Proinflammatory cytokines are critically involved in the alteration of adipose tissue biology leading to deterioration of glucose homeostasis in obesity. Here we show a pronounced proinflammatory signature of adipose tissue macrophages in type 2 diabetic obese patients, mainly driven by increased NLRP3-dependent interleukin (IL)-1β production. IL-1β release increased with glycemic deterioration and decreased after gastric bypass surgery.
View Article and Find Full Text PDFContext: Liver and white adipose tissue (WAT) develop inflammation and fibrosis.
Objective: The aim of the study was to evaluate the bioclinical relevance of WAT fibrosis in morbid obesity and diabetes and the relationships with tissue stiffness measured using a novel device.
Design And Setting: Observational and longitudinal studies were conducted in a hospital nutrition department.
Background: Nocturnal hypoxia, the hallmark of OSA, is a potential contributing factor for nonalcoholic fatty liver disease (NAFLD). NAFLD severity and its implication in OSA-related endothelial dysfunction have not been investigated in a large, unselected OSA population, including nonobese subjects.
Methods: Noninvasive blood tests (SteatoTest, NashTest, and FibroTest) were used to evaluate steatosis, nonalcoholic steatohepatitis (NASH), and fibrosis in a large cohort of patients with OSA.
Background: The ability to identify obese subjects who will lose weight in response to energy restriction is an important strategy in obesity treatment.
Objective: We aimed to identify obese subjects who would lose weight and maintain weight loss through 6 wk of energy restriction and 6 wk of weight maintenance.
Design: Fifty obese or overweight subjects underwent a 6-wk energy-restricted, high-protein diet followed by another 6 wk of weight maintenance.
Trends Endocrinol Metab
December 2013
Chronic inflammation of adipose tissue is viewed as a hallmark of obesity and contributes to the development of type 2 diabetes and cardiovascular disease. According to current models, nutrient excess causes metabolic and structural changes in adipocytes, which initiate transcriptional programs leading to the expression of inflammatory molecules and the subsequent recruitment of immune cells. Recent advances in deciphering the underlying mechanisms revealed that key regulatory events occur at the genomic and epigenomic levels.
View Article and Find Full Text PDFDuring obesity, chronic inflammation of human white adipose tissue (WAT) is associated with metabolic and vascular alterations. Endothelial cells from visceral WAT (VAT-ECs) exhibit a proinflammatory and senescent phenotype and could alter adipocyte functions. We aimed to determine the contribution of VAT-ECs to adipocyte dysfunction related to inflammation and to rescue these alterations by anti-inflammatory strategies.
View Article and Find Full Text PDFObjective: Obesity is associated with cardiovascular risk and a low-grade inflammatory state in both blood and adipose tissue (AT). Whether inflammation contributes to vascular alteration remains an open question. To test this hypothesis, we measured arterial intima-media thickness (IMT), which reflects subclinical atherosclerosis, in severely obese subjects and explored associations with systemic inflammation and AT inflammation.
View Article and Find Full Text PDFComplex gene-environment interactions are considered important in the development of obesity. The composition of the gut microbiota can determine the efficacy of energy harvest from food and changes in dietary composition have been associated with changes in the composition of gut microbial populations. The capacity to explore microbiota composition was markedly improved by the development of metagenomic approaches, which have already allowed production of the first human gut microbial gene catalogue and stratifying individuals by their gut genomic profile into different enterotypes, but the analyses were carried out mainly in non-intervention settings.
View Article and Find Full Text PDFWe are facing a global metabolic health crisis provoked by an obesity epidemic. Here we report the human gut microbial composition in a population sample of 123 non-obese and 169 obese Danish individuals. We find two groups of individuals that differ by the number of gut microbial genes and thus gut bacterial richness.
View Article and Find Full Text PDFFibrosis is increasingly appreciated as a major player in adipose tissue dysfunction. In rapidly expanding adipose tissue, pervasive hypoxia leads to an induction of HIF1α that in turn leads to a potent profibrotic transcriptional program. The pathophysiological impact of adipose tissue fibrosis is likely to play an equally important role on systemic metabolic alterations as fibrotic conditions play in the liver, heart, and kidney.
View Article and Find Full Text PDFNon-alcoholic fatty liver disease (NAFLD) is a hepatic disease associated with metabolic syndrome. NAFLD covers a spectrum of liver disease from steatosis to non-alcoholic steatohepatitis (NASH) and cirrhosis. NASH is a disease evolving under the influence of various stimuli still poorly understood.
