Exercise-induced changes in left ventricular strain are affected by interleukin-6 activity: An exploratory analysis of a randomised-controlled trial in humans with abdominal obesity.

Whilst the exercise-induced myokine interleukin-6 (IL-6) plays a beneficial role in cardiac structural adaptations, its influence on exercise-induced functional cardiac outcomes remains unknown. We hypothesised that IL-6 activity is required for exercise-induced improvements in left ventricular global longitudinal strain (LV GLS). In an exploratory study 52 individuals with abdominal obesity were randomised to 12 weeks' high-intensity exercise or no exercise in combination with IL-6 receptor inhibition (IL-6i) or placebo. LV strain and volume measurements were assessed by cardiac magnetic resonance. Exercise improved LV GLS by -5.4% [95% CI: -9.1% to -1.6%] (P = 0.007). Comparing the change from baseline in LV GLS in the exercise + placebo group (-4.8% [95% CI: -7.4% to -2.2%]; P < 0.0004) to the exercise + IL-6i group (-1.1% [95% CI: -3.8% to 1.6%]; P = 0.42), the exercise + placebo group changed -3.7% [95% CI: -7.4% to -0.02%] (P = 0.049) more than the exercise + IL6i group. However, the interaction effect between exercise and IL-6i was insignificant (4.5% [95% CI: -0.8% to 9.9%]; P = 0.09). Similarly, the exercise + placebo group improved LV global circumferential strain by -3.1% [95% CI: -6.0% to -0.1%] (P = 0.04) more compared to the exercise + IL-6i group, yet we found an insignificant interaction between exercise and IL-6i (4.2% [95% CI: -1.8% to 10.3%]; P = 0.16). There was no effect of IL-6i on exercise-induced changes to volume rates. This study underscores the importance of IL-6 in improving LV GLS in individuals with abdominal obesity suggesting a role for IL-6 in cardiac functional exercise adaptations.

Visceral adiposity associated with incidence and development trajectory of cardiometabolic diseases: A prospective cohort study.

BACKGROUND AND AIMS: There is a lack of literature concerning the effects of visceral adipose on the development of first cardiometabolic disease (FCMD) and its subsequent progression to cardiometabolic multimorbidity (CMM) and mortality. METHODS AND RESULTS: 423,934 participants from the UK Biobank with different baseline disease conditions were included in the analysis. CMM was defined as the simultaneous presence of coronary heart disease, T2D, and stroke. Visceral adiposity was estimated by calculating the visceral adiposity index (VAI). Multistate models were used to assess the effect of visceral adiposity on the development of CMM. During a median follow-up of 13.5 years, 50,589 patients had at least one CMD, 6131 were diagnosed with CMM, whereas 24,634 patients died. We observed distinct roles of VAI with respect to different disease transitions of CMM. HRs (95 % CIs) of high VAI were 2.35 (2.29-2.42) and 1.64 (1.50-1.79) for transitions from healthy to FCMD and from FCMD to CMM, and 0.97 (0.93-1.02) for all-cause mortality risk from healthy, FCMD and CMM, respectively. CONCLUSIONS: Our study provides the first evidence that visceral adipose may contribute to the development of FCMD and CMM in healthy participants. However, visceral adipose may confer resistance to all-cause mortality in participants with existing CMD or CMM. A better understanding of the relationship between visceral adipose and CMM can focalize further investigations on patients with CMD with high levels of visceral fat and help take targeted preventive measures to reduce the medical burden on individual patients and society.

Association between obstructive sleep apnea and visceral adiposity index and lipid accumulation product: NHANES 2015-2018.

