function in female mice only. Herein, we investigated whether these mechanisms are dependent on the presence of leptin receptors (lepR) in adrenal glands. We generated lean female mice exhibiting a selective deficiency in LepR in adrenals (AdKO), and obese mice expressing LepR in adrenal glands (db/ad + ) only. Under baseline conditions, AdKO exhibited no alteration in adrenal CYP11B2, renal renin level, aortic endothelial function (measured by acetylcholine-mediated relaxation), arterial stiffness (pulse wave velocity test, PWV), or metabolic parameters including heart and visceral adipose tissue (VAT) weights, fluid amount, glycemia, and HbA1c. Chronic leptin infusion for a week induced trends towards increases in adrenal CYP11B2 (ΔΔCt 1.10±0.12 vs 2.01±0.51, P=0.077), aldosterone (557±95 vs 918±526 pg/ml, P=0.859), and renin levels in WT. AdKO conferred no protection against any of these changes. Leptin infusion impaired endothelial function in WT (Emax 73.3±3.9 vs 52.8±3.1%, P=0.019), which was exacerbated in AdKO (52.8±3.1 vs 34.3±4.1%, P=0.052). However, leptin infusion did not change PWV in WT (3.93±0.22 vs 4.17±0.32 m/s, P=0.999), but induced a trend towards a decrease in AdKO (4.17±0.32 vs 3.11±0.44 m/s, P=0.228). Restoration of adrenal LepR in db/db mice did not alter CYP11B2 nor aldosterone levels but increased renin (ΔΔCt 1.04±0.11 vs 1.48±0.12, P=0.029), heart weight, VAT weight (5.14±0.29 vs 6.52±0.62 g/g, P=0.052), and HbA1c (5.7±0.2 vs 6.9±0.4 %, P=0.035). Although PWV was worsened in db/ad + (5.40±0.27 vs 6.39±0.49 m/s, P=0.035), db/ad + presented improved relaxation compared to db/db (58.5±5.6 vs 73.0±2.2%, P=0.067), inconsistent with our hypothesis. Collectively these data indicate that adrenal LepR might not directly control adrenal CYP11B2 levels expression but latently contributes to changes in endothelial function and arterial stiffness.

Abstract P340: Codonopsis Lanceolata Extract Prevents Metabolic And Cardiovascular Alterations In Short-term High-fat/high-fructose Diet-fed Adolescent Rats

Fast food consumption, which has increased among adolescents, has been associated with the risk of cardio-metabolic disorders. However, the effects of short-term high-fat/high-fructose diet (HFFD) on cardiovascular and metabolic parameters in adolescent rats has not yet been evaluated. Also, preventive effects of codonopsis lanceolata (CL) in these rats are unknown. Therefore, we investigated the effects of short-term HFFD consumption on cardiovascular and metabolic factors in adolescent rats, as well as the preventive effects of CL extract. Adolescent rats were fed a 60% high-fat diet plus 10% fructose water for 2 weeks. During this time, CL extract (200 or 400 mg/kg) was administered once daily. Short-term HFFD increased visceral white adipose tissue (WAT) weight, fasting blood sugar (FBS) concentration and water intake in adolescent rats. This diet also significantly increased systolic blood pressure (SBP), heart rate, and phenylephrine-induced vasocontraction. CL extract, however, effectively reduced visceral WAT weight, FBS, SBP and heart rate in short-term HFFD-fed adolescent rats. These findings indicate that exposure to HFFD for only 2 weeks induced cardiovascular and metabolic alterations in adolescent rats and that CL extract is effective in preventing these harmful effects of short-term HFFD in adolescent rats. This work was by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (No. 2021R1A2C2004118). * Corresponding author. Keywords: high-fat/high-fructose diet; adolescent; codonopsis lanceolata ; prevention; visceral white adipose tissue; fasting blood sugar; systolic blood pressure

Efficacy of Carotenoid-Loaded Gelatin Nanoparticles in Reducing Plasma Cytokines and Adipocyte Hypertrophy in Wistar Rats

