Endocrine Abstracts

Non-alcoholic fatty liver disease (NAFLD) is a spectrum of disease spanning from simple steatosis to non-alcoholic steatohepatitis (NASH) with risk of progression to fibrosis and eventually cirrhosis. Dysfunction of the gut-liver axis plays a role the progression to NASH. Intestinal damage and increased permeability can increase the delivery of pathogen-associated molecular patterns (PAMPs), such as LPS and intact bacteria, to the liver where they can activate the TLR4 signall...

Polycystic ovarian syndrome (PCOS) is one of the most common endocrine disorders affecting 6-15% of women of reproductive age. The syndrome is characterised by a variety of reproductive and metabolic features, including hyperandrogenism, chronic anovulation and hirsutism as well as insulin resistance, dyslipidaemia, and non-alcoholic fatty liver disease (NAFLD). Specifically regarding NAFLD, androgen excess is hypothesised to have a direct effect on hepatic lipid storage, thus...

Bile acids and steroid hormones are potent regulators of metabolic phenotype. 5β-reductase (AKR1D1) is highly expressed in the liver where it catalyses a fundamental step in bile acid synthesis and inactivates steroid hormones. We have previously shown that male, but not female, AKR1D1 knockout (KO) mice on a normal chow diet are leaner than wildtype littermates but are not protected against diet induced obesity. Here we investigate the impact of a high fat diet on female...

Non-alcoholic fatty liver disease (NAFLD) is a spectrum of disease ranging from simple intrahepatic lipid accumulation to fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). 5β-reductase (AKR1D1) is a liver enzyme that catalyses a fundamental step in bile acid (BA) synthesis. Both BAs and BA intermediates are established as potent regulators of metabolic and proliferative phenotype. We have hypothesised that AKR1D1 plays a crucial regulatory role in NAFLD and HCC. Hu...

The incidence of non-alcoholic fatty liver disease (NAFLD), the hepatic manifestation of the metabolic syndrome, continues to rise. NAFLD is associated with significant liver-specific and cardiovascular morbidity and mortality, including hepatocellular carcinoma (HCC). Currently, there are no licensed therapies, highlighting the importance of understanding the pathogenic mechanisms that drive the condition. Cytochrome p450 oxidoreductase (POR) plays an essential role in activa...

Non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of metabolic disease. Steroid hormones and bile acids are established regulators of metabolic phenotype. 5β-reductase (AKR1D1) is highly expressed in human liver where it inactivates steroid hormones and catalyzes a fundamental step in bile acid synthesis. We hypothesized that AKR1D1 plays a key role in hepatic metabolic homeostasis. Genetic manipulation of AKR1D1 ...

Non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of metabolic disease. Steroid hormones and bile acids are established regulators of metabolic phenotype. 5β-reductase (AKR1D1) is highly expressed in human liver where it inactivates steroid hormones and catalyzes a fundamental step in bile acid synthesis. We hypothesized that AKR1D1 plays a key role in hepatic metabolic homeostasis. Genetic manipulation of AKR1D1 ...

Bile acids (BA) are potent steroid hormones that mediate a variety of metabolic effects. They play a pivotal role in cholesterol catabolism, intestine nutrient absorption, and regulate lipid, glucose and energy metabolism. 5-Beta-Reductase (AKR1D1) is a key enzyme in the BA synthesis pathway, required for cholesterol metabolism into bile acids. We generated a novel global AKR1D1 knockout (KO) mouse which, as expected, has decreased total serum and hepatic BAs and altered BA co...

Steroid hormones and bile acids are potent regulators of metabolism. 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 metabolic h...

Non-alcoholic fatty liver disease is the hepatic manifestation of the global epidemic of metabolic disease. Steroid hormones, including glucocorticoids and sex steroids, regulate metabolic phenotype, and in addition, bile acids have recently been identified as potent metabolic regulators. 5β-reductase (AKR1D1) is predominantly expressed in the liver and is a crucial regulator of steroid hormone clearance as well as bile acid synthesis. Its role in pathogenesis of metaboli...