Visceral Adipose Tissue Accumulation Research Articles

Fish oil supplementation in obese rats ameliorates metabolic syndrome response.

Accumulation of visceral adipose tissue is associated with metabolic syndrome (MS), insulin resistance, and dyslipidemia. Here we examined several morphometric and biochemical parameters linked to MS in a rodent litter size reduction model, and how a 30-day fish oil (FO) supplementation affected these parameters. On day 3 post-birth, pups were divided into groups of ten or three. On day 22, rats were split into control (C) and small litter (SL) until 60 days old. Then, after metabolic disturbance and obesity were confirmed, FO supplementation started for 30 days and the new groups were named control (C), FO supplemented (FO), obese (Ob), and obese FO supplemented (ObFO). Comparison was performed by Student t-test or 2-way ANOVA followed by Tukey post hoc test. At the end of the 60-day period, SL rats were hyperphagic, obese, hypoinsulinemic, normoglycemic, and had high visceral fat depot and high interleukin (IL)-6 plasma concentration. Obese rats at 90 days of age were fatter, hyperphagic, hyperglycemic, hypertriacylgliceromic, hipoinsulinemic, with low innate immune response. IL-6 production ex vivo was higher, but in plasma it was not different from the control group. FO supplementation brought all biochemical changes to normal values, normalized food intake, and reduced body weight and fat mass in obese rats. The innate immune response was improved but still not as efficient as in lean animals. Our results suggested that as soon MS appears, FO supplementation must be used to ameliorate the morpho- and biochemical effects caused by MS and improve the innate immune response.

Endothelium-Independent Anti-Contractile Effect of Rat Aorta Perivascular Adipose Tissue at Control and Metabolic Disorders Induced by the Cafe Diet

The use of high-calorie nutrition can lead to morpho-functional changes of the vascular bed that have clinical importance, however, the modulatory effect of perivascular adipose tissue (PVAT) on the vascular system in this process remains poorly characterized. The aim of this work was to study the direct effect of PVAT on the contractile activity of rat aortic smooth muscle in metabolic disorders that occur when using the cafe diet (CD). It was shown that 7 weeks of keeping animals on this diet led to excessive accumulation of visceral adipose tissue, disorders of carbohydrate and lipid metabolism, manifested in the form of hyperglycemia and hypertriglyceridemia, which characterizes the development of the metabolic syndrome. An important functional role of PVAT in the regulation of vascular tone was demonstrated using wire myography on annular without endothelium segments of the thoracic aorta of the rat. In the control group of animals on a standard diet, the presence of PVAT reduced vasoconstriction caused by stimulation by phenylephrine. In the experimental group, in rats with the metabolic syndrome caused by DC, there was a decrease in the protective effect of PVAT. The implementation of this effect was carried out with the participation of voltage-dependent and/or Ca2+-activated K+-channels of smooth muscles, while the involvement of ATP-sensitive K+-channels was weak and independent from metabolic changes caused by the use of CD. Part of the anticontractile effect of PVAT was mediated through nitric oxide (NO) produced by PVAT itself. Under metabolic changes caused by CD, the endothelium-independent anticontractile effect of NO is completely eliminated without changing the sensitivity of vascular smooth muscles to it.

Causal relationship between gut microbiota with subcutaneous and visceral adipose tissue: a bidirectional two-sample Mendelian Randomization study.