The present study investigated the effect of gelatin-based nanoparticles (EPG) loaded with a carotenoid-rich crude extract (CE) on systemic and adipose tissue inflammatory response in a model with inflammation induced by a high glycemic index and high glycemic load diet (HGLI). Nanoparticles synthesized were characterized by different physical and chemical methods. The in vivo investigation evaluated Wistar rats (n = 20, 11 days, adult male with 21 weeks) subdivided into untreated (HGLI diet), conventional treatment (nutritionally adequate diet), treatment 1 (HGLI + crude extract (12.5 mg/kg)), and treatment 2 (HGLI + EPG (50 mg/kg)) groups. Dietary intake, caloric intake and efficiency, weight, inflammatory cytokines tissue concentration, visceral adipose tissue (VAT) weight, histopathological analysis, and antioxidant activity in plasma and VAT were investigated. EPG showed the same physical and chemical characteristics as previous batches (95.2 nm, smooth surface, and chemical interactions between materials). The EPG-treated group was the only group promoting negative ∆dietary intake, ∆caloric efficiency, and ∆weight. In addition, it presented a significant reduction (p < 0.05) in IL-6 and leptin levels and a greater presence of multilocular adipocytes. The results suggest that EPG can act as a nutraceutical in adjuvant therapy for treating inflammatory diseases associated with adipose tissue accumulation.

311-OR: Role of Pcpe2 in Adipose Tissue Remodeling and Expansion

Prevalence of obesity in the US continues to drive greater risk for type 2 diabetes and cardiovascular disease. Excessive caloric intake stresses adipocytes into storing lipid in an unhealthy manner, directing lipid into existing adipocytes, or hypertrophy. Healthy adipose expansion occurs when adipose tissue precursor cells (PC) in the stromal vascular fraction (SVF) differentiate to create new pre-adipocytes which store lipid, called hyperplasia. Single cell sequencing of visceral adipose tissue (VAT) have identified two main types of PCs in the SVF, one called adipocyte precursor cells (APCs), while the other is a fibro-inflammatory progenitors (FIPs). APC are pre-adipocytes which differentiate into mature adipocytes, while FIPs, secrete cytokines inhibiting APC differentiation. Influencing APC and FIP lineage are the transforming growth factor beta (TGFb)-like signaling which inhibit adipogenesis, while bone morphogenetic protein (BMP)-like signaling promotes adipogenesis. Little is known about how signaling alters APCs and FIPs fate, especially during increased lipoprotein flux from high fat diet (HFD). Recently we discovered that both VAT PCs, APCs and FIPs express high levels of the extracellular matrix (ECM) protein, procollagen endopeptidase enhancer protein 2 (Pcpe2) whose expression decreases as APCs become committed adipocytes. We found that Pcpe2 is upregulated ~4-fold by both TGFb1, and HFD feeding suggesting that Pcpe2 plays a role in TGFb-like pathways in VAT PCs. Using PC-specific Pcpe2-hemagglutinin tagged (HA) over-expressor (ox) (PC-PcpeoxHA) and PC cell-specific Pcpe2 knockout (KO) (PC-Pcpe2KO) mice lines, show PC-Pcpe2KO mice have reduced (~35-40%) body and VAT weight, while PC-PcpeoxHA mice showed an increase (~40-45%) in body and VAT weight. In other studies we show APC rates of proliferation and differentiation are highly dependent on Pcpe2 expression. Overall, these studies reveal novel mechanistic insight into the mechanisms involved in dysfunctional fat storage. Disclosure M.G.Sorci-thomas: None. H.Xu: None. M.J.Thomas: None.

