Visceral Adipose Tissue Dysfunction Research Articles

Association between Visceral Adipose Tissue Metabolism and Cerebral Glucose Metabolism in Patients with Cognitive Impairment.

Visceral adipose tissue (VAT) dysfunction has been recently recognized as a potential contributor to the development of Alzheimer's disease (AD). This study aimed to explore the relationship between VAT metabolism and cerebral glucose metabolism in patients with cognitive impairment. This cross-sectional prospective study included 54 patients who underwent 18F-fluorodeoxyglucose (18F-FDG) brain and torso positron emission tomography/computed tomography (PET/CT), and neuropsychological evaluations. VAT metabolism was measured by 18F-FDG torso PET/CT, and cerebral glucose metabolism was measured using 18F-FDG brain PET/CT. A voxel-based analysis revealed that the high-VAT-metabolism group exhibited a significantly lower cerebral glucose metabolism in AD-signature regions such as the parietal and temporal cortices. In the volume-of-interest analysis, multiple linear regression analyses with adjustment for age, sex, and white matter hyperintensity volume revealed that VAT metabolism was negatively associated with cerebral glucose metabolism in AD-signature regions. In addition, higher VAT metabolism was correlated with poorer outcomes on cognitive assessments, including the Korean Boston Naming Test, Rey Complex Figure Test immediate recall, and the Controlled Oral Word Association Test. In conclusion, our study revealed significant relationships among VAT metabolism, cerebral glucose metabolism, and cognitive function. This suggests that VAT dysfunction actively contributes to the neurodegenerative processes characteristic of AD, making VAT dysfunction targeting a novel AD therapy approach.

Adipose tissue macrophage–derived microRNA-210-3p disrupts systemic insulin sensitivity by silencing GLUT4 in obesity

Management of chronic obesity-associated metabolic disorders is a key challenge for biomedical researchers. During chronic obesity, visceral adipose tissue (VAT) undergoes substantial transformation characterized by a unique lipid-rich hypoxic AT microenvironment (ATenv) which plays a crucial role in VAT dysfunction, leading to insulin resistance (IR) and type 2 diabetes(T2D). Here, we demonstrate that obese ATenv triggers the release of miR-210-3p microRNA-loaded extracellular vesicles (EVs) from adipose tissue macrophages (ATMs), which disseminate miR-210-3p to neighboring adipocytes, skeletal muscle cells, and hepatocytes through paracrine and endocrine actions, thereby influencing insulin sensitivity. Moreover, EVs collected from Dicer-silenced miR-210-3p-overexpressed bone marrow-derived macrophages (BMDMs), induce glucose intolerance and IR in lean mice. Mechanistically, miR-210-3p interacts with the 3′-UTR of GLUT4 mRNA and silences its expression, compromising cellular glucose uptake and insulin sensitivity. Therapeutic inhibition of miR-210-3p in VAT notably rescues high-fat diet (HFD)-fed mice from obesity-induced systemic glucose intolerance. Thus, targeting ATM-specific miR-210-3p during obesity could be a promising strategy for managing IR and T2D.

Association between visceral adiposity index and coronary artery calcification score and atherosclerotic plaque morphology.

The relationship between the visceral adipose index (VAI), a surrogate marker of visceral adipose tissue dysfunction, and coronary atherosclerotic plaque (CAP) morphology remains unclear. This study aimed to investigate the relationships between the VAI and the coronary artery calcification (CAC) score and CAP morphology in asymptomatic patients. We retrospectively assessed 782 patients between January 2012 and January 2020. CAC scores were determined at the threshold of 130 Hounsfield units according to the Agatston technique using 64-slice computed tomography. Patients were assigned to groups with no plaque (NP), fatty plaque (FP), calcified plaque (CP), and mixed plaque (MP). The median VAI levels were significantly different in each group (NP: 1.2 vs. FP: 1.7 vs. CP: 2.3 vs. MP: 2.8; P <0.001). An increased VAI level was an independent predictor of the CAC score. The threshold value of the VAI exhibited a gradual increase in predicting CAP morphology. VAI threshold values were >1.6 for the FP group (vs. the NP group), >2.1 for the CP group (vs. the FP group), and >2.6 for the MP group (vs. the CP group). High VAI levels independently predict an increased CAC score and CAP morphology. The VAI exhibits superior diagnostic performance in distinguishing the presence and morphology of CAP in asymptomatic patients and offers gradual cut-off values. Therefore, the VAI may be a potential screening tool for risk stratification and diagnosing CAP morphology in patients with suspected coronary artery disease.

