Heterogeneity of abdominal obesity in patients with cardiovascular diseases

Aim: To assess the content of visceral adipose tissue (VAT) in patients with abdominal obesity and its relationship with metabolic disorders.Material and methods. Patients with abdominal obesity (n=107) were included in the study. All participants had an assessment of anthropometric parameters (height, weight), calculation of body mass index (BMI), proportion of total adipose tissue and VAT (bioimpedance analyzer), high-density lipoprotein cholesterol (HDL-c) levels, triglycerides, fasting blood glucose, epicardial thickness adipose tissue (two-dimensional echocardiography).Results. The median share of VAT (bioimpedance method) was 13%. Patients with abdominal obesity are divided by VAT into 2 groups: ≥14% or ≤13%. Patients with VAT≥14% had significantly higher levels of triglycerides (1.76 [1.27; 2.38] mmol / L) and glucose (6.33 [5.78; 7.87] mmol / L), and below HDL-c levels (0.95 [0.85; 1.21] mmol / L) compared with patients with VAT≤13% (1.32 [1.02; 1.50], 5.59 [5, 11; 6.16] and 1.31 [1.07; 1.58] mmol / L, respectively; p<0.001 for all three comparisons). A significant correlation was found between VAT and triglyceride, glucose and HDL-c levels (r=0.40; r=0.40; r=-0.31, respectively; p<0.001).Conclusion. Persons with abdominal obesity are heterogeneous in the proportion of VAT. The proportion of VAT above the median is associated with metabolic disorders that are significant for the development and progression of atherosclerosis. An increase in BMI in obese individuals is not associated with an increase in VAT and an increase in the severity of metabolic disorders.

Integrative Lipidomics and Metabolomics for System-Level Understanding of the Metabolic Syndrome in Long-Term Treated HIV-Infected Individuals

People living with HIV (PLWH) require life-long anti-retroviral treatment and often present with comorbidities such as metabolic syndrome (MetS). Systematic lipidomic characterization and its association with the metabolism are currently missing. We included 100 PLWH with MetS and 100 without MetS from the Copenhagen Comorbidity in HIV Infection (COCOMO) cohort to examine whether and how lipidome profiles are associated with MetS in PLWH. We combined several standard biostatistical, machine learning, and network analysis techniques to investigate the lipidome systematically and comprehensively and its association with clinical parameters. Additionally, we generated weighted lipid-metabolite networks to understand the relationship between lipidomic profiles with those metabolites associated with MetS in PLWH. The lipidomic dataset consisted of 917 lipid species including 602 glycerolipids, 228 glycerophospholipids, 61 sphingolipids, and 26 steroids. With a consensus approach using four different statistical and machine learning methods, we observed 13 differentially abundant lipids between PLWH without MetS and PLWH with MetS, which mainly belongs to diacylglyceride (DAG, n = 2) and triacylglyceride (TAG, n = 11). The comprehensive network integration of the lipidomics and metabolomics data suggested interactions between specific glycerolipids’ structural composition patterns and key metabolites involved in glutamate metabolism. Further integration of the clinical data with metabolomics and lipidomics resulted in the association of visceral adipose tissue (VAT) and exposure to earlier generations of antiretroviral therapy (ART). Our integrative omics data indicated disruption of glutamate and fatty acid metabolism, suggesting their involvement in the pathogenesis of PLWH with MetS. Alterations in the lipid homeostasis and glutaminolysis need clinical interventions to prevent accelerated aging in PLWH with MetS.

Association between visceral adipose tissue volume, measured using computed tomography, and cardio-metabolic risk factors

We evaluated the associations between metabolic parameters with visceral adipose tissue (VAT) volume in women with prediabetes or type 2 diabetes (T2DM), and we compared the VAT volume with the VAT area. We enrolled women aged > 20 years with prediabetes or T2DM, who underwent oral glucose tolerance test and whose VAT was evaluated using computed tomography (CT) at our institution between 2017 and 2019. All participants underwent unenhanced spiral CT with a 3-mm slice thickness from the level of the diaphragm to the level of the mid-thigh. The two VAT areas were defined as the free drawn area on the levels of the umbilicus and L2 vertebra. The VAT areas were also manually drawn from the level of the diaphragm to the level of the pelvic floor and were used to calculate the VAT volumes by summing all areas with a slice thickness of 3 mm after setting the attenuation values from −45 to −195 Hounsfield Unit. All metabolic characteristics, except blood pressure, were significantly correlated with the VAT volume. The VAT areas measured at the level of the L2 vertebra and umbilicus were correlated with serum triglyceride, high-density lipoprotein cholesterol, and Framingham steatosis index alone. Multivariable regression analyses revealed that the VAT volume was significantly associated with several metabolic parameters. In conclusion, in women with prediabetes and T2DM, the VAT volume acquired from CT-based calculation has more significant correlations with metabolic risk factors compared with the VAT area.