Abstract 448: Role Of Pcpe2 In Adipose Tissue Remodeling And Lipoprotein Metabolism

Increased prevalence of obesity in the US continues to drive greater risk for developing type 2 diabetes and cardiovascular disease. Excessive caloric intake stresses adipocytes into storing lipid in an unhealthy manner, directing lipid into existing adipocytes, or adipocyte hypertrophy. Healthy adipose tissue expansion and remodeling occurs when adipose tissue precursor cells (PC) in the stromal vascular fraction (SVF) differentiate to create new pre-adipocytes which store lipid, called hyperplasia. Single cell sequencing of visceral adipose tissue (VAT) have identified two main types of PCs in the SVF, one called adipocyte precursor cells (APCs), while the other is a fibro-inflammatory progenitors (FIPs). APC are pre-adipocytes which given the proper signals, differentiate into mature adipocytes, while FIPs, can secrete cytokines inhibiting APC differentiation and initiating inflammation. Also influencing APC and FIP lineage in the SVF are the transforming growth factor beta (TGFb)-like signaling pathways which inhibit adipogenesis, while bone morphogenetic protein (BMP)-like signaling promotes adipogenesis. Little is known about how signaling through these pathways alters APCs and FIPs fate, especially during increased lipoprotein flux from high fat diet (HFD). Recently we discovered that both VAT PCs, APCs and FIPs express high levels of the extracellular matrix (ECM) protein, procollagen endopeptidase enhancer protein 2 (Pcpe2 ) whose expression decreases as APCs become committed adipocytes. We found that Pcpe2 is significantly up-regulated ~4-fold by TGFb1 suggesting that Pcpe2 plays a role in TGFb-like pathways in VAT PCs. Using PC-specific Pcpe2-hemagglutinin tagged (HA) overexpressor (ox) (PC-Pcpe oxHA ) and PC cell-specific Pcpe2 knockout (KO) (PC-Pcpe2 KO ) mice lines, studies show PC-Pcpe2 KO mice have reduced (~35-40%) body and VAT weight, while PC-Pcpe oxHA mice showed an increase (~40-45%) in body and VAT weight, characterized by hypertrophic adipocytes. In other studies we show APC rates of proliferation and differentiation are highly dependent on Pcpe2 expression. Overall, these studies reveal novel mechanistic insight into the mechanisms involved in dysfunctional fat storage.

Estrogen contributes to the sex difference in the occurrence of senescence-related T cells during the development of visceral adipose tissue inflammation.

It remains unclear whether sex differences exist during the development of visceral adipose tissue (VAT) inflammation associated with obesity. The purpose of this study was to clarify sex differences in the occurrence of senescence-related T cells (CD44high PD-1+ CD4+), which play a key role in the progression of VAT inflammation associated with high-fat diet (HFD)-induced obesity. Phase 1: C57BL/6N mice were fed either a control diet (HFC) or HFD for 5 wk. The area under the curve of the oral glucose-tolerance test (oGTT) was maximal at 15 wk in HFD-fed males and at 21 wk in females. At 17 wk, VAT weights were similar, but an increase in the number of macrophages in the VAT was observed only in HFD-fed males. In addition, the numbers of regulatory and senescence-related T cells were consistently higher in males than in females. Phases 2 and 3: 6-wk-old female mice were randomly divided into sham operation and bilateral ovariectomy (OVX) groups and fed either an HFC or HFD from 7 wk. OVX mice were subjected to 17β-estradiol releasing or placebo pellet implantation and fed an HFC. Body and VAT weights were higher in the OVX group than in the sham. The number of macrophages did not change in the OVX group with either diet. HFC-fed OVX mice exhibited high senescence-related T cells in the VAT, resembling HFC-fed male mice. This change was abolished by 17β-estradiol replacement. Thus, we demonstrated different accumulation patterns of VAT immune cells between the sexes, revealing a role for estrogen in the appearance of senescence-related T cells.NEW & NOTEWORTHY The accumulation pattern of adipose tissue differs between the sexes; however, it is unclear whether sex differences exist during the development of adipose tissue inflammation and whether estrogen plays a role. We demonstrated sex differences in immune cells' subpopulation of visceral adipose tissue. The proinflammatory environment appeared earlier in males than in females. In addition, our results suggest that estrogen plays a role in visceral adipose tissue inflammation, particularly by regulating the appearance of senescence-related T cells.