CX3CR1hi macrophages sustain metabolic adaptation by relieving adipose-derived stem cell senescence in visceral adipose tissue

Adipose-derived stem cells (ASCs) drive healthy visceral adipose tissue (VAT) expansion via adipocyte hyperplasia. Obesity induces ASC senescence that causes VAT dysfunction and metabolic disorders. It is challenging to restrain this process by biological intervention, as mechanisms of controlling VAT ASC senescence remain unclear. We demonstrate that a population of CX3CR1hi macrophages is maintained in mouse VAT during short-term energy surplus, which sustains ASCs by restraining their senescence, driving adaptive VAT expansion and metabolic health. Long-term overnutrition induces diminishment of CX3CR1hi macrophages in mouse VAT accompanied by ASC senescence and exhaustion, while transferring CX3CR1hi macrophages restores ASC reservoir and triggers VAT beiging to alleviate the metabolic maladaptation. Mechanistically, visceral ASCs attract macrophages via MCP-1 and shape their CX3CR1hi phenotype via exosomes; these macrophages relieve ASC senescence by promoting the arginase1-eIF5A hypusination axis. These findings identify VAT CX3CR1hi macrophages as ASC supporters and unravel their therapeutic potential for metabolic maladaptation to obesity.

Differential Expression of FXR and Genes Involved in Inflammation and lipid Metabolism Indicate Adipose Tissue Dysfunction in Gestational Diabetes

Gestational diabetes mellitus (GDM) is the most frequent metabolic alteration in pregnancy. Several abnormalities in visceral adipose tissue (VAT) have been described as part of its pathophysiology including hypertrophy, inflammation and altered lipid metabolism. Farnesoid X receptor (FXR) is involved in adipocyte physiology and inflammation, so its expression may correlate with the expression of tumor necrosis factor-alpha (TNF-α), interleukin-10 (IL-10), lipoprotein lipase (LPL), and two fatty acid transporters (SLC27A2, and SLC27A4). To compare the FXR, LPL, SLC27A2, SLC27A4, TNF-α, and IL-10 mRNA expression in VAT between women with GDM and healthy pregnant (HP) women. Secondarily, to evaluate the potential correlation between these expression levels. Cross-sectional study of 50 GDM and 50 HP women. Conventional biochemical tests were performed and relative mRNA expression in VAT was measured by RT-qPCR. Gene expression levels of FXR and IL-10 were lower, whereas those of LPL, as well as the TNF-α/IL-10 ratio, were higher in women with GDM compared to HP. Pre-pregnancy BMI was the main significant independent variable for FXR levels in VAT from women with GDM. In all women, LPL expression levels correlated positively with those of SLC27A2. Only in women with GDM, IL-10 expression levels correlated negatively with those of SLC27A2, and SLC27A4. GDM is associated with decreased expression of FXR and IL-10 and increased expression of LPL, as well as a higher TNF/IL-10 ratio in VAT. These results suggest increased lipid storage and pro-inflammatory state indicating VAT dysfunction in this metabolic disorder.

Obesity paradox and aging: Visceral Adiposity Index and all-cause mortality in older individuals: A prospective cohort study.

BackgroundThe relationship between body mass index (BMI) and mortality in older adults diminished. It is necessary to examine other factors that may accurately predict mortality in older adults. The visceral adiposity index (VAI) is an uncomplicated marker specific to the gender that incorporates anthropometric data and lipid profiles. VAI has been proposed as a marker of visceral adipose tissue dysfunction and of the related cardiometabolic risk. The aim of this study was to evaluate the link of VAI with all-cause mortality among the elderly.MethodsThe present prospective cohort study included data from 1999 to 2014 provided by the National Health and Nutrition Examination Survey (NHANES) in the United States. NHANES participants at or above the age of 65 were included. Data collection was carried out by taking face-to-face interviews, mobile-physical examinations, and lab tests. From the start of the survey to the end of December 2015, mortality-related follow-up statistics are available. The shape of the link between VAI and all-cause mortality was investigated using a restricted cubic spline model. Univariate- and multivariate-adjusted Cox proportional hazard models were estimated for VAI, and the results were presented as regression coefficients and 95% confidence intervals (CI).ResultsThe 82,091 NHANES participants represented 442.2 million non-institutionalized residents of the United States. A total of 11,173 older individuals (representing 23.3 million; aged 73.4 ± 5.8 years; 56.3% women, 82.7% non-Hispanic Whites, 6.8% non-Hispanic Blacks, and 3.3% Mexican Americans) were included in the study. During the 80-month follow-up period, 4466 fatalities were reported, including 825 deaths from cancer, 867 from heart disease, and 211 from cerebrovascular disease. The restricted cubic spline model demonstrated a robust J-shaped link between VAI and all-cause mortality, revealing a significant decrease in risk within the lower range of VAI, which attained the lowest risk close to 1.7. With VAI greater than 1.7, the risk of mortality increased with the increase of VAI (P for non-linearity = 0.025). In the multivariate-adjusted model, the risk of all-cause mortality was 0.73 (0.56-0.97) and 1.05 (1.01-1.09) in participants with VAI less than 1.7 and VAI greater than or equal to 1.7, respectively.ConclusionThis investigation is a population-based cohort study with high sample sizes and a long-term in older individuals follow-up that showed a J-shaped link between VAI levels and all-cause mortality. Understanding the independent roles of VAI in the relationship between BMI and mortality is crucial to understanding the obesity paradox phenomenon.