Numerous studies have revealed associations between gut microbiota and adipose tissue. However, the specific functional bacterial taxa and their causal relationships with adipose tissue production in different regions of the body remain unclear. We conducted a bidirectional two-sample Mendelian Randomization (MR) study using aggregated data from genome-wide association studies (GWAS) for gut microbiota and adipose tissue. We employed methods such as inverse variance weighted (IVW), MR Egger, weighted median, simple mode, and weighted mode to assess the causal relationships between gut microbiota and subcutaneous adipose tissue (SAT) as well as visceral adipose tissue (VAT). Cochran's Q test, MR-Egger regression intercept analysis, and MR-PRESSO were used to test for heterogeneity, pleiotropy, and outliers of the instrumental variables, respectively. Reverse MR was employed to evaluate the reverse causal relationships between SAT, VAT, and gut microbiota with significant associations. IVW results demonstrated that Betaproteobacteria were protective factors for SAT production (OR = 0.88, 95% CI: 0.80-0.96, p = 0.005) and VAT production (OR = 0.91, 95% CI: 0.83-0.99, p = 0.030). Various bacterial taxa including Ruminococcaceae UCG002 (OR = 0.94, 95% CI: 0.89-0.99, p = 0.017), Methanobacteria class (OR = 0.96, 95% CI: 0.92-1.00, p = 0.029), and Burkholderiales (OR = 0.90, 95% CI: 0.83-0.98, p = 0.012) were associated only with decreased SAT production. Rikenellaceae RC9 gut group (OR = 1.05, 95% CI: 1.02-1.10, p = 0.005), Eubacterium hallii group (OR = 1.08, 95% CI: 1.01-1.15, p = 0.028), Peptococcaceae (OR = 1.08, 95% CI: 1.01-1.17, p = 0.034), and Peptococcus (OR = 1.05, 95% CI: 1.00-1.10, p = 0.047) were risk factors for SAT production. Meanwhile, Eubacterium fissicatena group (OR = 0.95, 95% CI: 0.91-0.99, p = 0.019), Turicibacter (OR = 0.93, 95% CI: 0.88-0.99, p = 0.022), and Defluviitaleaceae UCG011 (OR = 0.94, 95% CI: 0.89-0.99, p = 0.024) were protective factors for VAT production. Furthermore, Bacteroidetes (OR = 1.09, 95% CI: 1.01-1.17, p = 0.018), Eubacterium eligens group (OR = 1.09, 95% CI: 1.01-1.19, p = 0.037), Alloprevotella (OR = 1.05, 95% CI: 1.00-1.10, p = 0.038), and Phascolarctobacterium (OR = 1.07, 95% CI: 1.00-1.15, p = 0.042) were associated with VAT accumulation. Additionally, reverse MR revealed significant associations between SAT, VAT, and Rikenellaceae RC9 gut group (IVW: OR = 1.57, 95% CI: 1.18-2.09, p = 0.002) as well as Betaproteobacteria (IVW: OR = 1.14, 95% CI: 1.01-1.29, p = 0.029), both acting as risk factors. Sensitivity analyzes during bidirectional MR did not identify heterogeneity or pleiotropy. This study unveils complex causal relationships between gut microbiota and SAT/VAT, providing novel insights into the diagnostic and therapeutic potential of gut microbiota in obesity and related metabolic disorders.

Transcriptome-wide association study-derived genes as potential visceral adipose tissue-specific targets for type 2 diabetes.

This study aimed to assess the causal relationship between visceral obesity and type 2 diabetes and subsequently to screen visceral adipose tissue (VAT)-specific targets for type 2 diabetes. We examined the causal relationship between VAT and type 2 diabetes using bidirectional Mendelian randomisation (MR) followed by multivariable MR. We conducted a transcriptome-wide association study (TWAS) leveraging prediction models and a large-scale type 2 diabetes genome-wide association study (74,124 cases and 824,006 controls) to identify candidate genes in VAT and used summary-data-based MR (SMR) and co-localisation analysis to map causal genes. We performed enrichment and single-cell RNA-seq analyses to determine the cell-specific localisation of the TWAS-identified genes. We also conducted knockdown experiments in 3T3-L1 pre-adipocytes. MR analyses showed a causal relationship between genetically increased VAT mass and type 2 diabetes (inverse-variance weighted OR 2.48 [95% CI 2.21, 2.79]). Ten VAT-specific candidate genes were associated with type 2 diabetes after Bonferroni correction, including five causal genes supported by SMR and co-localisation: PABPC4 (1p34.3); CCNE2 (8q22.1); HAUS6 (9p22.1); CWF19L1 (10q24.31); and CCDC92 (12q24.31). Combined with enrichment analyses, clarifying cell-type specificity with single-cell RNA-seq data indicated that most TWAS-identified candidate genes appear more likely to be associated with adipocytes in VAT. Knockdown experiments suggested that Pabpc4 likely contributes to regulating differentiation and energy metabolism in 3T3-L1 adipocytes. Our findings provide new insights into the genetic basis and biological processes of the association between VAT accumulation and type 2 diabetes and warrant investigation through further functional studies to validate these VAT-specific candidate genes.

Visceral adipose tissue and residual cardiovascular risk: a pathological link and new therapeutic options.

Obesity is a heterogeneous disease that affects almost one-third of the global population. A clear association has been established between obesity and cardiovascular disease (CVD). However, CVD risk is known to be related more to the local distribution of fat than to total body fat. Visceral adipose tissue (VAT) in particular has a high impact on CVD risk. This manuscript reviews the role of VAT in residual CV risk and the available therapeutic strategies for decreasing residual CV risk related to VAT accumulation. Among the many pathways involved in residual CV risk, obesity and particularly VAT accumulation play a major role by generating low-grade systemic inflammation, which in turn has a high prognostic impact on all-cause mortality and myocardial infarction. In recent years, many therapeutic approaches have been developed to reduce body weight. Orlistat was shown to reduce both weight and VAT but has low tolerability and many drug-drug interactions. Naltrexone-bupropion combination lowers body weight but has frequent side effects and is contraindicated in patients with uncontrolled hypertension. Liraglutide and semaglutide, glucagon-like peptide 1 (GLP-1) agonists, are the latest drugs approved for the treatment of obesity, and both have been shown to induce significant body weight loss. Liraglutide, semaglutide and other GLP-1 agonists also showed a positive effect on CV outcomes in diabetic patients. In addition, liraglutide showed to specifically reduce VAT and inflammatory biomarkers in obese patients without diabetes. GLP-1 agonists are promising compounds to limit inflammation in human visceral adipocytes.

