Role of genetic variation in the cannabinoid type 1 receptor gene (CNR1) in the pathophysiology of human obesity.

Aims: The endocannabinoid system may contribute to the association of visceral fat accumulation with metabolic diseases. Here we investigated the effects of genetic variation in the cannabinoid type 1 receptor gene (CNR1) on its mRNA expression in adipose tissue from visceral and subcutaneous depots and on the development of obesity.

Materials & Methods: CNR1 was sequenced in 48 nonrelated German Caucasians to detect genetic variation.

Effect of genetic variation in the human fatty acid synthase gene (FASN) on obesity and fat depot-specific mRNA expression.

Inhibition of fatty acid synthase (FASN) induces a rapid decline in fat stores in mice, suggesting a role for this enzyme in energy homeostasis. To investigate the potential role of FASN in the pathophysiology of human obesity, the FASN gene was sequenced in 48 German whites. Thirty-five single-nucleotide polymorphisms (SNPs) were identified.

TCF7L2 gene expression in human visceral and subcutaneous adipose tissue is differentially regulated but not associated with type 2 diabetes mellitus.

Variants in the TCF7L2 gene have been associated with type 2 diabetes mellitus (T2DM), but the causal variant(s) is still unknown. We studied the TCF7L2 messenger RNA (mRNA) expression in paired samples of visceral and subcutaneous adipose tissue from 49 subjects using quantitative real-time polymerase chain reaction and its relation to obesity and T2DM. All subjects were genotyped for the previously described TCF7L2 diabetes risk variants.

Gene expression of adiponectin receptors in human visceral and subcutaneous adipose tissue is related to insulin resistance and metabolic parameters and is altered in response to physical training.

Objective: Adiponectin receptors 1 and 2 (AdipoR1 and AdipoR2, respectively) mediate the effects of adiponectin on glucose and lipid metabolism in vivo. We examined whether AdipoR1 and/or AdipoR2 mRNA expression in human adipose tissue is fat-depot specific. We also studied whether their expression in visceral and subcutaneous fat depots is associated with metabolic parameters and whether their expression is regulated by intensive physical exercise.

Effects of genetic variation in the human retinol binding protein-4 gene (RBP4) on insulin resistance and fat depot-specific mRNA expression.

Objective: Serum retinol binding protein 4 (RBP4) is a new liver- and adipocyte-derived signal that may contribute to insulin resistance. Therefore, the RBP4 gene represents a plausible candidate gene involved in susceptibility to type 2 diabetes.

Research Design And Methods: In this study, the RBP4 gene was sequenced in DNA samples from 48 nonrelated Caucasian subjects.

Serum retinol-binding protein is more highly expressed in visceral than in subcutaneous adipose tissue and is a marker of intra-abdominal fat mass.

Intra-abdominal fat is associated with insulin resistance and cardiovascular risk. Levels of serum retinol-binding protein (RBP4), secreted by fat and liver cells, are increased in obesity and type 2 diabetes (T2D). Here we report that, in 196 subjects, RBP4 is preferentially expressed in visceral (Vis) versus subcutaneous (SC) fat.

TCF7L2 gene polymorphisms confer an increased risk for early impairment of glucose metabolism and increased height in obese children.

Context: Variants in the transcription factor 7-like2 (TCF7L2) gene have been associated with an increased risk for type 2 diabetes in adults. To evaluate whether the five reported risk variants confer a higher risk for obesity and early impairment of glucose metabolism in children, we genotyped these risk variants of the TCF7L2 gene in a representative cohort of 1029 Caucasian children and an independent cohort of 283 obese children.

Results: Applying a case control design, we observed a significantly lower prevalence of the rs11196205 and rs7895340 risk alleles in the obese (n = 283) compared with lean (n = 672) children (0.

Dysregulation of the peripheral and adipose tissue endocannabinoid system in human abdominal obesity.

The endocannabinoid system has been suspected to contribute to the association of visceral fat accumulation with metabolic diseases. We determined whether circulating endocannabinoids are related to visceral adipose tissue mass in lean, subcutaneous obese, and visceral obese subjects (10 men and 10 women in each group). We further measured expression of the cannabinoid type 1 (CB(1)) receptor and fatty acid amide hydrolase (FAAH) genes in paired samples of subcutaneous and visceral adipose tissue in all 60 subjects.

Genetic variation in the visfatin gene (PBEF1) and its relation to glucose metabolism and fat-depot-specific messenger ribonucleic acid expression in humans.

Context And Objective: Visfatin is a peptide suggested to play a role in glucose homeostasis. In the present study, we investigated the role of genetic variation in the visfatin gene in the pathophysiology of obesity/type 2 diabetes mellitus (T2DM).

Design: The visfatin gene (PBEF1) was sequenced in DNA samples from 24 nonrelated Caucasian subjects.

Evidence for a role of developmental genes in the origin of obesity and body fat distribution.

Obesity, especially central obesity, is a hereditable trait associated with a high risk for development of diabetes and metabolic disorders. Combined gene expression analysis of adipocyte- and preadipocyte-containing fractions from intraabdominal and subcutaneous adipose tissue of mice revealed coordinated depot-specific differences in expression of multiple genes involved in embryonic development and pattern specification. These differences were intrinsic and persisted during in vitro culture and differentiation.

Vaspin gene expression in human adipose tissue: association with obesity and type 2 diabetes.

Recently, vaspin was identified as an adipokine with insulin-sensitizing effects, which is predominantly secreted from visceral adipose tissue in a rat model of type 2 diabetes. In this study, we examined whether vaspin mRNA expression is a marker of visceral obesity and correlates with anthropometric and metabolic parameters in paired samples of visceral and subcutaneous adipose tissue from 196 subjects with a wide range of obesity, body fat distribution, insulin sensitivity, and glucose tolerance. Vaspin mRNA expression was only detectable in 23% of the visceral and in 15% of the subcutaneous (SC) adipose tissue samples.

Plasma visfatin concentrations and fat depot-specific mRNA expression in humans.

Visceral and subcutaneous adipose tissue display important metabolic differences that underlie the association of visceral obesity with obesity-related cardiovascular and metabolic alterations. Recently, visfatin was identified as an adipokine, which is predominantly secreted from visceral adipose tissue both in humans and mice. In this study, we examined whether visfatin plasma concentrations (using enzyme immunosorbent assay) and mRNA expression (using RT-PCR) in visceral and subcutaneous fat correlates with anthropometric and metabolic parameters in 189 subjects with a wide range of obesity, body fat distribution, insulin sensitivity, and glucose tolerance.