Association of the cytokine profile and metabolic syndrome components in young patients

The components of metabolic syndrome (MS) are independent factors of cardiometabolic risk and are associated with impaired humoral immunity. However, the literature data on the cytokine profile features in MS are ambiguous. Therefore, associations between cytokine levels and MS components were determined in a group of MS patients of both sexes, as well as indices of visceral adipose tissue function were studied. The work included 149 patients aged 18-45 years. The patients were divided into 2 groups: group 1 (n = 71) included patients without abdominal obesity and MS components (comparison group); group 2 (n = 78), patients with MS. The concentrations of glucose, glycosylated hemoglobin, insulin, total cholesterol, HDL-C, LDL-C, triglycerides, leptin, adiponectin were determined. The indexes of insulin resistance HOMA-IR, Tg/HDL and TyG, as well as marker of visceral adipose tissue dysfunction VAI were calculated. ELISA technique was used to determine the concentration of IL-1, IL-2, IL-4, IL-6, IL-8, IL-10, IFN, IFN, МСР-1 и TNF. Results: In the patients with MS, we have found increased levels of IL-6, IL-10, MCP-1, and decrease of IL-2, IL-4, IFN levels. Correlation analysis established a relationship between glucose levels and MCP-1; glycosylated hemoglobin and IL-6, TNF. Among the indices of lipid metabolism, we have revealed some associations between LDL-C and IFN; HDL-C and IL-2, IL-4, IFN. The levels of triglycerides correlated with MCP-1. A negative relationship between the presence of arterial hypertension and the IL-4 contents was established. A negative correlation of leptin levels with IL-4 and IFN concentrations was also determined. Markers of insulin resistance (Tg/HDL and TyG) were associated with MCP-1 chemokine, thus supporting chronic inflammatory process. The VAI index, which reflects the dysfunction of visceral adipose tissue, showed a correlation with MCP-1. Thus, the results of investigation suggest an involvement of the cytokine system in the disorders of visceral adipose tissue and development of the metabolic syndrome.

Estrogen supplementation deteriorates visceral adipose function in aged postmenopausal subjects via Gas5 targeting IGF2BP1.

Increased visceral fat is strongly associated with a series of metabolic complications. Postmenopausal women have an increased risk of visceral fat accumulation, metabolic disorders, and a high incidence of cardiovascular events. However, the effect of estrogen replacement therapy on visceral adipose tissue among postmenopausal women of different ages remains controversial, and the underlying mechanism remains unclear. Hence, it is important to understand when estrogen replacement therapy affects the function of visceral adipose tissue (VAT). Therefore, we collected VAT from pre- and post-menopausal females and we observed increased pro-inflammatory cytokines and insulin resistance-inducing factors, decreased insulin-sensitizing factors, and thermogenic factors in VAT of postmenopausal women. The analysis of adipocytes isolated from the VAT of females of different ages indicated that adiponectin and browning signature genes were significantly decreased with estrogen treatment in postmenopausal women, but were not altered in the young group. Estrogen supplementation in aged female mice (22m) significantly prevented visceral fat accumulation. However, it deteriorated VAT function by inducing pro-inflammatory cytokines and insulin resistance-inducing factors and decreasing insulin-sensitizing and thermogenic factors. Mechanistically, estrogen induced the expression of long non-coding RNA Gas5 via binding ERα in premenopausal women, which therefore suppressed IGF2BP1 to maintain VAT function. After menopause, with the reversal of ERα/ERβ ratio in VAT, estrogen supplementation mainly worked through ERβ, which led to low expression levels of Gas5 and eventually caused VAT dysfunction. Our study demonstrated the adverse effects of estrogen supplementation on VAT function in aged postmenopausal population and further elucidated the involved mechanism.

