Searchable abstracts of presentations at key conferences in endocrinology

ea0031p320 | Steroids | SFEBES2013

Glucocorticoids enhance insulin sensitivity in human hepatocytes

Nasiri Maryam , Bujalska Iwona , Stewart Paul , Gathercole Laura , Tomlinson Jeremy

Patients with glucocorticoids (GC) excess develop central obesity, insulin resistance and hepatic steatosis in up to 20% of cases. Current dogma suggests that GCs cause insulin resistance in all tissues. However, we have previously demonstrated that GCs induce insulin sensitisation in adipose tissue in vitro, whilst causing insulin resistance in skeletal muscle. In rodent hepatocytes, GCs enhance insulin stimulated lipogenesis but studies in human hepatocytes have not...

ea0028p333A | Steroids | SFEBES2012

Regulation of de novo lipogenesis in human liver by 5α-reductase

Nasiri Maryam , Gathercole Laura , Stewart Paul , Tomlinson Jeremy

The potent effects of glucocorticoids (GCs) upon carbohydrate metabolism are well described. However, their actions upon lipid metabolism are poorly characterized. Patients with GC excess (Cushing’s syndrome) develop central obesity, insulin resistance and hepatic steatosis in up to 20% of cases. The A-ring reductases (5α-reductase type 1 [5αR1] and type 2 [5αR2]), inactivate cortisol as well as generate dihydrotestosterone (DHT) from testosterone (T) and a...

ea0034oc3.2 | Steroids | SFEBES2014

5α-reductase is a regulator of glucocorticoid action and metabolic phenotype in human liver

Nasiri Maryam , Nikolaou Nikolaos , Parajes Silvia , Bujalska Iwona , Gathercole Laura , Tomlinson Jeremy

Patients with GC excess (Cushing’s syndrome) develop central obesity, insulin resistance and hepatic steatosis. The A-ring reductases (5α-reductase type 1 (5αR1) and 2 (5αR2)) generate dihydrotestosterone from testosterone, but importantly also inactivate cortisol and are highly expressed in human liver. We propose that 5αR may regulate GC exposure and therefore may modulate metabolic phenotype in human liver.Primary human hepato...

ea0028p307 | Steroids | SFEBES2012

Adipose depot specific regulation of insulin signalling by glucocorticoids

Gathercole Laura , Morgan Stuart , Bujalska Iwona , Nasiri Maryam , Stewart Paul , Tomlinson Jeremy

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...

ea0025p294 | Steroids | SFEBES2011

Cortisol decreases lipogenesis in human hepatocytes

Nasiri Maryam , Gathercole Laura , Hauton David , Morgan Stuart , Bujalska Iwona , Stewart Paul , Tomlinson Jeremy

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...

ea0034p363 | Steroids | SFEBES2014

Androgen receptor over expression drives lipid accumulation in human hepatocytes

Nikolaou Nikolaos , Nasiri Maryam , Gathercole Laura , Castro Silvia Parajes , Krone Nils , Valsamakis George , Mastorakos George , Tomlinson Jeremy

Non-alcoholic fatty liver disease NAFLD has been associated with androgen deficiency, yet in the majority of patients with non-alcoholic steatohepatitis NASH, androgens levels are normal. In contrast, women with polycystic ovarian syndrome PCOS, which is characterised by androgen excess, have evidence of increased liver fat. Our hypothesis is that androgen exposure to the liver may be crucial in the amount of lipid that can accumulate in hepatocytes. C3A human hepatoma cells w...

ea0034p371 | Steroids | SFEBES2014

Enhanced expression of hepatic inflammatory markers in 11β-hydroxysteroid dehydrogenase type 1 knockout mice fed a steatogenic diet

Larner Dean , Morgan Stuart , Gathercole Laura , Nasiri Maryam , Guest Philip , Chapman Matthew , Tomlinson Jeremy , Stewart Paul , Lavery Gareth

Non-alcoholic fatty liver disease (NAFLD) is characterised by intra-hepatocyte lipid accumulation. Simple steatosis, which is a reversible condition, can progress to non-alcoholic steatohepatitis (NASH), cirrhosis and eventually hepatocellular carcinoma. The aetiology of NAFLD is not fully understood and it is suggested that glucocorticoid reactivation through the activity of the 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) enzyme may promote hepatic lipid accu...

ea0037gp.04.04 | Steroids | ECE2015

Regulation of lipogenesis in human hepatocytes by androgens, glucocorticoids, and 5α-reductase

Nikolaou Nikolaos , Nasiri Maryam , Parajes Sylvia , Krone Nils , Mastorakos George , Valsamakis George , Hughes Beverly , Taylor Angela , Bujalska Iwona , Gathercole Laura , Tomlinson Jeremy

Non-alcoholic fatty liver disease (NAFLD) is rapidly becoming the commonest cause of liver cirrhosis and leading indication for liver transplant worldwide. It is tightly associated with obesity and type 2 diabetes, yet the precise mechanisms that drive its aetiology are not fully defined. Dysregulation of both glucocorticoid and androgen metabolism has been implicated in its pathogenesis. The availability of these hormones to bind and activate their receptors is mainly regulat...