Visceral Adiposity Index as a Measure of Cardiovascular Disease in Persons With Human Immunodeficiency Virus.

Persons with well-treated human immunodeficiency virus (HIV) demonstrate a 2-fold higher risk of cardiovascular disease (CVD), which may be related to excess visceral adipose tissue (VAT). The visceral adiposity index (VAI) is a score to approximate VAT by combining biochemical measures with anthropometrics without quantification by imaging. We evaluated VAI in association with cardiometabolic factors among persons with HIV (PWH). Forty-five PWH on antiretroviral therapy and virologically controlled with increased abdominal VAT (VAT area >110 cm2 on CT) and no known CVD were included. VAI was calculated using standard sex-specific formulas. Coronary plaque was assessed using coronary CT angiography. Participants were predominantly male (73%), white (53%), and non-Hispanic (84%), with a mean age of 55 (standard deviation, 7) years. Among PWH, median VAI was calculated to be 4.9 (interquartile range [IQR], 2.8-7.3). Log VAI correlated with log VAT (r = 0.59, P < .0001) and anthropometric measures (body mass index: r = 0.36, P = .02; waist circumference: r = 0.43, P = .004; waist-to-hip ratio: r = 0.33, P = .03). Participants with coronary plaque had a higher VAI compared to those without coronary plaque (median, 5.3 [IQR, 3.4-10.5] vs 2.8 [IQR, 1.8-5.0]; P = .004). VAI (area under the curve = 0.760, P = .008) performed better than the atherosclerotic CVD risk score to predict the presence of plaque in receiver operating characteristic analyses. VAI may be a useful biomarker of metabolic dysfunction and increased CVD risk that may occur with VAT accumulation in PWH. NCT02740179.

Long-term aspartame and saccharin intakes are related to greater volumes of visceral, intermuscular, and subcutaneous adipose tissue: the CARDIA study

BackgroundArtificial sweetener (ArtSw) intakes have been previously associated with higher BMI in observational studies and may promote visceral and skeletal muscle adipose tissue (AT) accumulation. This study aimed to determine whether habitual, long-term ArtSw or diet beverage intakes are related to greater AT depot volumes and anthropometry-related outcomes.MethodsA validated diet history questionnaire was administered at baseline, year 7, and year 20 examinations in 3088 men and women enrolled in the Coronary Artery Risk Development in Young Adults cohort (CARDIA), mean age of 25.2 years and mean BMI of 24.5 kg/m2 at baseline. Volumes of visceral (VAT), intermuscular (IMAT), and subcutaneous adipose tissue (SAT) were assessed by computed tomography at year 25. Linear regression evaluated associations of aspartame, saccharin, sucralose, total ArtSw, and diet beverage intakes with AT volumes, anthropometric measures, and 25-year change in anthropometry. Cox regression estimated associations of ArtSw with obesity incidence. Adjustments were made for demographic and lifestyle factors, total energy intake, and the 2015 healthy eating index.ResultsTotal ArtSw, aspartame, saccharin, and diet beverage intakes were positively associated with VAT, SAT, and IMAT volumes (all ptrend ≤ 0.001), but no associations were observed for sucralose intake (all ptrend > 0.05). In addition, total ArtSw, saccharin, aspartame, and diet beverage intakes were associated with greater body mass index, body weight, waist circumference, and their increases over a 25-year period. Except for saccharin (ptrend = 0.13), ArtSw, including diet soda, was associated with greater risks of incident obesity over a median 17.5-year follow-up (all ptrend < 0.05).ConclusionsResults suggest that long-term intakes of aspartame, saccharin, or diet soda may increase AT deposition and risk of incident obesity independent of diet quality or caloric intake. Coupled with previous evidence, alternatives to national recommendations to replace added sugar with ArtSw should be considered since both may have health consequences.