Metabolik sendrom, insülin direnci, diabetes mellitus ve hipertansiyonu öngörmede visseral adipozite indeksi kesme değerlerinin belirlenmesi

Introduction: The visceral adiposity index is a reliable indicator of visceral adipose tissue dysfunction. The aim of this research was to determine the cut-off points of the visceral adiposity index in predicting metabolic syndrome, insulin resistance, type 2 diabetes mellitus, and hypertension at specific age ranges and in both sexes separately.Methods: This research is both descriptive and analytical. The research was conducted with 951 participants aged 18 and over between July 2019 and July 2020. 51 participants that did not meet study criteria were excluded from the research. The research was completed with a total of 900 participants, 577 females and 373 males. A physical examination and anthropometric measurements (height, weight, waist circumference, and blood pressure) of all participants were conducted. After 12 hours of fasting, the HDL, TG, glucose, and insulin levels of participants were measured. The blood pressure of participants was measured after 15 minutes of rest. Adult treatment panel 3 criteria were used for the diagnosis of metabolic syndrome. A homeostatic model assessment was calculated. The visceral adiposity index is calculated in the entire population for the prediction of metabolic syndrome, insulin resistance, diabetes, and hypertension: women, men, age groups 18–30, 31–40, 41–50, 51–65, 66 and over.Results: Cut-off points of the visceral adiposity index in predicting metabolic syndrome were 4.53 in the total population and males, 4.28 in females, 4.76 in the 18-30 age range, 4.96 in the 31-40 age range, 4.87 in the 41-50 age range, 5.04 in the 51-65 age range, and 4.59 in the age range 66 and above. Cut-off points of the visceral adiposity index in predicting insulin resistance were 4.24 in the total population and females, 4.68 in males, 3.45 in the 18-30 age range, 4.15 in the 31-40 age range, 4.66 in the 41-50 age range, and 4.87 in the 51-65 age range. Cut-off points of the visceral adiposity index in predicting type 2 diabetes mellitus were 4.89 in the total population, 6.43 in females, 7.02 in the 31-40 age range, 7.29 in the 41-50 age range, and 5.98 in the 51-65 age range. Cut-off points of the visceral adiposity index in predicting hypertension were 4.26 in the total population, 4.07 in females, 4.64 in the 18–30 age range, and 4.43 in the 51–65 age range.Conclusions: The visceral adiposity index can be used to predict metabolic syndrome, insulin resistance, type 2 diabetes mellitus and hypertension.

Association between Visceral Adipose Tissue Metabolism and Alzheimer's Disease Pathology.

The visceral adipose tissue (VAT) has been recognized as an endocrine organ, and VAT dysfunction could be a risk factor for Alzheimer’s disease (AD). We aimed to evaluate the association of VAT metabolism with AD pathology. This cross-sectional study included 54 older subjects with cognitive impairment who underwent 2-deoxy-2-[fluorine-18]-fluoro-D-glucose (18F-FDG) torso positron emission tomography (PET) and 18F-florbetaben brain PET. 18F-FDG uptake in VAT on 18F-FDG PET images was used as a marker of VAT metabolism, and subjects were classified into high and low VAT metabolism groups. A voxel-based analysis revealed that the high VAT metabolism group exhibited a significantly higher cerebral amyloid-β (Aβ) burden than the low VAT metabolism group. In the volume-of-interest analysis, multiple linear regression analyses with adjustment for age, sex, and white matter hyperintensity volume revealed that 18F-FDG uptake in VAT was significantly associated with the cerebral Aβ burden (β = 0.359, p = 0.007). In conclusion, VAT metabolism was associated with AD pathology in older subjects. Our findings suggest that VAT dysfunction could contribute to AD development.

Evaluation of the relationship between insulin resistance and visceral adiposity index in patients with acne vulgaris.

Acne vulgaris (AV) is a chronic inflammatory skin disease that is common among adolescents. Its etiology involves hormones, diet, genetics, and environmental factors. The aim of this study was to investigate the association between acne vulgaris and insulin resistance (IR) and visceral adiposity index (VAI). The study included 184 individuals. Participants' height, weight, waist and hip circumference and blood pressure were measured. Morning fasting blood was obtained from all participants for measuring glucose, insulin, triglyceride (TG), and cholesterol levels. The HOMA index and visceral adiposity index were calculated. The collected data were analyzed using statistical methods. The patient and control groups exhibited similar age, gender, and body mass index (p > 0.05). There was no significant difference between the patient and control groups in HOMA index and VAI (p > 0.05). A positive correlation was observed between VAI and glucose, insulin, HOMA index, TG level, and waist circumference, whereas there was a negative correlation with high-density lipoprotein (HDL). Our study results demonstrated that IR and VAI were similar both in the AV and healthy control groups. There was no correlation between acne severity score and waist circumference, glucose, insulin, TG, HDL, HOMA index, and VAI. These results indicate that IR and visceral adipose tissue dysfunction alone are not effective in the development of acne.