BACKGROUND: Obesity refers to a significant contributor to the development of obstructive sleep apnea (OSA). Early prediction of OSA usually leads to better treatment outcomes, and this study aims to employ novel metabolic markers, visceral adiposity index (VAI), and lipid accumulation product (LAP) to evaluate the relationship to OSA. METHODS: The data used in the current cross-sectional investigation are from the National Health and Nutrition Examination Survey (NHANES), which was carried out between 2015 and 2018. To examine the correlation between LAP and VAI levels and OSA, multivariate logistic regression analysis was adopted. In addition, various analytical methods were applied, including subgroup analysis, smooth curve fitting, and threshold effect analysis. RESULTS: Among totally 3932 participants, 1934 were included in the OSA group. The median (Q1-Q3) values of LAP and VAI for the participants were 40.25 (21.51-68.26) and 1.27 (0.75-2.21), respectively. Logistic regression studies indicated a positive correlation between LAP, VAI, and OSA risk after adjusting for potential confounding variables. Subgroup analysis revealed a stronger correlation between LAP, VAI levels, and OSA among individuals aged < 60 years. Through smooth curve fitting, specific saturation effects of LAP, VAI, and BMD were identified, with inflection points at 65.684 and 0.428, respectively. CONCLUSION: This study demonstrates that elevated levels of LAP and VAI increase the risk of OSA, suggesting their potential as predictive markers for OSA and advocating for dietary and exercise interventions to mitigate OSA risk in individuals with high LAP and VAI levels.

The visceral adipose tissue bacterial microbiota provides a signature of obesity based on inferred metagenomic functions.

BACKGROUND: Metabolic inflammation mediated obesity requires bacterial molecules to trigger immune and adipose cells leading to inflammation and adipose depot development. In addition to the well-established gut microbiota dysbiosis, a leaky gut has been identified in patients with obesity and animal models, characterized by the presence of a tissue microbiota in the adipose fat pads. METHODS: To determine its potential role, we sequenced the bacterial 16 S rRNA genes in the visceral adipose depot of patients with obesity. Taking great care (surgical, biochemical, and bioinformatic) to avoid environmental contaminants. We performed statistical discriminant analyses to identify specific signatures and constructed network of interactions between variables. RESULTS: The data showed that a specific 16SrRNA gene signature was composed of numerous bacterial families discriminating between lean versus patients with obesity and people with severe obesity. The main discriminant families were Burkholderiaceae, Yearsiniaceae, and Xanthomonadaceae, all of which were gram-negative. Interestingly, the Morganellaceae were totally absent from people without obesity while preponderant in all in patients with obesity. To generate hypotheses regarding their potential role, we inferred metabolic pathways from the 16SrRNA gene signatures. We identified several pathways associated with adenosyl-cobalamine previously described to be linked with adipose tissue development. We further identified chorismate biosynthesis, which is involved in aromatic amino-acid metabolism and could play a role in fat pad development. This innovative approach generates novel hypotheses regarding the gut to adipose tissue axis. CONCLUSIONS: This innovative approach generates novel hypotheses regarding the gut to adipose tissue axis in obesity and notably the potential role of tissue microbiota.

Cumulative burden of abnormal visceral adiposity index and its components on the risk of hyperuricemia.

BACKGROUND AND AIMS: The visceral adiposity index (VAI), a gender-specific surrogate maker of adipose tissue distribution and function, is associated with risk of hyperuricemia. However, the impact of time-burden of abnormal VAI and its components on the risk of hyperuricemia remains unknown. METHODS AND RESULTS: We included 56,537 participants without hyperuricemia and underwent two health examinations during 2006-2008 from the Kailuan study. Abnormal VAI burdens were evaluated as follows: (1) cumulative number of abnormal VAI presented at each examination (0-2 times); (2) cumulative number of each abnormal VAI component presented at each examination (0-2 times per component); (3) cumulative number of total abnormal VAI components presented at each examination (0-8 times). During a median follow-up of 8.81 years, 10,762 participants were diagnosed with hyperuricemia. The risk of hyperuricemia showed a positive association with cumulative number of abnormal VAI, the adjusted hazard ratio (HR) with 95% confidence interval (CI) of 2 times compared to 0 times was 1.69 (1.58-1.81). All four components of abnormal VAI, when diagnosed repeatedly, were independently associated with an increased risk of hyperuricemia, adjusted HR (95% CI) from 1.15 (1.02-1.28) for low high-density lipoprotein to 1.68 (1.58-1.79) for elevated triglyceride. The risk of hyperuricemia also gradually as abnormal components was accumulated from 0 to 8 counts, reaching an adjusted HR (95% CI) of 3.72 (2.64-5.23). Furthermore, the effect of cumulative abnormal VAI was more pronounced in females than males (P-interaction < 0.0001). CONCLUSIONS: Cumulative abnormal VAI burdens were positively associated with the risk of hyperuricemia, especially in females.