31-OR: Sex-Specific Differences in Subcutaneous Adipose Tissue in Persons with HIV May Contribute to Diabetes Risk

Background: Men with HIV have greater visceral adipose tissue (VAT) accumulation compared to women, which contributes to insulin resistance and derives, in part, from a failure to sequester lipids in subcutaneous adipose tissue (SAT). We assessed whether sex-specific differences in SAT composition are associated with measures of VAT volume and insulin resistance. Methods: Adults with HIV and consistent viral suppression on antiretroviral therapy had SAT and VAT measured by CT imaging, HOMA2-IR using fasting plasma glucose and insulin, and a subset had abdominal SAT lipoaspirates for single-cell RNA-sequencing to define proportions of CD4 and CD8 T effector memory cells (TEM), perivascular (PVM) and intermediate (IM) macrophages, and fibroblasts. Adjusted ordinal regression models and partial Spearman’s assessed the interaction between sex and cell proportions. Results: We enrolled 111 participants (24% female) with a median age of 48 years, BMI of 31.5 kg/m2, and HOMA2-IR of 3.0. VAT volume was significantly associated with HOMA2-IR. Women had lower VAT volumes and higher proportions of SAT PVMs and lower IMs, as well as fewer cytotoxic CD4 and CD8 T cells compared with men (p ≤ 0.05 for all). The proportions of SAT CD4 TEM, CD8 TEM, myofibroblasts, MYOC fibroblasts, and IMs were associated with VAT volume (p ≤ 0.05 for all), but an interaction by sex was not observed. The proportions of CD4 and CD8 TEM cells were significantly associated with HOMA2-IR and there was evidence of an interaction by sex status (interaction term p = 0.09 &amp; p = 0.06, respectively). Conclusions: Women with HIV have a greater adjusted proportion of PVMs and lower cytotoxic CD4 and CD8 T cells in SAT. While the relationship between immune cell proportions and HOMA-IR only appeared to differ for CD4 and CD8 TEM cells, lower ectopic fat deposition in the context of reduced SAT inflammatory cells in women suggests the sex difference in diabetes risk among persons with HIV may relate to adipose tissue cellular composition. Disclosure S.Bailin: None. M.Mashayekhi: None. C.L.Gabriel: None. L.Hannah: None. S.Kalams: None. S.A.Mallal: None. J.A.Kropski: Advisory Panel; APIE Therapeutics, Research Support; Boehringer Ingelheim Inc., Bristol-Myers Squibb Company, Genentech, Inc. C.N.Wanjalla: None. J.Koethe: Advisory Panel; Merck Sharp &amp; Dohme Corp., Janssen Pharmaceuticals, Inc., Gilead Sciences, Inc., Theratechnologies, Research Support; Merck Sharp &amp; Dohme Corp. Funding National Institutes of Health (R01DK112262, UL1RR024975, T32AI007474, P30AI110527)

Molecular Mechanisms for the Vicious Cycle between Insulin Resistance and the Inflammatory Response in Obesity.

The comprehensive anabolic effects of insulin throughout the body, in addition to the control of glycemia, include ensuring lipid homeostasis and anti-inflammatory modulation, especially in adipose tissue (AT). The prevalence of obesity, defined as a body mass index (BMI) ≥ 30 kg/m2, has been increasing worldwide on a pandemic scale with accompanying syndemic health problems, including glucose intolerance, insulin resistance (IR), and diabetes. Impaired tissue sensitivity to insulin or IR paradoxically leads to diseases with an inflammatory component despite hyperinsulinemia. Therefore, an excess of visceral AT in obesity initiates chronic low-grade inflammatory conditions that interfere with insulin signaling via insulin receptors (INSRs). Moreover, in response to IR, hyperglycemia itself stimulates a primarily defensive inflammatory response associated with the subsequent release of numerous inflammatory cytokines and a real threat of organ function deterioration. In this review, all components of this vicious cycle are characterized with particular emphasis on the interplay between insulin signaling and both the innate and adaptive immune responses related to obesity. Increased visceral AT accumulation in obesity should be considered the main environmental factor responsible for the disruption in the epigenetic regulatory mechanisms in the immune system, resulting in autoimmunity and inflammation.

Abstract #1400837: Skewness in Body Fat Distribution Pattern Links to Specific Cardiometabolic Disease Risk Profiles