Features of the immune system cells in abdominal obesity and metabolic syndrome and their associations with factors of cardiometabolic risk, visceral adipose tissue dysfunction and adipokines

The aim of this work was to establish the features of the immune system cells in abdominal obesity (AO) and metabolic syndrome (MS) and to determine the associations between the studied parameters and MS components, insulin resistance, and the level of adipokines. 244 patients of both sexes aged 18–45 years were included. The patients were divided into 4 groups: group 1 (comparison group) — healthy individuals without AO, excess body weight and additional MS components (n=71); group 2 (AO) — patients with isolated AO (n=32); group 3 (AO+1) — patients with AO and 1 component of MS (n=63); group 4 (MS) — patients with MS (n=78). The laboratory investigation included determination of parameters of carbohydrate, lipid metabolism, adipokines. The calculation of insulin resistance indices and the index of dysfunction of visceral adipose tissue were performed. The parameters of cell immunity were studied (the number of leukocytes and leukocyte formula; the subpopulations of lymphocytes — CD3+45+, CD3+4+, CD3+8+, CD3+56+, CD3-56+, CD3-19+, CD3+25+ and CD3+HLADR+ ). The results of this work demonstrate inflammatory changes in the leukocyte formula, as well as the appearance of activated lymphocytes in peripheral blood in patients of groups 2–4. Correlation analysis results suggest that the mechanism of formation of changes in cell adaptive immunity in AO and MS is associated with cardiometabolic risk factors. Conclusions. 1. Changes in the leukocytes composition in peripheral blood in patients with AO and MS are an increase in the number of neutrophils, monocytes and a decrease in the number of lymphocytes. In the groups AO+1 and MS these changes are accompanied by an increase in the number of leukocytes. 2. The subpopulations of peripheral blood lymphocytes in the groups AO and AO+1 are characterized by an increase in the level of CD3+HLADR+. In patients with MS — in combination with an increase in the level of CD3+25+ and B-lymphocytes. 3. The appearance of activated lymphocytes in the peripheral blood in the groups AO and MS is associated with cardiometabolic risk factors (excess adipose tissue, dyslipidemia, hyperleptinemia, hyperinsulinemia, and insulin resistance).

Influence of endotoxemy on development of non-alcoholic fatty liver disease

Objective — to investigate endotoxin levels and to assess the relationship between endotoxemia and metabolic parameters and the degree of steatosis and fibrosis in patients with non‑alcoholic fatty liver disease (NAFLD) against the background of metabolic syndrome (MS).&#x0D; Materials and methods. The study included 68 patients with NAFLD with metabolic disorders and 20 people of the control group. Women prevailed in both investigational groups, the mean age was 49.34 ± 10.8 years. All patients underwent evaluation of their anthropometric parameters, investigation of body composition with determination of the percentage of visceral adipose tissue (VAT). To reveal VAT dysfunction, visceral adiposity index (VAI) was calculated with M. C. Amato method. Steatometry was performed by determining the wave attenuation coefficient and carrying out shear wave elastography. Endotoxin levels in blood serum were determined using a set of reagents «LAL Chromogenic Endpoint Assay» manufactured by «Hycult Biotech» (Netherlands).&#x0D; Results. Bacterial endotoxin levels in peripheral blood in the examined patients were almost three times higher in comparison with the control group (p &lt; 0.05). Patients with overweight and obesity had significantly higher endotoxin levels compared with the control group (p &lt; 0.05). The significant increase in endotoxin levels has been defined in obese NAFLD patients compared to the NAFLD patients with normal weight (p &lt; 0.05). The direct correlation was found between endotoxin parameters and parameters of abdominal and visceral obesity. In the group of patients with high VAT activity, the maximal values of this indicator were observed, which significantly differed from the corresponding indicator in patients with low and medium VAI (p &lt; 0.05). There was a direct correlation between moderate endotoxin and insulin resistance, a direct weak relationship between endotoxin and lipid profile parameters. In patients with grade 2 and 3 steatosis, significant differences in the level of endotoxemia were observed compared with the control group (p &lt; 0.05) and patients with grade 1 steatosis (p &lt; 0.05). At high grades of liver fibrosis (F3F4) there was a tendency to reduce endotoxemia compared with the low‑grade fibrosis (p &lt; 0.05).&#x0D; Conclusions. The revealed relationships between endotoxemia level and metabolic factors of NAFLD development indicate the pathogenetic role of bacterial endotoxemia in triggering a cascade of metabolic reactions with the subsequent accumulation of lipids in the liver tissue and the progression of steatosis and fibrosis.&#x0D;