Visceral Obesity and Cytokeratin-18 Antigens as Early Biomarkers of Liver Damage.

Visceral obesity is linked to the progression of fatty liver to nonalcoholic steatohepatitis (NASH). Cytokeratin-18 (CK18) epitopes M30 (CK18M30) and M65 (CK18M65) represent accurate markers for detecting NASH. The aim of this study was to evaluate the association of CK18M30 and CK18M65 levels with anthropometric and metabolic characteristics, liver stiffness, and liver indices of steatosis and fibrosis in a cohort of subjects with visceral obesity; in this cross-sectional study, transient elastography (TE-Fibroscan®), anthropometric measurements, metabolic parameters, High Sensitivity C-Reactive Protein (hsCRP), and CK18M30 and CK18M65 levels (Apoptosense ELISA, PEVIVA, Germany) were evaluated. Fatty Liver Index (FLI), Fibrosis 4 (FIB-4), and Aspartate transaminase (AST)-platelet ratio index (APRI) were calculated; among 48 subjects, 47.2% presented metabolic syndrome, 93.8% hepatic steatosis, 60.4% high liver stiffness, and 14.6% hypertransminasemia, while FIB-4 and APRI were normal. CK18M30 and CK18M65 levels were significantly correlated with waist circumference, AST, ALT, HoMA-IR, liver stiffness, and APRI (p < 0.001). Subjects with CK18 fragments above the median values showed significantly higher waist circumference, HbA1c, AST, ALT, HoMA-IR, FLI, and APRI compared to those with values below the median; CK18M30 and CK18M65 levels correlated well with anthropometric and metabolic characteristics, representing good biomarkers for early identification of NASH in subjects with visceral obesity.

Hepatic-Specific FGF21 Knockout Abrogates Ovariectomy-Induced Obesity by Reversing Corticosterone Production.

Increased glucocorticoid (GC) levels act as a master contributor to central obesity in estrogen-depleted females; however, what factors cause their increased GC production is unclear. Given (1) liver fibroblast growth factor 21 (FGF21) and GCs regulate each other's production in a feed-forward loop, and (2) circulating FGF21 and GCs are parallelly increased in menopausal women and ovariectomized mice, we thus hypothesized that elevation of hepatic FGF21 secretion causes increased GGs production in estrogen-depleted females. Using the ovariectomized mice as a model for menopausal women, we found that ovariectomy (OVX) increased circulating corticosterone levels, which in turn increased visceral adipose Hsd11b1 expression, thus causing visceral obesity in females. In contrast, liver-specific FGF21 knockout (FGF21 LKO) completely reversed OVX-induced high GCs and high visceral adipose Hsd11b1 expression, thus abrogating OVX-induced obesity in females. Even though FGF21 LKO failed to rescue OVX-induced dyslipidemia, hepatic steatosis, and insulin resistance. What's worse, FGF21 LKO even further exacerbated whole-body glucose metabolic dysfunction as evidenced by more impaired glucose and pyruvate tolerance and worsened insulin resistance. Mechanically, we found that FGF21 LKO reduced circulating insulin levels, thus causing the dissociation between decreased central obesity and the improvement of obesity-related metabolic syndromes in OVX mice. Collectively, our results suggest that liver FGF21 plays an essential role in mediating OVX-induced central obesity by promoting GC production. However, lack of liver FGF21 signaling reduces insulin production and in turn causes the dissociation between decreased central obesity and the improvement of obesity-related metabolic syndromes, highlighting a detrimental role for hepatic FGF21 signals in mediating the development of central obesity but a beneficial role in preventing metabolic abnormality from further exacerbation in estrogen-depleted females.

The metabolic triad of non-alcoholic fatty liver disease, visceral adiposity and type 2 diabetes: Implications for treatment.