Research on body fat distribution illustrates a heterogeneity within obesity and indicates that the pattern in which a person carries their fat could help determine each individual’s cardiometabolic risk profile. The aim of this study was to evaluate the association between balance of different fat compartments (visceral, subcutaneous, and liver) with incident type 2 diabetes (T2D) and cardiovascular disease (CVD) in the UK Biobank imaging study. Magnetic resonance images were collected in 40,174 participants using a 6-minute neck-to-knee protocol and analyzed for visceral adipose tissue (VAT) volume, abdominal subcutaneous adipose tissue (aSAT) volume, and liver proton density fat fraction (LF) using AMRA® Researcher. To assess body fat distribution patterns independent of BMI, personalized body fat z-scores (VATz, aSATz, and LFz) were calculated for each participant using the distribution of least N=150 matched controls with the same sex and similar BMI. Participants without prevalent T2D and CVD (N=35,138), were partitioned in 3 ways: based on the balance between (1) VATz & LFz using z-scores=0 as cut-points (thus creating 4 groups: VATz< 0 & LFz< 0 (reference [lower VAT and LF than predicted by BMI]); VATz< 0 & LFz >0; VATz >0 & LFz< 0; VATz >0 & LFz >0, (2) VATz & aSATz, and (3) LFz & aSATz. Logistic regression and Cox proportional-hazards models were used to investigate the association of the balance between body fat z-scores with incident T2D and CVD respectively. Models were crude and subsequently adjusted for sex, age, and BMI. The strongest association with incident T2D were found for VATz >0 & LFz >0 (crude odds ratio (cOR) 4.31, 95% CI 2.83-6.78, p< 0.001), VATz >0 & aSATz< 0 (cOR 4.43, 95% CI 2.85-7.11, p< 0.001), and LFz >0 & aSATz< 0 (cOR 2.47, 95% CI 1.62-3.83, p< 0.001). When adjusted for sex, age, and BMI, those with VATz >0 and/or LFz >0 remained significant. For incident CVD, the strongest associations were found for VATz >0 & LFz< 0 (crude hazard ratio (cHR) 1.53, 95% CI 1.34-1.76, p< 0.001) and VATz >0 & aSATz< 0 (cHR 1.54, 95% CI 1.34-1.76, p< 0.001). When adjusted for sex, age, and BMI, only VATz >0 & LFz< 0 remained significant. Excessive accumulation of VAT in relation to BMI (VATz >0) was consistently linked to both T2D and CVD. Excessive accumulation of LF in relation to BMI (LFz >0) was linked to T2D only. Groups with skewed fat distribution patterns showed the highest risk for incident CVD (VATz >0 & LFz< 0 and VATz >0 & aSATz< 0) and T2D (VATz >0 & aSATz< 0). Descriptions of body fat distribution pattern could inform diagnosis and treatment strategies for obesity and related conditions.

Sleep traits, fat accumulation, and glycemic traits in relation to gastroesophageal reflux disease: A Mendelian randomization study.

Sleep traits, fat accumulation, and glycemic traits are associated with gastroesophageal reflux disease (GERD) in observational studies. However, whether their associations are causal remains unknown. We performed a Mendelian randomization (MR) study to determine these causal relationships. Independent genetic variants associated with insomnia, sleep duration, short sleep duration, body fat percentage, visceral adipose tissue (VAT) mass, type 2 diabetes, fasting glucose, and fasting insulin at the genome-wide significance level were selected as instrumental variables. Summary-level data for GERD were derived from a genome-wide association meta-analysis including 78,707 cases and 288,734 controls of European descent. Inverse variance weighted (IVW) was used for the main analysis, with weighted median and MR-Egger as complements to IVW. Sensitivity analyses were performed using Cochran's Q test, MR-Egger intercept test, and leave-one-out analysis to estimate the stability of the results. The MR study showed the causal relationships of genetically predicted insomnia (odds ratio [OR] = 1.306, 95% confidence interval [CI] 1.261 to 1.352; p = 2.24 × 10-51), short sleep duration (OR = 1.304, 95% CI: 1.147 to 1.483, p = 4.83 × 10-5), body fat percentage (OR = 1.793, 95% CI 1.496 to 2.149; p = 2.68 × 10-10), and visceral adipose tissue (OR = 2.090, 95% CI 1.963 to 2.225; p = 4.42 × 10-117) with the risk of GERD. There was little evidence for causal associations between genetically predicted glycemic traits and GERD. In multivariable analyses, genetically predicted VAT accumulation, insomnia, and decreased sleep duration were associated with an increased risk of GERD. This study suggests the possible roles of insomnia, short sleep, body fat percentage, and visceral adiposity in the development of GERD.

Visceral fat and attribute-based medicine in chronic kidney disease.

Visceral adipose tissue plays a central role in obesity and metabolic syndrome and is an independent risk factor for both cardiovascular and metabolic disorders. Increased visceral adipose tissue promotes adipokine dysregulation and insulin resistance, leading to several health issues, including systemic inflammation, oxidative stress, and activation of the renin-angiotensin-aldosterone system. Moreover, an increase in adipose tissue directly and indirectly affects the kidneys by increasing renal sodium reabsorption, causing glomerular hyperfiltration and hypertrophy, which leads to increased proteinuria and kidney fibrosis/dysfunction. Although the interest in the adverse effects of obesity on renal diseases has grown exponentially in recent years, the relationship between obesity and renal prognosis remains controversial. This may be attributed to the long clinical course of obesity, numerous obesity-related metabolic complications, and patients' attributes. Multiple individual attributes influencing the pathophysiology of fat accumulation make it difficult to understand obesity. In such cases, it may be effective to elucidate the pathophysiology by conducting research tailored to individual attributes from the perspective of attribute-based medicine/personalized medicine. We consider the appropriate use of clinical indicators necessary, according to attributes such as chronic kidney disease stage, level of visceral adipose tissue accumulation, age, and sex. Selecting treatments and clinical indicators based on individual attributes will allow for advancements in the clinical management of patients with obesity and chronic kidney disease. In the clinical setting of obesity-related nephropathy, it is first necessary to accumulate attribute-based studies resulting from the accurate evaluation of visceral fat accumulation to establish evidence for promoting personalized medicine.