The crosstalk between gut microbiota, intestinal immunological niche and visceral adipose tissue as a new model for the pathogenesis of metabolic and inflammatory diseases: the paradigm of type 2 diabetes mellitus

Gut microbiota (GM) comprises more than one thousand microorganisms between bacterial species, viruses, fungi, and protozoa, and represents the main actor of a wide net of molecular interactions, involving, among others, the endocrine system, immune responses, and metabolism. GM influences many endocrine functions such as adrenal steroidogenesis, thyroid function, sexual hormones, IGF-1 pathway and peptides produced in gastrointestinal system. It is fundamental in glycaemic control and obesity, while also exerting an important function in modulating the immune system and associated inflammatory disease. The result of this crosstalk in gut mucosa is the formation of the intestinal immunological niche. Visceral adipose tissue (VAT) produces about 600 different peptides, it is involved in lipid and glucose metabolism and in some immune reactions through several adipokines. GM and VAT interact in a bidirectional fashion: while gut dysbiosis can modify VAT adipokines and hormone secretion, VAT hyperplasia modifies GM composition. Acquired or genetic factors leading to gut dysbiosis or increasing VAT (i.e., Western diet) induce a proinflammatory condition, which plays a pivotal role in the development of dysmetabolic and immunologic conditions, such as diabetes mellitus. Diabetes is clearly associated with specific patterns of GM alterations, with an abundance or reduction of GM species involved in controlling mucosal barrier status, glycaemic levels and exerting a pro- or anti-inflammatory activity. All these factors could explain the higher incidence of several inflammatory conditions in Western countries; furthermore, besides the specific alterations observed in diabetes, this paradigm could represent a common pathway acting in many metabolic conditions and could pave the way to a new, interesting therapeutic approach.

Electroacupuncture Stimulation Regulates Adipose Lipolysis via Catecholamine Signaling Mediated by NLRP3 Suppression in Obese Rats

Chronic low-grade inflammation of visceral adipose tissue can cause obesity-associated insulin resistance, leading to metabolic syndrome. However, anti-inflammatory drugs and those for obesity management can lead to serious side effects such as abnormal heart rate and blood pressure. Consequently, this study aimed to explore the therapeutic potential of electroacupuncture stimulation (ES) for obesity and associated chronic inflammation. Sprague-Dawley male rats were fed a high-fat diet (HFD) for ten weeks to build an obesity model, and half of the diet-induced obesity (DIO) rats were received ES. The levels of inflammatory factors were detected by ELISA and qPCR analysis. The nerve-associated macrophages were marked with immunofluorescence staining. The molecular mechanism of NLRP3 inflammasome in ES was determined by the NLRP3 inflammasome activation model. Compared to HDF rats, ES showed decreased body weight and chronic inflammatory damage. Specifically, this occurred via a decrease in monoamine oxidase-A (MAOA) expression, which suppressed noradrenaline degradation. MAOA is expressed in nerve-associated macrophages (NAMs), and ES attenuated NAMs by suppressing the NLRP3 inflammasome. The NLRP3 agonist blocked the noradrenaline degradation-reducing effect of ES, and an increase in lipolysis via the inhibition of the NLRP3 inflammasome attenuated NAMs. Thus, our findings suggest that ES induced lipolysis via activation of the NLRP3 inflammasome in nerve-associated macrophages (NAMs), independently of sympathetic nervous system activity.