Genome Profiling of H3k4me3 Histone Modification in Human Adipose Tissue during Obesity and Insulin Resistance

Background: Adipose tissue (AT) dysfunction is involved in obesity-related comorbidities. Epigenetic alterations have been recently associated with AT deterioration in obesity conditions. In this work, we profiled the H3K4me3 histone mark in human AT, with special emphasis on the changes in the pattern of histone modification in obesity and insulin resistance (IR). Visceral AT (VAT) was collected and subjected to chromatin immunoprecipitation (ChIP) using anti-H3K4me3 antibody and then sequenced to obtain the H3K4me3 genome profile. Results: We found that most of the H3K4me3 enriched regions were located in gene promoters of pathways related to AT biology and function. H3K4me3 enrichment at gene promoters was strongly related to higher mRNA levels. Differentially expressed genes in AT of patients classified as non-obese, obese with low IR, and obese with high IR could be regulated by differentially enriched H3K4me3; these genes encoded for pathways that could in part explain AT functioning during obesity and insulin resistance (e.g., extracellular matrix organization, PPARG signaling or inflammation). Conclusions: In conclusion, we emphasize the importance of the epigenetic mark H3K4me3 in VAT dysfunction in obesity and IR. The understanding of such mechanisms could give rise to the development of new epigenetic-based pharmacological strategies to ameliorate obesity-related comorbidities.

The human type 2 diabetes-specific visceral adipose tissue proteome and transcriptome in obesity

Dysfunctional visceral adipose tissue (VAT) in obesity is associated with type 2 diabetes (DM) but underlying mechanisms remain unclear. Our objective in this discovery analysis was to identify genes and proteins regulated by DM to elucidate aberrant cellular metabolic and signaling mediators. We performed label-free proteomics and RNA-sequencing analysis of VAT from female bariatric surgery subjects with DM and without DM (NDM). We quantified 1965 protein groups, 23 proteins, and 372 genes that were differently abundant in DM vs. NDM VAT. Proteins downregulated in DM were related to fatty acid synthesis and mitochondrial function (fatty acid synthase, FASN; dihydrolipoyl dehydrogenase, mitochondrial, E3 component, DLD; succinate dehydrogenase-α, SDHA) while proteins upregulated in DM were associated with innate immunity and transcriptional regulation (vitronectin, VTN; endothelial protein C receptor, EPCR; signal transducer and activator of transcription 5B, STAT5B). Transcriptome indicated defects in innate inflammation, lipid metabolism, and extracellular matrix (ECM) function, and components of complement classical and alternative cascades. The VAT proteome and transcriptome shared 13 biological processes impacted by DM, related to complement activation, cell proliferation and migration, ECM organization, lipid metabolism, and gluconeogenesis. Our data revealed a marked effect of DM in downregulating FASN. We also demonstrate enrichment of complement factor B (CFB), coagulation factor XIII A chain (F13A1), thrombospondin 1 (THBS1), and integrins at mRNA and protein levels, albeit with lower q-values and lack of Western blot or PCR confirmation. Our findings suggest putative mechanisms of VAT dysfunction in DM.

Chronic Intermittent Hypoxia Induces Early-Stage Metabolic Dysfunction Independently of Adipose Tissue Deregulation.

Several studies demonstrated a link between obstructive sleep apnea (OSA) and the development of insulin resistance. However, the main event triggering insulin resistance in OSA remains to be clarified. Herein, we investigated the effect of mild and severe chronic intermittent hypoxia (CIH) on whole-body metabolic deregulation and visceral adipose tissue dysfunction. Moreover, we studied the contribution of obesity to CIH-induced dysmetabolic states. Experiments were performed in male Wistar rats submitted to a control and high-fat (HF) diet. Two CIH protocols were tested: A mild CIH paradigm (5/6 hypoxic (5% O2) cycles/h, 10.5 h/day) during 35 days and a severe CIH paradigm (30 hypoxic (5% O2) cycles, 8 h/day) during 15 days. Fasting glycemia, insulinemia, insulin sensitivity, weight, and fat mass were assessed. Adipose tissue hypoxia, inflammation, angiogenesis, oxidative stress, and metabolism were investigated. Mild and severe CIH increased insulin levels and induced whole-body insulin resistance in control animals, effects not associated with weight gain. In control animals, CIH did not modify adipocytes perimeter as well as adipose tissue hypoxia, angiogenesis, inflammation or oxidative stress. In HF animals, severe CIH attenuated the increase in adipocytes perimeter, adipose tissue hypoxia, angiogenesis, and dysmetabolism. In conclusion, adipose tissue dysfunction is not the main trigger for initial dysmetabolism in CIH. CIH in an early stage might have a protective role against the deleterious effects of HF diet on adipose tissue metabolism.