Modulatory Effect of Fermented Black Soybean and Adlay on Gut Microbiota Contributes to Healthy Aging.

Aging is a natural process characterized by a multifactorial, physical decline, and functional disability. Nevertheless, healthy aging can be achieved by following a multidirectional strategy. The current study aims to investigate the anti-aging potential of fermented black soybean and adlay (FBA). FBA supplements are incorporated into a natural aging mouse model that is designed to evaluate anti-aging effects. Results show that FBA supplementation prevents muscle loss and visceral adipose tissue accumulation. FBA can also reduce aging biomarkers (including the expression of hepatic p16INK4A and galactosidase beta-1 (GLB1). Hepatic 8-hydoxy-2'-deoxyguanosine (8-oxodG) and pro-inflammatory cytokines have been significantly reduced. Lastly, FBA supplementation improves aging-related gut microbial dysbiosis by reshaping gut microbial composition and promoting the growth of beneficial microbes such as Alistipes, Anaeroplasma, Coriobacteriaceae UCG002, and Parvibacter members in both genders of aged mice. In the functional prediction of gut microbiota, correlations to metabolic, neurodegenerative, infectious, and immune system diseases have been reduced in supplemented mice compared to aged mice. Moreover, FBA supplementation can reverse the reduced ability of microbiota in aged mice for lipid metabolism and xenobiotics biodegradation. The results suggest that FBA exhibits noteworthy anti-aging effects and that it can potentially be developed into a functional food for healthy aging.

Hypertriglyceridemic waist phenotype is associated with left ventricular hypertrophy in Chinese hypertension patients

Left ventricular hypertrophy (LVH), the most common target organ damage in patients with hypertension, is closely related to excessive visceral adipose tissue (VAT) accumulation in the body. The hypertriglyceridemic waist (HTHW) phenotype can act as a surrogate marker of excessive VAT. However, the relationship between the HTHW phenotype and LVH in patients with hypertension remains unknown. The present study aimed to investigate whether the HTHW phenotype is associated with LVH, using echocardiography in a cross-sectional study involving 4470 middle-aged and older Chinese patients with hypertension. Logistic regression analysis revealed that patients with the HTHW phenotype were 1.52-fold more likely to experience LVH than those with normal triglyceride levels and normal waist circumference. This association was independent of age, sex, and other potentially confounding factors. In the stratified analysis, a stronger correlation was found among women, people of at least 70years of age, and people with hyperuricemia. These results suggest that distinguishing the HTHW phenotype in patients with hypertension could serve as a simple and effective screening strategy for identifying people with a higher risk of developing LVH.

Accumulation in Visceral Adipose Tissue Over 6 Years Is Associated With Lower Paraspinal Muscle Density.

Visceral adipose tissue (VAT) has been recognized to be a metabolically active fat depot that may have paracrine effects on surrounding tissues, including muscle. Since many adults accumulate VAT as they age, the effect of changes in VAT on muscle is of interest. We determined the association between 6-year changes in VAT and paraspinal muscle density, an indicator of fatty infiltration. This study included 1145 participants from the Framingham Study third-generation cohort who had both quantitative computed tomography scans of the spine at baseline and 6-year's follow-up, on whom muscle density was measured along with VAT. We implemented multiple regression to determine the association of muscle density at follow-up as primary outcome measure with changes in VAT (follow-up minus baseline divided by 100), adjusting for VAT at baseline, age, sex, height, menopausal status, presence of diabetes, and physical activity. Analyses were performed in men and women separately. After adjustment for covariates, individuals with the greatest accumulation of VAT over 6 years had significantly lower paraspinal density at the follow-up with an estimated 0.302 (95% CI, -0.380 to -0.224) and 0.476 (95% CI: -0.598 to -0.354) lower muscle density (HU) per 100-cm3 increase in VAT (both P values < .001) in men and women, respectively. These results highlight that age-related accumulation of VAT in men and women is associated with lower muscle density. VAT may represent a modifiable risk factor for poor musculoskeletal outcomes with aging.

Association between Blood Manganese Levels and Visceral Adipose Tissue in the United States: A Population-Based Study.

