Endocrine Abstracts

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 role in NAFLD and HCC. Human liver b...

Non-alcoholic fatty liver disease (NAFLD) is a spectrum of disease ranging from intrahepatic lipid accumulation to fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). Liver 5β-reductase (AKR1D1) catalyses a fundamental step in bile acid (BA) synthesis. BAs and BA intermediates are potent regulators of metabolic and proliferative phenotype. We have hypothesised that AKR1D1 plays a crucial role in NAFLD and HCC. Liver biopsies and serum samples were obtained from healt...

Non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of metabolic syndrome. It is a spectrum of disease ranging from simple intracellular lipid accumulation and eventually progressing to cirrhosis and hepatocellular carcinoma (HCC). 5β-reductase (AKR1D1) is highly expressed in human liver and catalyzes a fundamental step in bile acid (BA) synthesis. BAs are established as potent regulators of metabolic phenotype and we have hypothesised that AKR1D1 plays...

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...

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...

Introduction: Non-Alcoholic Fatty Liver Disease (NAFLD) is reported to be common in patients undergoing bariatric surgery, but the diagnostic accuracy of non-invasive NAFLD biomarkers to stage disease and track progress longitudinally has not been assessed.Methods: 274 patients undergoing bariatric surgery were included in the study. Intra-operative liver biopsies were taken from 163 patients and histologically graded using t...

Introduction: Non-Alcoholic Fatty Liver Disease (NAFLD) is reported to be common in patients undergoing bariatric surgery, but the diagnostic accuracy of non-invasive NAFLD biomarkers to stage disease and track progress longitudinally has not been assessed.Methods: 274 patients undergoing bariatric surgery were included in the study. Intra-operative liver biopsies were taken from 163 patients and histologically graded using t...

Introduction: Non-Alcoholic Fatty Liver Disease (NAFLD), is present in over 90% of obese patients undergoing bariatric surgery. It is a spectrum of pathology ranging from steatosis through to inflammation (Non-Alcoholic Steatohepatitis, NASH) and fibrosis. Bariatric surgery is currently the most effective treatment for NAFLD, but post-operative hepatic decompensation can occur and therefore pre-operative stratification of liver disease severity is beneficial. Several non-invas...