Endocrine Abstracts

Urocortins are the endogenous ligands for the corticotropin-releasing factor receptor type-2 which is highly expressed in skeletal muscle where it regulates glucose metabolism and muscle mass. Transgenic mice overexpressing Urocortin-3 (UCN3+) show accelerated peripheral glucose disposal and increased skeletal muscle mass with myocyte hypertrophy associated with decreased energy efficiency and improved glucose tolerance. We aimed to determine whether this phenotype would confe...

Background: In mice, a methionine-choline deficient diet (MCDD) causes steatohepatitis and hepatic insulin resistance. In contrast, a simple choline-deficient diet (CDD) causes liver fat accumulation without steatohepatitis, insulin resistance or weight loss. We hypothesised that differences in liver and adipose fatty acid metabolism underlie the contrasting predisposition to steatohepatitis and hepatic insulin resistance.Methods: C57Bl6 mice (male, aged...

Glucocorticoid metabolism is altered in a tissue-specific manner in obesity. Increased reactivation of glucocorticoids by 11beta-hydroxysteroid dehydrogenase type 1 (11HSD1) amplifies glucocorticoid action in abdominal fat, whereas increased metabolism of glucocorticoids by hepatic A-ring reductases may contribute to activation of the hypothalamic-pituitary-adrenal axis. These changes have been characterised in leptin-resistant obese Zucker rats and obese humans. Here we inves...

Obese humans and rats exhibit altered glucocorticoid metabolism; increased regeneration of glucocorticoid by adipose 11HSD1 and inactivation by hepatic A-ring reductases. The mechanisms remain unclear; candidates include resistance to insulin-mediated regulation, and secondary effects of adipose products eg TNFalpha. To explore temporal associations between changes in glucocorticoid metabolism, insulin resistance and obesity, we examined effects of high-fat feeding in rats.<br...

Metabolic Syndrome (visceral obesity, insulin resistance, type2 diabetes) resembles Cushing's syndrome, but lacks elevated circulating cortisol levels. This has engendered the hypothesis that excessive local glucocorticoid regeneration, resulting from elevated adipose 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD-1) underlies the Metabolic Syndrome. We report that 11beta-HSD-1 nullizygosity (11beta-HSD-1-/-) reduced intra-adipose corticosterone levels and i...