Manganese (Mn) is an essential trace element with a narrow toxic margin for human health. The association between Mn exposure and adverse visceral adipose tissue (VAT) accumulation is unclear. This study aimed to estimate the associations of blood Mn levels with VAT mass or visceral obesity in the general population in the United States. This cross-sectional study included data of 7297 individuals released by National Health and Nutrition Examination Survey (NHANES). VAT was quantified with dual-energy X-ray absorptiometry, and blood Mn was measured using inductively coupled plasma mass spectrometry. The generalized linear model and generalized additive model (GAM) were applied to estimate the linear and non-linear associations between Mn levels and VAT mass, respectively. Logistic regression was used to estimate the associations between blood Mn levels and the risk of visceral obesity. Fully adjusted generalized linear regression revealed that individuals in the higher quantile of Mn had increased VAT mass compared with those in the lower quantile (β per quantile change = 0.025; 95% CI of 0.017, 0.033; p &lt; 0.001). Positive associations were also observed in males and females (males: β per quantile change = 0.012, 95% CI of 0.002, 0.022 (p = 0.020); female: β per quantile change = 0.036; 95% CI of 0.023, 0.048 (p &lt; 0.001)). The GAM illustrated that the non-linear associations between blood Mn levels and VAT mass were in U-shape patterns (effective degree of freedom &gt;1 in total participants, males, and females). A stratified analysis found significant interactions between Mn and the family income-to-poverty ratio (PIR) in males, with stronger associations in males with a PIR &lt; 1.3 (β = 0.109; 95% CI of 0.048, 0.170). Additional analyses revealed that individuals in the highest quantile of Mn had a 39% higher risk of visceral obesity (OR = 1.39; 95% CI of 1.15-1.69; p &lt; 0.001). Higher blood Mn levels were positively associated with increased VAT mass and visceral obesity risk. The adverse VAT phenotype associated with excessive blood Mn levels should be further investigated.

RF12 | PSUN104 Visceral adiposity index as a measure of cardiometabolic disease in persons living with HIV

Abstract Well-treated persons living with HIV (PLWH) are predisposed to fat redistribution/visceral adiposity, potentially due to anti-retroviral therapy (ART) use and/or the virus itself, and demonstrate a 2-fold higher risk of cardiovascular disease (CVD) compared to those without HIV. Visceral adipose tissue (VAT) is a metabolically unfavorable ectopic fat depot, which is highly inflamed and dysfunctional. Fat redistribution leading to VAT accumulation is related to increased CVD risk. Current gold standard measures of VAT are obtained using CT and MRI, but are not used clinically. The visceral adiposity index (VAI) is a simple tool combining biochemical measures with anthropometrics that can be easily evaluated by the clinician. VAI may be a surrogate measure of VAT and indeed has been shown to relate to insulin resistance, type 2 diabetes mellitus, metabolic syndrome and CVD among the general population. In this study, we evaluated VAI in PLWH and its relation to VAT, anthropometric measures and other cardiometabolic parameters. 45 PLWH on stable ART with no known CVD were recruited as part of a clinical trial to evaluate CVD indices and were included if they were virologically controlled (HIV viral load &amp;lt;200 copies/mL) and demonstrated increased abdominal VAT (VAT area&amp;gt;110cm2) on CT. For purposes of this study, baseline fasting biochemical, radiologic and anthropometric data were used. VAI was calculated using the standard sex-specific formulas which incorporate waist circumference (WC), BMI, triglycerides and HDL. Presence of coronary plaque was assessed using coronary CT angiography or coronary PET scans. Linear regression was performed to assess relationships with VAI. Non-normally distributed variables were log-transformed for analyses. Participants were predominantly male (73%), Caucasian (53%), and non-Hispanic (84%) with mean age 55 ± 7 years. Participants had a long duration of HIV and ART use (20 ± 8 and 15 [12,19] years, respectively). The majority of PLWH were obese (BMI 31.9 ± 5.8 kg/m2) with VAT 189 [127,267]cm2 and VAI 4.9 [2.8,7.3]. VAI correlated strongly with VAT (r=0.59, P&amp;lt;0.0001), anthropometric measures (BMI r=0.36, P=0.02; WC r=0.43, P=0.004; WHR r=0.33, P=0.03) and ALT (r=0.32, P=0.03), and did not relate to HIV-specific parameters and other metabolic parameters (blood pressure, HbA1c). Participants with coronary plaque tended to have a higher VAI compared to those without coronary plaque (log VAI 0.7 ± 0.3 vs. 0.5 ± 0.3, P=0.056). These data show VAI, an easily obtained measure, is strongly correlated with abdominal VAT area measured by CT and may be a useful biomarker for visceral adiposity in HIV. Furthermore, VAI may be related to ALT and coronary plaque, which could help identify those PLWH at risk for fatty liver disease (another ectopic fat depot) and heart disease, respectively. Further studies are needed to assess the utility of VAI in evaluating metabolic disease in HIV. Presentation: Saturday, June 11, 2022 1:24 p.m. - 1:29 p.m., Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.