Acacetin alleviates energy metabolism disorder through promoting white fat browning mediated by AC-cAMP pathway.

Acacetin (ACA), a flavone isolated from Chinese traditional medical herbs, has numerous pharmacological activities. However, little is known about the roles in white fat browning and energy metabolism. In the present study, we investigated whether and how ACA would improve energy metabolism in vivo and in vitro. ACA (20 mg/kg) was intraperitoneally injected to the mice with obesity induced by HFD for 14 consecutive days (in vivo); differentiated 3T3-L1 adipocytes were treated with ACA (20 µmol/L and 40 µmol/L) for 24 h (in vitro). The metabolic profile, lipid accumulation, fat-browning and mitochondrial contents, and so on were respectively detected. The results in vivo showed that ACA significantly reduced the body weight and visceral adipose tissue weight, alleviated the energy metabolism disorder, and enhanced the browning-related protein expressions in adipose tissue of rats. Besides, the data in vitro revealed that ACA significantly reduced the lipid accumulation, induced the expressions of the browning-related proteins and cAMP-dependent protein kinase A (PKA), and increased the mitochondrium contents, especially enhanced the energy metabolism of adipocytes; however, treatment with beta-adrenergic receptor blocker (propranolol, Pro) or adenyl cyclase (AC) inhibitor (SQ22536, SQ) abrogated the ACA-mediated effects. The data demonstrate that ACA alleviates the energy metabolism disorder through the pro-browning effects mediated by the AC-cAMP pathway. The findings would provide the experimental foundation for ACA to prevent and treat obesity and related metabolism disorders.

Gender features of metabolic syndrome components in young age

The article analyzes the clinical and laboratory features of young men and women with abdominal obesity and metabolic syndrome. The study was carried out on 173 patients of both sexes aged 18-45 years. The patients were divided into 3 groups: group 1 – isolated abdominal obesity (AO); group 2 – combination of abdominal obesity with 1 of the metabolic syndrome components (AO+1); group 3 – metabolic syndrome (MetS). It was found that in young men, the values of carbohydrate (glucose, insulin) and lipid metabolism (HDL cholesterol, LDL cholesterol, triglycerides), insulin resistance indices (HOMA-IR, TyG) in the AO and AO+1 groups were homogeneous. However, the ratio of TG/HDL in the AO+1 group exceeded the value of the AO group. Women in the AO+1 group showed changes relative to the group of women with isolated AO that are hyperglycemia, increased LDL cholesterol, insulin resistance (increased TG/HDL) and dysfunction of visceral adipose tissue (increased VAI). Young men with MetS are characterized by excess body weight, hyperglycemia, dyslipidemia (increased LDL cholesterol and triglycerides), insulin resistance (as measured by TyG and TG/HDL), and dysfunction of visceral adipose tissue. The gender feature of women is the development of MetS on the background of obesity, dysfunction of visceral adipose tissue and insulin resistance in combination with deeper changes in lipid metabolism (increased LDL cholesterol and triglycerides, as well as a decrease in HDL cholesterol).

Early-life dietary exposures mediate persistent shifts in the gut microbiome and visceral fat metabolism.

