Endocrine Abstracts

Steroid hormones and bile acids are potent regulators of metabolic phenotype. 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 met...

Steroid hormones and bile acids are potent regulators of metabolic phenotype. 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 me...

Vitamin D metabolites such as 25-hydroxyvitamin D (25D) circulate bound primarily to vitamin D binding protein (DBP). However, for most extra-renal tissues 25D uptake is independent of DBP, even though the ‘free’ 25D fraction is very small. DBP has a lower binding affinity for 25D2 compared to 25D3. We hypothesized that this would increase serum free 25D2, with possible variations in vitamin D function. Mice were placed on diets containing equal amounts (1000 IU/kg) ...

The primary function of brown adipose tissue (BAT) is to use lipids to generate heat through uncoupling of oxidative phosphorylation in mitochondria. Glucocorticoids (GC) have a negative effect upon BAT through inhibition of uncoupling protein 1 (UCP1) expression. Similarly, it has been reported that BAT levels decline with age and have been linked to age related accumulation of body fat, leading to the idea that improving BAT function during ageing could have a beneficial rol...

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...

Glucocorticoids are widely prescribed for their anti-inflammatory properties, but have a significant adverse effect profile, leading to a Cushingoid phenotype. In the present study, we test the hypothesis that reactivation of glucocorticoids, in peripheral tissues by 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1), is a major determinant of exogenous Cushing’s syndrome.WT, global 11β-HSD1 knockout (GKO), liver-specific 11β-HSD...

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...

Aim: Vitamin D-binding protein (DBP), also known as GC-globulin, transports vitamin D metabolites and is also a major actin scavenger. While DBP serum levels, gene polymorphisms and autoantigens have been associated with diabetes risk, the underlying mechanisms remain unknown. DBP is produced by the liver, but has recently been shown to be highly expressed in pancreatic α-cells. We therefore sought to investigate the role of DBP in α-cell identity and function using ...

The prevalence of metabolic syndrome and its hepatic manifestation, non-alcoholic fatty liver disease (NAFLD), continues to escalate. Glucocorticoids (GCs) and bile acids (BAs) are established regulators of metabolic phenotype. 5β-reductase (AKR1D1) is highly expressed in human and rodent liver, where it inactivates steroid hormones and catalyses a fundamental step in BA synthesis. We have previously demonstrated that AKR1D1 modulates hepatic GC availability and GC recept...

Background and Aim: Supplementation with precursors of nicotinamide adenine dinucleotide (NAD), was shown to be beneficial in preventing metabolic dysfunction in mice, which is induced by feeding a high fat diet. We compared the effect of nicotinamide riboside (NR) supplementationon whole-body energy metabolism and mitochondrial function in two widely used diet-induced obesity mouse models.Methods: Mice were fed a high fat diet (HFD, 60% fat) or standard...