Endocrine Abstracts

Introduction: The melanocortin 4 receptor (MC4R) is the most important hypothalamic expressed G protein coupled receptor in weight regulation. Mutations in the MC4R are the most frequent genetic cause of obesity. Recently an accessory protein of the MC4R (melanocortin receptor accessory protein 2, MRAP2) was discovered that was found to play a role in body weight regulation. MRAP2 deficient mice develop early-onset obesity. The mechanisms of disturbed weight regulation is pote...

Steroid hormones and bile acids are potent regulators of metabolic phenotype. The enzyme 5β-Reductase (AKR1D1) has a crucial role in bile acid synthesis and also generates 5β-reduced dihydrosteroid metabolites, regulating intra-cellular steroid availability though the clearance of cortisol, testosterone, androstenedione and progesterone. As AKR1D1 sits at the interface of bile acid synthesis and steroid metabolism, we have hypothesised that it plays a key role in met...

Aims: Elevated levels of neurotensin (NT), a neurotransmitter and postprandial secreted intestinal hormone, are associated with an increased risk of diabetes, cardiovascular disease and breast cancer. Here we studied the regulation of circulating pro-NT (a stable NT precursor fragment) by weight loss and dietary interventions.Methods: DiOGenes is a pan-European controlled dietary intervention study in overweight adults who first lost body weight on an 8-...

Abstract: Inflammation plays a contributing role in the pathogenesis of several metabolic disorders, including type 2 diabetes and obesity. Intriguingly, obesogenic diets induce markers of hypothalamic inflammation and neuronal injury in both rodents and humans, suggesting that targeting inflammatory pathways in the hypothalamus might represent a novel strategy to control energy metabolism. Unfortunately, the majority of steroid-based anti-inflammatory drugs are fraught with a...

Duplication of the guanine nucleotide-binding protein beta subunit 3 (GNB3) gene is associated with early-onset obesity in individuals with an unbalanced chromosome translocation. Additionally, a cytosine to thymine (C825T) polymorphism in GNB3 is associated with hypertension, obesity and metabolic syndrome; however, the mechanism of GNB3-related obesity is unknown. We created BAC-transgenic mice that carry an extra copy of the human risk-allele (T) ...