Visceral Adiposity in Relation to Body Adiposity and Nutritional Status in Elderly Patients with Stable Coronary Artery Disease.

Introduction: The accumulation of visceral abdominal tissue (VAT) seems to be a hallmark feature of abdominal obesity and substantially contributes to metabolic abnormalities. There are numerous factors that make the body-mass index (BMI) a suboptimal measure of adiposity. The visceral adiposity index (VAI) may be considered a simple surrogate marker of visceral adipose tissue dysfunction. However, the evidence comparing general to visceral adiposity in CAD is scarce. Therefore, we have set out to investigate visceral adiposity in relation to general adiposity in patients with stable CAD. Material and methods: A total of 204 patients with stable CAD hospitalized in the Department of Medicine and the Department of Geriatrics entered the study. Based on the VAI-defined adipose tissue dysfunction (ATD) types, the study population (N = 204) was divided into four groups: (1) no ATD (N = 66), (2) mild ATD (N = 50), (3) moderate ATD (N = 48), and (4) severe ATD (N = 40). Nutritional status was assessed using the Controlling Nutritional Status (CONUT) score. Results: Patients with moderate and severe ATD were the youngest (median 67 years), yet their metabolic age was the oldest (median 80 and 84 years, respectively). CONUT scores were similar across all four study groups. The VAI had only a modest positive correlation with BMI (r = 0.59 p < 0.01) and body adiposity index (BAI) (r = 0.40 p < 0.01). There was no correlation between VAI and CONUT scores. There was high variability in the distribution of BMI-defined weight categories across all four types of ATD. A total of 75% of patients with normal nutritional status had some form of ATD, and one-third of patients with moderate or severe malnutrition did not have any ATD (p = 0.008). In contrast, 55–60% of patients with mild, moderate, or severe ATD had normal nutritional status (p = 0.008). ROC analysis demonstrated that BMI and BAI have poor predictive value in determining no ATD. Both BMI (AUC 0.78 p < 0.0001) and BAI (AUC 0.66 p = 0.003) had strong predictive value for determining severe ATD (the difference between AUC 0.12 being p = 0.0002). However, BMI predicted mild ATD and severe ATD better than BAI. Conclusions: ATD and malnutrition were common in patients with CAD. Notably, this study has shown a high rate of misclassification of visceral ATD via BMI and BAI. In addition, we demonstrated that the majority of patients with normal nutritional status had some form of ATD and as much as one-third of patients with moderate or severe malnutrition did not have any ATD. These findings have important clinical ramifications for everyday practice regarding the line between health and disease in the context of malnutrition in terms of body composition and visceral ATD, which are significant for developing an accurate definition of the standards for the intensity of clinical interventions.

The relationship between intestinal microbiota and systemic inflammation in patients with non-alcoholic fatty liver disease

Objective — to determine the relation of the main phylotypes of the intestinal microbiota (IM) with markers of systemic inflammation and the degree of hepatic steatosis in patients with non‑alcoholic fatty liver disease (NAFLD) with metabolic disorders.&#x0D; Materials and methods. The study included 114 patients with NAFLD with excessive body mass and obesity and 30 people as a control group, who were investigated on the basis of the Department of Gastroenterology and Therapy of the Polyclinics of the L. T. Mala National Therapy Institute of NAMS of Ukraine. The mean age of the investigated subjects was (52.56 ± 11.70) years. Anthropometric measurements were carried out with the calculation of the body mass index (BMI), determination of the percentage of visceral adipose tissue (VAT) using the OMRON BF‑511 body composition monitor. To determine the VAT dysfunction, the visceral obesity index (VOI) was calculated by the M. C. Amato method. Determination of CRP and TNF‑alpha levels was carried out by enzyme immunoassay. The assessment of the degree of steatosis was carried out by determining the wave attenuation coefficient (WAC) and shear wave elastometry. Determination of the composition of the intestinal microbiota at the level of the main phylotypes was carried out by identifying the total bacterial DNA and DNA of Bacteroidetes, Firmicutes, and Actinobacteria by the method of quantitative polymerase chain reaction (PCR) in real time.&#x0D; Results. The NAFLD patients displayed significantly increased levels of CRP and TNF‑alpha in comparison with the control group. A weak direct correlation has been established between CRP, TNF‑alpha and Firmicutes (r = 0.24 (p = 0.0029) and r = 0.17 (p = 0.0350), respectively), and an inverse correlation dependence of CRP on Bacteroidetes (r` = – 0.29 (p = 0.0003)). Analysis of the dependence of the ratio of the main intestinal phyla (Firmicutes/Bacteroidetes) on markers of systemic inflammation in NAFLD patients with different activity of visceral adipose tissue (VAT) revealed an increase in the ratio of the main phyla of IM with an increase in VAT activity. In the group of NAFLD patients with high VAT activity maximum values of the Firmicutes/Bacteroidetes ratio have been defined. Patients with increased levels of CRP an TNF‑alpha displayed an increase in the Firmicutes/Bacteroidetes ratio. Patients with advanced steatosis showed more significant changes in the main phyla of IM towards an increase in Firmicutes.&#x0D; Conclusions. The dependence of the Firmicutes/Bacteroidetes ratio from the markers of systemic inflammation and VAT activity has been established. The maximum values of the index (Firmicutes/Bacteroidetes) were observed in NAFLD patients with a high degree of visceral obesity index and hepatic steatosis as well as elevated CRP and TNF‑alpha levels.&#x0D;