In utero dietary exposures are linked to the development of metabolic syndrome in adult offspring. These dietary exposures can potentially impact gut microbial composition and offspring metabolic health. Female BALB/c mice were administered a lard, lard + flaxseed oil, high sugar, or control diet 4 wk before mating, throughout mating, pregnancy, and lactation. Female offspring were offered low-fat control diet at weaning. Fecal 16S sequencing was performed. Untargeted metabolomics was performed on visceral adipose tissue (VAT) of adult female offspring. Immunohistochemistry was used to determine adipocyte size, VAT collagen deposition, and macrophage content. Hippurate was administered via weekly intraperitoneal injections to low-fat and high-fat diet-fed female mice and VAT fibrosis and collagen 1A (COL1A) were assessed by immunohistochemistry. Lard diet exposure was associated with elevated body and VAT weight and dysregulated glucose metabolism. Lard + flaxseed oil attenuated these effects. Lard diet exposures were associated with increased adipocyte diameter and VAT macrophage count. Lard + flaxseed oil reduced adipocyte diameter and fibrosis compared with the lard diet. Hippurate-associated bacteria were influenced by lard versus lard + flax exposures that persisted to adulthood. VAT hippurate was increased in lard + flaxseed oil compared with lard diet. Hippurate supplementation mitigated VAT fibrosis pathology. Maternal high-fat lard diet consumption resulted in long-term metabolic and gut microbiome programming in offspring, impacting VAT inflammation and fibrosis, and was associated with reduced VAT hippurate content. These traits were not observed in maternal high-fat lard + flaxseed oil diet-exposed offspring. Hippurate supplementation reduced VAT fibrosis. These data suggest that detrimental effects of early-life high-fat lard diet exposure can be attenuated by dietary omega-3 polyunsaturated fatty acid supplementation.

Antihypertensive Effect of Dietary β-Conglycinin in the Spontaneously Hypertensive Rat (SHR).

Dietary β-conglycinin has been shown to increase plasma adiponectin concentration and decrease visceral adipose tissue weight in rats. Since adiponectin is one of the factors regulating blood pressure, as well as modulating lipid metabolism, we examined whether dietary β-conglycinin affects blood pressure in spontaneously hypertensive rats. The experimental diets were prepared according to the AIN-93G formula containing 20% protein, either casein (Control) or casein replaced with soy protein isolate (SOY) or β-conglycinin (β-CON) at the proportion of 50%. Male rats (SHR/Izm, 6 wk-old) were fed the diets for 7 weeks. The SOY compared with the Control significantly suppressed the blood pressure both at week 4 (p = 0.011, Control vs. SOY) and thereafter, and β-CON had even higher suppression (p = 0.0002, Control vs. β-CON). SOY and β-CON increased plasma adiponectin concentration followed by an increase in plasma nitric oxide and possibly a decreasing trend of gene expressions of angiotensinogen in the liver and renin in the kidney. The results indicated suppression by β-conglycinin of increasing blood pressure through an enhancement of plasma adiponectin, probably in combination with a regulation of the renin–angiotensin system in spontaneously hypertensive rats.

Comprehensive lipidomic analysis reveals regulation of glyceride metabolism in rat visceral adipose tissue by high-altitude chronic hypoxia.

Adipose tissue plays a central role in energy substrate homeostasis and is a key regulator of lipid flow throughout these processes. As hypoxia affects lipid metabolism in adipose tissue, we aimed to investigate the effects of high-altitude chronic hypoxia on lipid metabolism in the adipose tissue of rats using a lipidomic analysis approach. Visceral adipose tissues from rats housed in a high-altitude hypoxia environment representing 4,300 m with 14.07% oxygen (hypoxia group) and from rats housed in a low-altitude normoxia environment representing 41 m with 20.95% oxygen (normoxia group) for 8 weeks were analyzed using an ultra-performance liquid chromatography-Orbitrap mass spectrometry system. After 8 weeks, the body weight and visceral adipose tissue weight of the hypoxia group were significantly decreased compared to those of the normoxia group (p < 0.05). The area and diameter of visceral adipose cells in the hypoxia group were significantly smaller than those of visceral adipose cells in the normoxia group (p < 0.05). The results of lipidomic analysis showed a total of 21 lipid classes and 819 lipid species. The total lipid concentration of the hypoxia group was lower than that in the normoxia group (p < 0.05). Concentrations of diacylglycerols and triacylglycerols in the hypoxia group were significantly lower than those in the normoxia group (p < 0.05). Using univariate and multivariate analyses, we identified 74 lipids that were significantly altered between the normoxia and hypoxia groups. These results demonstrate that high-altitude chronic hypoxia changes the metabolism of visceral adipose glycerides, which may potentially modulate other metabolic processes.