Non-alcoholic fatty liver disease (NAFLD) is associated with visceral obesity, insulin resistance, type 2 diabetes (T2D) and has been often considered as the hepatic expression of the metabolic syndrome (MetS). Epidemiological studies highlight a bidirectional relationship of NAFLD with T2D in which NAFLD increases the risk of incident T2D and T2D increases the risk of severe non-alcoholic steatohepatitis (NASH) and liver fibrosis. Regarding the molecular determinants of NAFLD, we specifically focused in this review on adipocyte dysfunction as a key molecular link between visceral adipose tissue, MetS and NAFLD. Notably, the subcutaneous white adipose tissue expandability appears a critical adaptive buffering mechanism to prevent lipotoxicity and its related metabolic complications, such as NAFLD and T2D. There is a clinical challenge to consider therapeutic strategies targeting the metabolic dysfunction common to NASH and T2D pathogenesis. Strategies that promote significant and sustained weight loss (~10% of total body weight) such as metabolic and bariatric surgery or incretin-based therapies (GLP-1 receptor agonists or dual GLP-1/GIP or GLP-1/glucagon receptor co-agonists) are among the most efficient ones. In addition, insulin sensitizers such as PPARγ (pioglitazone) and pan-PPARs agonists (lanifibranor) have shown some beneficial effects on both NASH and liver fibrosis. Since NASH is a complex and multifactorial disease, it is conceivable that targeting different pathways, not only insulin resistance but also inflammation and fibrotic processes, is required to achieve NASH resolution.

Interaction of MC4R rs17782313 variants and dietary carbohydrate quantity and quality on basal metabolic rate and general and central obesity in overweight/obese women: a cross-sectional study.

BACKGROUND: Recent studies have shown that dietary carbohydrate quantity and quality as well as genetic variants may contribute to determining the metabolic rate and general and central obesity. This study aimed to examine interactions between melanocortin 4 receptor gene (MC4R) rs17782313 and dietary carbohydrate intake, glycemic index (GI), and glycemic load (GL) on body mass index (BMI), waist circumferences (WC), basal metabolic rate (BMR), and BMR/kg in overweight/obese women. METHODS: A total of 282 Iranian women (BMI ≥ 25) aged 18-56 years were enrolled in this cross-sectional study. All participants were assessed for blood parameters, body composition, BMR, and dietary intake. Dietary carbohydrate intake, GI, and GL were determined using a valid, reliable 147-item food frequency questionnaire. MC4R rs17782313 was genotyped by the restriction fragment length polymorphism (PCR-RFLP) method. RESULTS: After adjustment for age and energy intake, significant interactions were observed between carbohydrate intake and MC4R rs17782313 in terms of BMI (P Interaction = 0.007), WC (P Interaction = 0.02), and BMR/kg (P Interaction = 0.003) in this way that higher carbohydrate intake, compared with lower intake, was associated with an increase in BMI and WC for individuals with C allele carriers (TC + CC genotypes), while related to an increase in BMR/kg for those carrying the TT genotype. No significant interaction was found between MC4R rs17782313 and GI and GL on BMI, WC, BMR/kg, and BMR. CONCLUSIONS: Interactions between the MC4R rs17782313 and carbohydrate intake probably can have an effect on BMI, WC, and BMR/kg in overweight/obese women.

DXA-Derived vs Standard Anthropometric Measures for Predicting Cardiometabolic Risk in Middle-Aged Australian Men and Women.

It is not clear if dual-energy X-ray absorptiometry (DXA) adiposity measures are superior to standard anthropometric measures for predicting cardiometabolic (CM) risk factors in a middle-aged general population. In the Busselton Healthy Ageing Study, we assessed a range of standard anthropometric and DXA-derived adiposity measures to predict metabolic syndrome (MetS) and CM risk factors in 4831 "baby boomers" aged 45-69 yr. Anthropometric and whole body DXA (GE Lunar Prodigy) measures were collected. Cross-sectional relationships of overall adiposity (BMI; DXA fat mass index, body fat %), central adiposity (waist circumference (WC); DXA trunk fat, android fat, abdominal visceral adipose tissue (VAT)) and ratio index (waist-to-hip ratio; DXA trunk/legs fat, android/gynoid ratio, VAT/total fat) with MetS and its components (as both continuous and binary outcomes) were evaluated using linear and logistic regression adjusting for age and lifestyle factors. Youden's Index was used to determine the optimal cut-points for predicting MetS. In linear regression analyses, central adiposity measures showed stronger associations with MetS score and CM risk factors than overall adiposity measures and fat ratio index, and DXA-VAT provided stronger associations than WC. Logistic regression models showed similar findings. For MetS diagnosis present in 35.9% of males and 24.4% of females, the highest odds ratio (95% CI) per SD change was observed for DXA-VAT (males: 5.02 [4.28, 5.88]; females: 3.91 [3.40, 4.49]), which remained significant (all p < 0.001) after further adjustment for BMI (males: 3.27 [2.65, 4.02]; females: 3.37 [2.79, 4.06]) or WC (males: 2.46 [1.95, 3.10]; females: 2.75 [2.21, 3.43]). The optimal DXA-VAT mass cut-point for predicting MetS was 1608 grams in males and 893 grams in females. DXA-VAT was superior to standard anthropometric and other DXA-derived adiposity measures for prediction of cardiometabolic risk factors, and has clinical utility for identifying middle-aged individuals at increased risk of MetS.