Countering adipose tissue dysfunction could underlie the superiority of telmisartan in the treatment of obesity-related hypertension

BackgroundThe prevalence of hypertension and obesity has increased significantly in recent decades. Hypertension and obesity often coexist, and both are associated with increased cardiovascular mortality. Obese hypertensive patients usually require special anti-hypertensive treatment strategy due to the increased risk of treatment resistance. Molecules that can target both obesity and hypertension underlying pathologies should get more attention. Herein, we evaluated the therapeutic effects of telmisartan, with special interest in visceral adipose tissue dysfunction, in obesity-related hypertension rat model.MethodsThirty male Wistar rats weighing 150–200 g were equally divided into: 1—Control group (fed normal laboratory diet for 24 weeks), 2—Diet-induced obesity group (DIO, fed high fat diet for 24 weeks), and 3—Diet-induced obesity treated with telmisartan group (DIO + Tel, fed high fat diet and received telmisartan for 24 weeks). At the end of the study, anthropometrical parameters were evaluated. Systolic blood pressure and heart rate were measured. Blood samples were collected for the measurement of serum lipids, adipokines, cardiac, renal, inflammatory, and oxidative stress biomarkers. Kidneys were removed and used for histopathological studies, and visceral adipose tissue was utilized for histopathological, immunohistochemical and RT-PCR studies.ResultsHigh fat diet resulted in obesity-related changes in anthropometrical parameters, elevation of blood pressure, increase in heart rate, higher serum levels of cardiac, inflammatory and kidney function biomarkers, with altered serum lipids, adipokines and oxidative stress markers. Morphological changes (H&E and PAS-stained sections) were noticed in kidneys and visceral adipose tissue. Immunohistochemistry and RT-PCR studies confirmed adipose tissue dysfunction and over-expression of inflammatory and oxidative stress proteins. Telmisartan countered obesity-induced alterations in cardiovascular, renal, and adipose tissue functions.ConclusionAdipose tissue dysfunction could be the core pathophysiology of obesity-related hypertension. Besides its anti-hypertensive effect, telmisartan had profound actions on visceral adipose tissue structure and function. Attention should be given to polymodal molecules targeting adipose tissue-related disorders.

Reduced Biliverdin Reductase-A Expression in Visceral Adipose Tissue is Associated with Adipocyte Dysfunction and NAFLD in Human Obesity

Biliverdin reductase A (BVR-A) is an enzyme involved in the regulation of insulin signalling. Knockout (KO) mice for hepatic BVR-A, on a high-fat diet, develop more severe glucose impairment and hepato-steatosis than the wild type, whereas loss of adipocyte BVR-A is associated with increased visceral adipose tissue (VAT) inflammation and adipocyte size. However, BVR-A expression in human VAT has not been investigated. We evaluated BVR-A mRNA expression levels by real-time PCR in the intra-operative omental biopsy of 38 obese subjects and investigated the association with metabolic impairment, VAT dysfunction, and biopsy-proven non-alcoholic fatty liver disease (NAFLD). Individuals with lower VAT BVR-A mRNA levels had significantly greater VAT IL-8 and Caspase 3 expression than those with higher BVR-A. Lower VAT BVR-A mRNA levels were associated with an increased adipocytes’ size. An association between lower VAT BVR-A expression and higher plasma gamma-glutamyl transpeptidase was also observed. Reduced VAT BVR-A was associated with NAFLD with an odds ratio of 1.38 (95% confidence interval: 1.02–1.9; χ2 test) and with AUROC = 0.89 (p = 0.002, 95% CI = 0.76–1.0). In conclusion, reduced BVR-A expression in omental adipose tissue is associated with VAT dysfunction and NAFLD, suggesting a possible involvement of BVR-A in the regulation of VAT homeostasis in presence of obesity.