Searchable abstracts of presentations at key conferences in endocrinology

ea0041oc12.2 | Obesity | ECE2016

Female 5β-reductase knockout mice are protected from diet induced obesity, insulin resistance and glucose intolerance

Gathercole Laura , Chapman Matthew , Larner Dean , Klusonova Petra , Penning Trevor , Lavery Gareth , Odermatt Alex , Tomlinson Jeremy

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...

ea0038oc3.6 | Steroids and adrenal | SFEBES2015

Female 5β-reductase knockout mice are protected from diet induced obesity, insulin resistance, and glucose intolerance

Gathercole Laura , Chapman Matthew , Larner Dean , Klusonova Petra , Penning Trevor , Odermatt Alex , Lavery Gareth , Tomlinson Jeremy

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...

ea0038p395 | Steroids | SFEBES2015

Vitamin D2 vs vitamin D3: effects of total and free 25-hydroxyvitamin D on immune cells in vivo

Hernandez Ivan , Chun Rene , Larner Dean , Jemkinson Carl , Jeffery Louisa , Adams John S , Hewison Martin

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) ...

ea0034p267 | Obesity, diabetes, metabolism and cardiovascular | SFEBES2014

11β HSD1KO mice resist aged associated decline in markers of brown adipose tissue function

McCabe Emma , Doig Craig , Morgan Stuart , Larner Dean , Tomlinson Jeremy , Stewart Paul , Lavery Gareth

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...

ea0034oc3.1 | Steroids | SFEBES2014

Lack of 11β-hydroxysteroid dehydrogenase type 1 ameliorates the adverse features of Cushing's syndrome

Morgan Stuart , McCabe Emma , Gathercole Laura , Hassan-Smith Zaki , Larner Dean , Bujalska Iwona , Stewart Paul , Tominson Jeremy , Lavery Gareth

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...

ea0034p371 | Steroids | SFEBES2014

Enhanced expression of hepatic inflammatory markers in 11β-hydroxysteroid dehydrogenase type 1 knockout mice fed a steatogenic diet

Larner Dean , Morgan Stuart , Gathercole Laura , Nasiri Maryam , Guest Philip , Chapman Matthew , Tomlinson Jeremy , Stewart Paul , Lavery Gareth

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...

ea0065p201 | Metabolism and Obesity | SFEBES2019

Vitamin D-binding protein is required for the maintenance of α-cell identity and function

Viloria Katrina , Nasteska Daniela , Larner Dean , Fine Nicholas , Ashford Fiona , Heising Silke , Xavier Gabriela da Silva , Briant Linford , Flaxman Christine , Morgan Noel , Richardson Sarah , Hewison Martin , Hodson David

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 ...

ea0063p664 | Interdisciplinary Endocrinology 1 | ECE2019

Differential regulation of 5β-reductase (AKR1D1) expression and activity by glucocorticoids in human and rodent liver

Nikolaou Nikolaos , Morgan Stuart , Larner Dean , Sharp Anna , Raouf Zachariah , Hughes Beverly , Digweed Dena , Whitaker Martin , Ross Richard , Lavery Gareth , Arlt Wiebke , Gathercole Laura , Tomlinson Jeremy

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...

ea0059p176 | Obesity & metabolism | SFEBES2018

A Direct Comparison of Metabolic Responses to NAD repletion in C57BL/6J and C57BL/6N diet-induced obesity mouse models

Garten Antje , Cartwright David , Oakey Lucy , Fletcher Rachel , Nasteska Daniela , Hodson David , Larner Dean , Doig Craig , Ludwig Christian , Kluckova Katarina , Lavery Gareth

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...