Pre-Clinical Evidence for the Anti-Obesity Potential of Quercetin and Curcumin Loaded Chitosan/PEG Blended PLGA Nanoparticles

This research aimed to formulate quercetin (Qu) and curcumin (CUR)-loaded PLGA NPs coated with chitosan (CS) & PEG and to explore their therapeutic effect against obesity in rats. Qu and CUR nanostructures were prepared and characterized by Zetasizer and TEM. Then, the formulated nanoparticles and their free couterparts were employed for mitigation of obesity in female rats. The size of NPs was in nanometer range with an average size distribution 307.9 nm for Qu NPs and 322.5 nm for CUR NPs. The Qu NPs and CUR NPs were appeared in the TEM image containing core in which the Qu or CUR was localized and surrounded by the coat of PLGA-CS-PEG. The Qu NPs exhibited negative zeta potential at -8.5 mV, while, CUR NPs exhibited positive zeta potential at +0.916 mV. Treatment with orlistat, free Qu, Qu NPs, free CURor CUR NPs elicited significant decline in body weight, BMI and Lee index. Orlistat and CUR NPs significantly diminished liver, heart and visceral adipose tissue weights. Furthermore, the suggested treatments significantly reduced the gonadal and subcutaneous adipose tissue weights. Orlistat significantly lessened kidney and adrenal weights. All treatments significantly minimized serum Chol., TG, LDL, glucose, INS, HOMA-IR, LH, MDA, TLR4 and NF-κB levels and elevated serum HDL, E2 and TAC levels. Orlistat significantly enhanced serum IL-10 level. Conclusively, Qu and CUR nanoformulations offer anti-obesity potency through their hypolipidemic, hypoglycemic,antioxidative and anti-inflammatory effects. Both Qu and CUR NPs manifested superior effect than their free counterparts, may be because of solubility elevation as well as bioavailability of the nanoencapsulation.

Multidisciplinary Residential Program for the Treatment of Obesity: How Body Composition Assessed by DXA and Blood Chemistry Parameters Change During Hospitalization and Which Variations in Body Composition Occur from Discharge Up to One Year Follow-Up

Purpose Since obesity is a pathology characterized by a complex variable clinical presentation with comorbidities, multidisciplinary residential program (MRP) represents one of the best options for treating obesity. The purpose of this study was to evaluate the effectiveness of 8-weeks MRP on weight loss, body composition assessed by DXA and metabolic blood parameters between entry (T0) and discharge (T1). The secondary endpoint was the evaluation of the patients' adherence to diet during the check-up outpatient visits, at 2 (T2), 6 (T3) and 12 (T4) months after discharge. Methods One hundred and seventy-eight subjects were enrolled (61 males and 117 females, aged 58.5±13, BMI 41.3±6). The difference in values ​​(end of hospitalization compared to baseline) was calculated through the univariate GLM procedure, which provides regression analysis and analysis of variance for a variable dependent on one or more variables. Results There was a statistically significant (p<0.001) improvement of all parameters investigated: total mass (-5.68 kg), fat free mass (-1236.03 g), fat mass (-4416.85 g), fat mass index (-1724.56), visceral adipose tissue (-332.76 g), arm circumference (-1.63 cm) and calf circumference (-1.16 cm). The skeletal muscle index was not affected. Statistically significant improvement in glycaemic and lipid profile were reported. The BMI average reduction continued from discharge until T4. No statistically significant changes in fat free mass and visceral adipose tissue (VAT) were reported during a year of follow-up. Conclusion The present study demonstrated the clinical benefits of 8-weeks MRP, which includes hypocaloric diet, physical exercise, and psychological support.

CD147 Levels in Blood and Adipose Tissues Correlate with Vascular Dysfunction in Obese Diabetic Adults

CD147 is a glycoprotein that stimulates the production of matrix metalloproteinases (MMPs), known contributors to cardiovascular risk. The activity of CD147 protein depends on its glycosylation. However, it is unclear whether CD147 protein expression or glycosylation are influenced by the diabetic milieu characterized by hyperglycemia and abundant glycation-end-products (AGEs). We examined the circulating and visceral adipose tissue (VAT) levels of CD147 and their correlation with vascular function in obese, obese diabetic, and non-obese controls (n = 40, each). The circulating levels of CD147 and the glycosylated CD147 protein in VAT were considerably higher in obese, particularly obese diabetic subjects compared to controls. Obese diabetics had the lowest brachial and arteriolar vasoreactivity and the highest carotid pulse-wave velocity (PWV, a measure of arterial stiffness) among the three groups. CD147 correlated positively with body mass index (BMI), total and visceral fat mass, PWV, and plasma levels of glucose, insulin, MMPs, and AGEs and negatively with brachial artery and VAT-arteriolar vasoreactivity and nitric oxide production. Multivariate regression revealed that BMI, body fat mass, insulin, and glucose levels significantly predicted CD147. Our data suggest that higher levels of CD147 in obese subjects, particularly those with diabetes, are linked to vascular dysfunction and several cardiometabolic risk factors.