Diagnostic accuracy of the visceral adiposity index in patients with metabolic-associated fatty liver disease: a meta-analysis.

BACKGROUND: Conflicting results on the prognostic value of the visceral adiposity index (VAI) in patients with metabolic-associated fatty liver disease (MAFLD) have been reported. This study aimed to assess the diagnostic value of the VAI in MAFLD patients. METHODS: The Cochrane Library, PubMed, Embase, and other databases were searched to collect all documents that met the inclusion criteria from the establishment of the database to September 2021. The methodological quality of the included studies was assessed using the Newcastle-Ottawa Scale. The heterogeneity among the studies was analysed by the Cochran Q test and I2 test, and the appropriate model was selected according to the heterogeneity results. The diagnostic efficacy of the VAI was evaluated by sensitivity, specificity, and area under the curve, and a Fagan diagram was generated to evaluate the diagnostic ability of the VAI. RESULTS: A total of 9 studies were included. The overall quality of the included studies was good. Meta-analysis showed that the combined sensitivity of the VAI for the diagnosis of MAFLD was 0.70 [95% CI (0.69-0.71)], the combined specificity was 0.67 [95% CI (0.67-0.68)], the combined positive likelihood ratio was 2.08 [95% CI (1.87-2.31)], the combined negative likelihood ratio was 0.39 [95% CI (0.34-0.44)], and the combined diagnostic odds ratio was 5.81 [95% CI (4.73-7.14)]. The corresponding area under the curve was 0.79 [95% CI (0.75-0.82)]. Meta-regression analysis showed that the diagnostic method was a potential source of heterogeneity (P < 0.05). The Fagan diagram showed that the precision of MAFLD diagnosis was 70% when the pretest probability was set to 50% and then supplemented by the VAI. CONCLUSIONS: The VAI is an independent predictor in the diagnosis of MAFLD and may be helpful in the detection of MAFLD. A VAI > 2.33 suggests that patients have a high probability of having MAFLD.

Biological Determinants of Metabolic Syndrome in Visceral and Subcutaneous Adipose Tissue from Severely Obese Women.

The metabolic syndrome (MetS) is a cluster of the most dangerous heart attack risk factors: diabetes or raised fasting plasma glucose, abdominal obesity, high cholesterol and high blood pressure. The goal of this study is to compare the state of the main features of obesity-associated white adipose tissue (WAT) dysfunction in 66 women with severe obesity without (MetS-) or with MetS (MetS+). Fat cell area, adipocyte size distribution and histological fibrosis were analysed in visceral (VAT) and abdominal subcutaneous WAT (SAT) in 33 age- and BMI-matched pairs of MetS- and MetS+ subjects. The mRNA expression of 93 genes implicated in obesity-associated WAT dysfunction was analysed by RT-qPCR in both fat depots. MetS+ females showed higher adipocyte hypertrophy in both fat depots and increased fibrosis and expression of macrophage and hypoxia markers in SAT. Transcriptional data suggest increased fatty acid oxidation in SAT and impaired thermogenesis and extracellular matrix remodelling in VAT from MetS+ subjects. A sPLS-DA model, including SAT expression of PPARA and LEPR genes identified MetS with an AUC = 0.87. Despite equal age, BMI and body composition, MetS+ females display morphological and transcriptional differences in both WAT depots, especially in SAT. These factors may contribute to the transition to MetS.