The influence of perinatal maternal exposure to dibutyl phthalate on glucolipid metabolism in adult female offspring

BackgroundMaternal exposure to dibutyl phthalate (DBP) may result in obesity in female offspring. However, the underlying mechanisms remain elusive. Materials and methodsSprague-Dawley rats were intraperitoneally injected with different doses of DBP and corn oil from gestational day 7 until the end of lactation. The weights, visceral fat percentage, serum lipid, insulin and glucose, protein levels of PI3K signal pathway in muscle were detected in F1 female offspring. ResultsAlthough the birth weight of F1 female offspring was not different among groups, the weights were heavier in DBP groups from postnatal day 7 to adult (P < 0.001). The visceral adipose percentage in adult female offspring was increased by perinatal exposure to DBP (P < 0.001). Decreased serum level of triglyceride (P = 0.001) in F1 female offspring was found in DBP group as compared to control, especially in medium and high DBP. However, none difference was found for fasting glucose, prolactin, HOMA-IR, fasting insulin, total cholesterol, adiponectin. Different protein levels of GPR30 were observed in muscle of female offspring among four groups (P = 0.016). The protein level of AKT seemed higher in DBP group but without statistical significance (P = 0.05). None difference was observed for the protein levels of PI3K, p-AKT, pAKT/AKT, PTEN, GLUT4, InsR, IRS. ConclusionMaternal perinatal exposure to DBP might induce obesity and accumulation of visceral adipose tissue for the adult female offspring. Serum glucolipid and local signal transduction of PTEN/PI3K/AKT pathway in muscle were not adversely affected by perinatal exposure to DBP for adult female offspring.

Extended treatment with (1→3)(1→6)-β-d-glucan (Botryosphaeran) reduces obesity and its comorbidities in high-fat/high-sugar diet-fed rats.

Obesity is associated with other diseases such as diabetes and cancer. Botryosphaeran, a fungal (1→3)(1→6)-β-d-glucan, is described to present antimutagenic, hypoglycemic, hypocholesterolemic, and antitumor activities when administered by gavage over 15 days in rats and mice. Thus, the present study aims to analyze the metabolic effects of Botryosphaeran (12 mg/kg body weight/day) treatment over 30 days in obese Wistar male rats. Obesity was induced in the rats by a high-fat/high-sugar diet for 8 weeks. Control rats received a standard diet. On the5th week, Botryosphaeran treatment commenced. Groups: control, obese, and obese+Botryosphaeran 30 days. In the8th week, obesity was characterized. Feed intake, glucose and lipid profiles, glucose tolerance, and insulin sensitivity were analyzed. Obese rats showed accumulation of visceral adipose tissue, reduction of muscle mass, glucose intolerance, insulin resistance, hyperglycemia, and dyslipidemia. Botryosphaeran effectively reduced weight gains and the accumulation of retroperitoneal adipose tissue, corrected the levels of glucose, triglycerides, and very low-density lipoprotein-cholestrol, and improved insulin sensitivity. Treatment for 30 days was effective in maintaining the beneficial effects demonstrated by this β-glucan when administered for 15 days without promoting side effects. Treatment with (1→3)(1→6)-β- d-glucan presented anti-obesogenic and beneficial metabolic effects in Wistar rats; important for the treatment of obesity and its comorbidities.

Growth Hormone Secretory Capacity Is Associated with Cardiac Morphology and Function in Overweight and Obese Patients: A Controlled, Cross-Sectional Study.

Obesity is associated with increased cardiovascular morbidity. Adult patients with growth hormone deficiency (GHD) show morpho-functional cardiological alterations. A total of 353 overweight/obese patients are enrolled in the period between 2009 and 2019 to assess the relationships between GH secretory capacity and the metabolic phenotype, cardiovascular risk factors, body composition and cardiac echocardiographic parameters. All patients underwent GHRH + arginine test to evaluate GH secretory capacity, DEXA for body composition assessment and transthoracic echocardiography. Blood samples are also collected for the evaluation of metabolic parameters. In total, 144 patients had GH deficiency and 209 patients had normal GH secretion. In comparing the two groups, we found significant differences in body fat distribution with predominantly visceral adipose tissue accumulation in GHD patients. Metabolic syndrome is more prevalent in the GHD group. In particular, fasting glycemia, triglycerides and systolic and diastolic blood pressure are found to be linearly correlated with GH secretory capacity. Epicardial fat thickness, E/A ratio and indexed ventricular mass are worse in the GHD group. In the population studied, metabolic phenotype, body composition, cardiovascular risk factors and cardiac morphology are found to be related to the GH secretory capacity. GH secretion in the obese patient seems to be an important determinant of metabolic health.