View Article and Find Full Text PDFObjective: Evidence points to a founder of the multifunctional CCN family, NOV/CCN3, as a circulating molecule involved in cardiac development, vascular homeostasis and inflammation. No data are available on the relationship between plasma NOV/CCN3 levels and cardiovascular risk factors in humans. This study investigated the possible relationship between plasma NOV levels and cardiovascular risk factors in humans.
View Article and Find Full Text PDFBackground: Roux-en-Y gastric bypass (RYGB) surgery is one of the most efficient procedures for treating morbid obesity and results in weight-loss and improvements in metabolism and inflammation.
Objective: We examined the impact of RYGB on modifications of gut microbiota and its potential associations with changes in gene expression in white adipose tissue (WAT).
Design: Gut microbiota were profiled from fecal samples by using pyrosequencing in morbidly obese individuals, explored before (0 mo), 3 mo after, and 6 mo after RYGB.
Aims: Recent studies have reported a relationship between the abundance of epicardial adipose tissue (EAT) and the risk of cardiovascular diseases including atrial fibrillation (AF). However, the underlying mechanisms are unknown. The aim of this study was to examine the effects of the secretome of human EAT on the histological properties of the myocardium.
View Article and Find Full Text PDFObjective: We investigated the impact of several genetic variants located in genes encoding for proteins involved in biogenesis, maturation, and intravascular remodeling of high density lipoprotein (HDL) particles on plasma efflux capacity.
Approach And Results: The capacity of whole-plasma to mediate cholesterol efflux from cholesterol-loaded human THP-1 macrophages was measured in 846 individuals (450 men and 396 women). We demonstrated that rs17231506 (CETP c.
The hypertrophied white adipose tissue (WAT) during human obesity produces inflammatory mediators, including cytokines (IL-6 and TNFα) and chemokines ([C-C motif] chemokine ligand 2 and IL-8). These inflammatory factors are preferentially produced by the nonadipose cells, particularly the adipose tissue infiltrating macrophages. We identified the chemokine (C-X-C motif) ligand 2 (CXCL2) by a transcriptomic approach.
View Article and Find Full Text PDFNeutral lipid storage disease with myopathy (NLSDM) is caused by a mutation in the gene encoding adipose triglyceride lipase (ATGL), and is characterized by the presence of numerous triglyceride-containing cytoplasmic droplets in type I muscle fibers. Major clinical manifestations concern the heart and skeletal muscle, and some patients also present diabetes mellitus. We report the clinical, metabolic, and whole-body nuclear magnetic resonance imaging findings of three patients with NLSDM.
View Article and Find Full Text PDFObjectives: To identify key determinants of plasma endogenous CETP activity and threshold value of plasma CETP activity associated with high cardiovascular risk.
Methods: Endogenous plasma CETP activity was measured in a total of 1403 individuals.
Results: Multivariate analysis revealed that 23.
Inappropriate mineralocorticoid receptor (MR) activation is involved in cardiac diseases. Whether and how aldosterone is involved in the deleterious effects of cardiac mineralocorticoid activation is still unclear. Mice overexpressing MR in cardiomyocytes and their controls were treated for 7 days with aldosterone, and cardiac transcriptome was analyzed.
View Article and Find Full Text PDFContext: Severe early-onset obesity with major hyperphagia associated with hypogonadotropic hypogonadism is recognized as the main clinical presentation of leptin (LEP) or LEP receptor (LEPR) gene complete deficiency. In a few reported cases, homozygous mutations have been found in patients from consanguineous families. Care of LEPR-deficient patients is complicated because they cannot benefit from LEP treatment.
View Article and Find Full Text PDFEnviron Health Perspect
February 2013
Background: Adipose tissue (AT) is involved in several physiological functions, including metabolic regulation, energy storage, and endocrine functions.
Objectives: In this review we examined the evidence that an additional function of AT is to modulate persistent organic pollutant (POP) toxicity through several mechanisms.
Methods: We reviewed the literature on the interaction of AT with POPs to provide a comprehensive model for this additional function of AT.
Low-grade chronic inflammation is a major characteristic of obesity and results from deregulated white adipose tissue function. Consequently, there is interest in identifying the underlying regulatory mechanisms and components that drive adipocyte inflammation. Here, we report that expression of the transcriptional corepressor complex subunits GPS2 and SMRT was significantly reduced in obese adipose tissue, inversely correlated to inflammatory status, and was restored upon gastric bypass surgery-induced weight loss in morbid obesity.
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