Effects of Central Obesity on Esophageal Epithelial Barrier Function.

INTRODUCTION: We assessed if obesity perturbs the esophageal epithelial barrier function independent of promotion of gastroesophageal reflux (GER). METHODS: Thirty-eight participants were divided into 4 groups: Obesity-/GER-, Obesity+/GER-, Obesity-/GER+, and Obesity+/GER+. Esophageal intercellular space and desmosome density (structural integrity) and fluorescein leak (functional integrity) were measured. RESULTS: The Obesity+/GER- group demonstrated increased intercellular space, reduced desmosome density, and increased fluorescein leak compared with control subjects. These changes were similar but not additive to findings seen in Obesity-/GER + and Obesity+/GER+ patients. DISCUSSION: Central obesity impairs structural and functional integrity of the esophageal barrier independent of GER, likely predisposing to esophageal injury.

Metabolite patterns link diet, obesity, and type 2 diabetes in a Hispanic population.

INTRODUCTION: Obesity is a precursor of type 2 diabetes (T2D). OBJECTIVES: Our aim was to identify metabolic signatures of T2D and dietary factors unique to obesity. METHODS: We examined a subsample of the Boston Puerto Rican Health Study (BPRHS) population with a high prevalence of obesity and T2D at baseline (n = 806) and participants (without T2D at baseline) at 5-year follow-up (n = 412). We determined differences in metabolite profiles between T2D and non-T2D participants of the whole sample and according to abdominal obesity status. Enrichment analysis was performed to identify metabolic pathways that were over-represented by metabolites that differed between T2D and non-T2D participants. T2D-associated metabolites unique to obesity were examined for correlation with dietary food groups to understand metabolic links between dietary intake and T2D risk. False Discovery Rate method was used to correct for multiple testing. RESULTS: Of 526 targeted metabolites, 179 differed between T2D and non-T2D in the whole sample, 64 in non-obese participants and 120 unique to participants with abdominal obesity. Twenty-four of 120 metabolites were replicated and were associated with T2D incidence at 5-year follow-up. Enrichment analysis pointed to three metabolic pathways that were overrepresented in obesity-associated T2D: phosphatidylethanolamine (PE), long-chain fatty acids, and glutamate metabolism. Elevated intakes of three food groups, energy-dense takeout food, dairy intake and sugar-sweetened beverages, associated with 13 metabolites represented by the three pathways. CONCLUSION: Metabolic signatures of lipid and glutamate metabolism link obesity to T2D, in parallel with increased intake of dairy and sugar-sweetened beverages, thereby providing insight into the relationship between dietary habits and T2D risk.

Selenium status and oxidative stress in obese: Influence of adiposity.

BACKGROUND: Selenium deficiency appears to limit antioxidant defense in obese individuals. This study evaluated the association between adiposity indices, selenium status, and oxidative stress in obese women. METHODS: This was a cross-sectional study involving 139 women who were divided into the following two groups: the case group (obese women, n = 63) and the control group (normal-weight women, n = 76). Plasma, erythrocyte, and urinary selenium levels were determined using inductively coupled plasma optical emission spectrometry. Body weight, height, waist circumference, hip circumference and neck circumference were measured. Body mass index, waist/height ratio, conicity index, body fat index, body adiposity index, body circularity index, and visceral adiposity index were calculated. Plasma levels of thiobarbituric acid reactive substances were determined. The erythrocyte glutathione peroxidase activity was determined using an automatic biochemical analyzer and Ransel kit. RESULTS: Obese women had selenium deficiency characterized by reduction in plasma and erythrocyte concentrations (P < .001). The urinary selenium excretion was higher in the case group compared to the control group (P < .001). Adiposity indices values and plasma concentrations of thiobarbituric acid reactive substances were significantly elevated in obese women (P < .001). There was a significant association between adiposity indices and selenium status (P < .001), and between erythrocyte selenium and erythrocyte glutathione peroxidase activity (P < .001). CONCLUSION: Obese women evaluated in the study have reduced plasma and erythrocyte concentrations of selenium and an increased urinary excretion of selenium. The correlation analysis reveals an association between intra-abdominal fat accumulation and selenium metabolism and oxidative stress.

