Endocrine Abstracts

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...

Disruption of the gut-liver axis contributes to metabolic syndrome and the progression of non-alcoholic fatty liver disease (NAFLD). Bile acids (BAs) are potent antimicrobials that support gastrointestinal health and dysregulation of BA homeostasis in NAFLD is thought to contribute to gut dysbiosis. Furthermore, an increase in hydrophobic (cytotoxic) BA species may directly affect gut health. We have previously shown that bile acid synthesis enzyme, 5β-reductase (AKR1D1),...

Metabolic syndrome and its hepatic manifestation, non-alcoholic fatty liver disease (NAFLD), are increasing in prevalence. Steroid hormones are established regulators of metabolic phenotype. 5β-reductase (AKR1D1) is highly expressed in human liver, inactivating steroid hormones, including glucocorticoids and androgens. The human AKR1D1 gene contains 9 exons; six splice variants have been identified and three lead to functional protein isoforms (AKR1D1-001, -0...

The enzyme 5β-reductase (AKR1D1) catalyses an essential step in bile acid synthesis. In addition, it controls intra-cellular steroid hormone availability through hormone clearance. As disturbances in steroid hormones and bile acid metabolism have potent effects on metabolic health, we hypothesize that AKR1D1 may play a role hepatic lipid accumulation. We generated global AKR1D1 knockout mice (KO) alongside wild-type controls (WT). Mice were fed either normal chow (NC) or ...

The enzyme 5β-reductase (AKR1D1) catalyses an essential step in bile acid synthesis, but in addition, controls intra-cellular steroid hormone availability by generating 5β-reduced dihydrosteroid metabolites. As disturbances in steroid hormone and bile acid metabolism have potent effects on metabolic health and lipid homeostasis, we hypothesize that AKR1D1 may play a role hepatic lipid accumulation and contribute to the development of metabolic disease. We generated a...

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

Non-alcoholic fatty liver disease is the hepatic manifestation of metabolic disease. 5β-reductase (AKR1D1) is highly expressed in human and rodent liver where it inactivates steroid hormones and catalyzes a fundamental step in bile acid synthesis. Steroid hormones, including glucocorticoids, as well as bile acids are established regulators of metabolic phenotype. We have hypothesized that AKR1D1 plays a crucial regulatory role in hepatic metabolic homeostasis.<p class...

The enzyme 5β-reductase (AKR1D1) controls intra-cellular steroid hormone availability through hormone clearance. Additionally, it catalyses an essential step in bile acid (BA) synthesis. Disturbances in steroid hormones and BA metabolism have potent effects on metabolic health, therefore we hypothesize that AKR1D1 may play a role in metabolic homeostasis; the role of AKR1D1 in regulating glucose homeostasis and pancreatic function remains unexplored. We generated a global...

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...

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...