Endocrine Abstracts

Dysbiosis of the gut microbiome contributes to the pathogenesis of non-alcoholic fatty liver disease (NAFLD). Reduced diversity and composition of the microbiome are associated with increased intestinal barrier permeability, increased bacterial translocation and NAFLD progression. The ALIOS diet in rodents replicates many of the metabolic and histological features of NAFLD in humans and here we report the effect of the ALIOS diet on the gut microbiome. Male and female C57BL/6 ...

Non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of metabolic syndrome, ranging from simple steatosis to the necro-inflammatory disease, non-alcoholic steatohepatitis (NASH). Development of NASH subsequently increases risk of hepatocellular carcinomas (HCC). Alongside the impact on the liver, NASH is associated with other clinical features, including insulin resistance, hyperlipidaemia and sarcopaenia. We demonstrate that mice fed the American lifestyle i...

The enzyme 5β-reductase (AKR1D1) catalyses an essential step in bile acid (BA) synthesis, but in addition, controls intra-cellular steroid hormone availability by inactivation. Steroid hormones and BA are regulators of global lipid and carbohydrate metabolism. As disturbances in steroid hormone and BA metabolism have potent effects on metabolic health, we hypothesize that AKR1D1 may play a role in metabolic homeostasis. The role of AKR1D1 in regulating glucose homeostasis...

Babies born to mothers with diabetes during pregnancy are exposed to high circulating leptin before birth and, in turn, are at increased risk of developing diabetes in later life. In pancreatic islets isolated from fetal sheep, leptin influences β-cell proliferation in a bimodal manner. This study examined the effect of exogenous leptin infusion and leptin receptor antagonism on pancreatic β-cell mass in the sheep fetus in vivo.<...

Babies born to mothers with diabetes during pregnancy are exposed to high circulating leptin before birth and, in turn, are at increased risk of developing diabetes in later life. In pancreatic islets isolated from fetal sheep, leptin influences β-cell proliferation in a bimodal manner. This study examined the effect of exogenous leptin infusion and leptin receptor antagonism on pancreatic β-cell mass in the sheep fetus in vivo.<...

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),...

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...

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...

Hormonal control of pancreatic β-cell development in the fetus during late gestation remains unclear. In fetal sheep hypothyroidism causes an increase in pancreatic β-cell mass in association with increased plasma insulin and leptin concentrations. This study investigated the effects of triiodothyronine (T3), insulin and leptin on proliferation rates in fetal ovine pancreatic β-cells in vitro.All procedures were approve...