Predicting Cardiometabolic Risk From Visceral Abdominal Adiposity in Persons With Chronic Spinal Cord Injury.

Persons with spinal cord injury (SCI) have increased adiposity that may predispose to cardiovascular disease compared to those who are able-bodied (AB). The purpose of this study was to determine the relationships between dual energy X-ray absorptiometry (DXA)-derived visceral adipose tissue (VAT) and biomarkers of lipid metabolism and insulin resistance in persons with chronic SCI. A prospective observational study in participants with chronic SCI and age- and gender-matched AB controls. The study was conducted at a Department of Veterans Affairs Medical Center and Private Rehabilitation Hospital. The quantification of DXA-derived VAT volume (VATvol) and blood-derived markers of lipid and carbohydrate metabolism were determined in 100 SCI and 51 AB men. The VATvol was acquired from a total body DXA scan and analyzed using iDXA enCore CoreScan software (GE Lunar). Blood samples were collected for the serum lipid profile and plasma and glucose concentrations, with the latter two values used to calculate a measure of insulin resistance. In the SCI and AB groups, VAT% was significantly correlated with most cardiometabolic biomarkers. The results of the binary logistic regression analysis revealed that participants who had a VATvol above the cutoff value of 1630 cm3 were 3.1-, 4.8-, 5.6-, 19.2-, and 16.7-times more likely to have high serum triglycerides (R2N= 0.09, p = 0.014), low serum high density lipoprotein cholesterol (R2N = 0.16, p < 0.001), HOMA2-IR (R2N = 0.18, p < 0.001), metabolic syndrome (R2N = 0.25, p < 0.001), and a 10-yr Framingham Risk Score ≥ 10% (R2N = 0.16, p = 0.001), respectively, when compared to participants below this VATvol cutoff value. Our findings reveal that persons with chronic SCI have a higher VATvol than that of AB controls, and VATvol correlates directly with biomarkers of lipid and carbohydrate metabolism that are strong predictors of cardiometabolic disorders.

Effects of waist to height ratio, waist circumference, body mass index on the risk of chronic diseases, all-cause, cardiovascular and cancer mortality.

BACKGROUND: Given the fat redistribution in later stages of life, how the associations between abdominal obesity and the risk of morbidity and mortality have changed with age have not been elucidated, especially for waist to height ratio (WHtR). OBJECTIVE: To compare the strength of association between obesity indices and chronic diseases at baseline, and the subsequent mortality risk among US adults. METHODS: We included 21 109 participants from National Health and Nutrition Examination Survey 1999-2014. We performed logistic regression and receiver operating curve analysis to examine the discriminatory power of obesity indicators on cardiometabolic diseases and cancer at baseline. Sex-stratified and age-stratified Cox models were constructed to explore the prospective association between obesity indices and all-cause, cardiovascular and cancer mortality. RESULTS: Elevated WHtR, elevated waist circumference (WC) and body mass index (BMI)-classified obesity are associated with higher odds of hypertension (OR: 1.37-2.13), dyslipidemia (OR: 1.06 to 1.75, all p<0.05) and diabetes (OR: 1.40-3.16, all p<0.05). WHtR had significantly better discriminatory power to predict cardiometabolic health than BMI, especially for diabetes (area under the curve: 0.709 vs 0.654). After multivariable adjustment, all obesity indicators are associated with lower risk of all-cause mortality among females aged ≥65 years (HR: 0.64 to 0.85), but the association was only significant for BMI when obesity indicators were mutually adjusted (HR: 0.79). CONCLUSIONS: WHtR and WC appeared to be the better indicators for cardiometabolic health than BMI. However, BMI had a stronger and inverse association with a greater risk of all-cause mortality among older females.

Role of Adipose Tissue in Inflammatory Bowel Disease.

