Endocrine Abstracts

Metabolic syndrome (MS) is an important etiologic risk factor for the development and progression of certain cancers, including colorectal. Bile acids (BA) are potent antimicrobials that support gastrointestinal health and the dysregulation of BA homeostasis is thought to contribute to gut dysbiosis and drive endotoxemia. Furthermore, an increase in the cytotoxicity ofintestinal BA species can directly damage enterocytes and promote carcinogenesis. We have previously shown tha...

The health burden associated with non-alcoholic fatty liver disease (NAFLD), the hepatic manifestation of the metabolic syndrome, continues to escalate. Not only is NAFLD associated with significant liver-specific and cardiovascular morbidity and mortality, but patients are at risk of the development of hepatocellular carcinoma (HCC); a malignancy where the incidence continues to rise and there are very limited therapeutic strategies.Aldo-keto reductase ...

Patients with glucocorticoid (GC) excess develop insulin resistance and central obesity. We have demonstrated that GCs have tissue-specific effects on insulin sensitivity in humans, causing resistance in skeletal muscle but sensitivity in subcutaneous adipose tissue. The molecular mechanisms that underpin these differences remain poorly understood. Over the last decade small non-coding RNAs (microRNAs–miRNAs) controlling protein expression have been identified, representi...

Glucocorticoid (GC) excess, Cushing’s syndrome, is characterized by central obesity, proximal myopathy, insulin resistance and potentially type 2 diabetes mellitus. Current dogma dictates that GCs cause insulin resistance across all tissues. We have previously demonstrated that GCs cause insulin sensitization of human adipose tissue in vitro, whilst inducing insulin resistance in human skeletal muscle. No prior study has evaluated whether these observations transla...

Intra-abdominal adiposity is associated with insulin resistance and increased cardiovascular morbidity and mortality. Consequently, there is a need to identify factors involved in adipose tissue distribution. Patients with glucocorticoid (GC) excess develop a classic phenotype characterized by central, but not peripheral, obesity. Differences in gene expression between omental (om) and subcutaneous (sc) adipose tissue have been described, however, the molecular mechanisms unde...

Intra-abdominal adiposity is associated with insulin resistance and increased cardiovascular morbidity and mortality. Differences in gene expression between omental (om) and subcutaneous (sc) adipose have been described, but molecular mechanisms underpinning differences in adipose biology are not known. Patients with glucocorticoid excess, Cushing’s syndrome, develop a phenotype characterized by central obesity. We have characterized the regulation of lipogenesis by gluco...

Glucocorticoid (GC) excess (Cushing’s syndrome) is characterized by central obesity, insulin resistance and in up to 20% of cases, non-alcoholic fatty liver disease (NAFLD). NAFLD is a progressive spectrum of disease ranging from hepatic steatosis to steatohepatitis, fibrosis and cirrhosis. Many processes contribute to lipid accumulation within heaptocytes including de novo lipogenesis which includes the rate-limiting carboxylation of acetyl CoA to malonyl-CoA by a...

Patients with glucocorticoid excess develop a phenotype characterized by central obesity, however, the impact of glucocorticoids upon the processes that regulate lipid accumulation has not been fully explored. We hypothesize that intracellular generation of cortisol from cortisone by 11b-hydroxysteroid dehydrogenase type 1 (11bHSD1) is an important regulator of lipid metabolism.In adipocytes, acetyl-CoA carboxylase 1 and 2 (ACC1/2) convert acetyl-CoA to ...

Glucocorticoid (GC) excess is characterized by increased adiposity, skeletal myopathy and insulin resistance. Despite the increasing use of GCs as therapeutic agents, the molecular mechanisms that underpin GC mediated changes in insulin signalling are not clear. Within skeletal muscle, the microsomal enzyme, 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) converts inactive GC, 11-dehydrocorticosterone (A) to active corticosterone (B) and thus regulates GC availabi...

Glucocorticoid (GC) excess is characterized by increased adiposity, skeletal myopathy and insulin resistance. Despite the increasing use of GCs as therapeutic agents, the molecular mechanisms that underpin the GC mediated changes in insulin signalling are not clear. The majority of previous studies have used rodent models and have shown regulation at the level of the insulin receptor (IR), IRS-1 and PI3 kinase.Primary cultures of human skeletal myocytes ...