Inflammatory bowel diseases (IBDs), chronic inflammatory disorders affecting the gastrointestinal tract, include Crohn's disease and ulcerative colitis. There are increasing clinical and experimental data showing that obesity, especially visceral adiposity, plays a substantial role in the pathogenesis of IBD. Obesity seems to be an important risk factor also for IBD disease severity and clinical outcomes. Visceral adipose tissue is an active multifunctional metabolic organ involved in lipid storage and immunological and endocrine activity. Bowel inflammation penetrates the surrounding adipose tissue along the mesentery. Mesenteric fat serves as a barrier to inflammation and controls immune responses to the translocation of gut bacteria. At the same time, mesenteric adipose tissue may be the principal source of cytokines and adipokines responsible for inflammatory processes associated with IBD. This review is particularly focusing on the potential role of adipokines in IBD pathogenesis and their possible use as promising therapeutic targets.

Pathophysiology of human visceral obesity: an update.

Excess intra-abdominal adipose tissue accumulation, often termed visceral obesity, is part of a phenotype including dysfunctional subcutaneous adipose tissue expansion and ectopic triglyceride storage closely related to clustering cardiometabolic risk factors. Hypertriglyceridemia; increased free fatty acid availability; adipose tissue release of proinflammatory cytokines; liver insulin resistance and inflammation; increased liver VLDL synthesis and secretion; reduced clearance of triglyceride-rich lipoproteins; presence of small, dense LDL particles; and reduced HDL cholesterol levels are among the many metabolic alterations closely related to this condition. Age, gender, genetics, and ethnicity are broad etiological factors contributing to variation in visceral adipose tissue accumulation. Specific mechanisms responsible for proportionally increased visceral fat storage when facing positive energy balance and weight gain may involve sex hormones, local cortisol production in abdominal adipose tissues, endocannabinoids, growth hormone, and dietary fructose. Physiological characteristics of abdominal adipose tissues such as adipocyte size and number, lipolytic responsiveness, lipid storage capacity, and inflammatory cytokine production are significant correlates and even possible determinants of the increased cardiometabolic risk associated with visceral obesity. Thiazolidinediones, estrogen replacement in postmenopausal women, and testosterone replacement in androgen-deficient men have been shown to favorably modulate body fat distribution and cardiometabolic risk to various degrees. However, some of these therapies must now be considered in the context of their serious side effects. Lifestyle interventions leading to weight loss generally induce preferential mobilization of visceral fat. In clinical practice, measuring waist circumference in addition to the body mass index could be helpful for the identification and management of a subgroup of overweight or obese patients at high cardiometabolic risk.

Association of selected adipokines with metabolic syndrome and cardio-metabolic risk factors in young males.

The study aimed to investigate association of circulating leptin, adiponectin, chemerin, and omentin-1 with metabolic syndrome (MetS) and cardio-metabolic risk factors in youths. Thirty eight young males were enrolled. Participants underwent anthropometric and blood pressure measures, and fasting blood sampling. Plasma leptin, adiponectin, chemerin, omentin-1 and insulin were measured by ELISA methods. Multiple linear regression models, adjusting for age, MetS traits, C-reactive protein (CRP) and homeostasis model assessment of insulin resistance (HOMA-IR), were applied to determine correlates for each adipokine. Eleven participants meet criteria of MetS. These individuals had higher leptin and chemerin and lower adiponectin plasma concentrations than those without MetS. Plasma leptin and chemerin were positively related, and adiponectin and omentin-1 were inversely related to cardio-metabolic traits. In multivariate models, predictors of leptin were age (ß, 0.20, P = 0.01), abdominal obesity (ß, 0.24, P = 0.06), raised blood pressure (ß, 0.40, P = 0.01), raised triglycerides (ß, 0.19, P = 0.01) and CRP (ß, 0.31, P = 0.01). Chemerin was associated with abdominal obesity (ß, 0.33, P = 0.09) and CRP (ß, 0.29, P = 0.04), and adiponectin was associated with raised triglycerides (ß, -0.26, P = 0.05), decreased HDL-C (ß, -0.28, P = 0.06) and CRP (ß, -0.48, P = 0.01). HOMA-IR (ß, -0.39, P = 0.09) was the only predictor for omentin. MetS is associated with an altered plasma adipokines profile, with increased leptin and chemerin and decreased adiponectin circulating levels. These findings suggest a beneficial potential of adiponectin and omentin, but a detrimental potential of leptin and chemerin. Further research is needed to lighten the role of adipose tissue-derived adipokines in cardio-metabolic health.