Searchable abstracts of presentations at key conferences in endocrinology

ea0063p647 | Interdisciplinary Endocrinology 1 | ECE2019

5-Beta-reductase (AKR1D1) deletion leads to increased insulin sensitivity in mature male mice

Arvaniti Anastasia , Harris Shelley , Nikolaou Nikolaos , Hazlehurst Jonathan , Moolla Ahmad , Dempster Niall , Cox Roger , Gathercole Laura , Tomlinson Jeremy

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...

ea0049ep730 | Steroid metabolism + action | ECE2017

Gender specific metabolic phenotype in the 5β-reductase knockout mouse

Gathercole Laura , Klusonova Petra , Nikolaou Nikolaos , Hazlehurst Jonathan , Moolla Ahmad , Dempster Niall , Penning Trevor , Cox Roger , Odermatt Alex , Tomlinson Jeremy

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...

ea0041gp174 | Receptors & Signalling | ECE2016

5β-reductase (AKR1D1) is a regulator of glucose homeostasis in human hepatocytes and development of model systems to define its role in metabolic liver disease

Nikolaos Nikolaou , Dunford James , Green Charlotte , Lee Wenhwa , Lim Reina , Gathercole Laura , McKeating Jane , Oppermann Udo , Hodson Leanne , Tomlinson Jeremy

Non-alcoholic fatty liver disease is the hepatic manifestation of the global epidemic of metabolic disease. Steroid hormones, including glucocorticoids and sex steroids, regulate metabolic phenotype, and in addition, bile acids have recently been identified as potent metabolic regulators. 5β-reductase (AKR1D1) is predominantly expressed in the liver and is a crucial regulator of steroid hormone clearance as well as bile acid synthesis. Its role in pathogenesis of metaboli...

ea0041ep728 | Neuroendocrinology | ECE2016

Women with idiopathic intracranial hypertension have a distinct andro-metabolic signature compared to polycystic ovary syndrome and simple obesity

Kempegowda Punith , O'Reilly Michael , Hornby Catherine , Botfield Hannah , Taylor Angela , Hughes Beverley , Tomlinson Jeremy , Arlt Wiebke , Sinclair Alexandra

Context: Idiopathic intracranial hypertension (IIH) is characterised by elevated intracranial pressure and occurs predominantly in obese premenopausal women. Signs and symptoms of polycystic ovary syndrome (PCOS) often coexist in IIH. Here we compared the androgenic and metabolic phenotypes in IIH, PCOS and simple obesity.Patients and Methods: We studied 25 patients with IIH (mean age 34.4±9.2 years; mean BMI 37.8±5.2 kg/m2), in comp...

ea0038oc1.4 | Early Career Oral Communications | SFEBES2015

Adipose tissue-specific androgen generation fuels an adverse metabolic phenotype in patients with polycystic ovary syndrome

O'Reilly Michael , Kempegowda Punith , Gathercole Laura , Bujalska Iwona , Taylor Angela , Hughes Beverley , Dunn Warwick , Semple Robert , Tomlinson Jeremy , Arlt Wiebke

Insulin resistance and androgen excess are the cardinal features of polycystic ovary syndrome (PCOS). Severity of hyperandrogenism and metabolic dysfunction in PCOS are closely correlated, but underlying mechanisms remain poorly understood. Aldoketoreductase type 1C3 (AKR1C3) is a key source of adipose androgen generation, activating androstenedione to testosterone (T). We postulated that AKR1C3 plays a critical role linking androgen metabolism and metabolic ...

ea0038p193 | Obesity, diabetes, metabolism and cardiovascular | SFEBES2015

Women with idiopathic intracranial hypertension have a distinct andro-metabolic signature compared to polycystic ovary syndrome and simple obesity

O'Reilly Michael , Kempegowda Punith , Botfield Hannah , Ali Fizzah , Taylor Angela , Hughes Beverley , Tomlinson Jeremy , Arlt Wiebke , Sinclair Alex

Context: Idiopathic intracranial hypertension (IIH) is characterised by elevated intracranial pressure and occurs predominantly in obese premenopausal women. Signs and symptoms of polycystic ovary syndrome (PCOS) often coexist in IIH. Here we compared the androgenic and metabolic phenotypes in IIH, PCOS and simple obesity.Patients and methods: We studied 25 patients with IIH (mean age 34.4±9.2 years; mean BMI 37.8±5.2 kg/m2), in comp...

ea0038p211 | Obesity, diabetes, metabolism and cardiovascular | SFEBES2015

Longitudinal changes in adipose tissue gene expression profile are asociated with deteriorating glucose tolerance

Woods Conor , Crowley Rachel , Gathercole Laura , Hughes Beverly , Gray Joanna , McCarthy Theresa , Crabtree Nicola , Stewart Paul , Tomlinson Jeremy

Increased adiposity is associated with insulin resistance, type 2 diabetes and metabolic dysfunction. Altered adipokine secretion, changes in local and systemic glucocorticoid metabolism and increased inflammation have all been postulated as contributory mechanisms. We have previously described changes in subcutaneous adipose tissue (SAT) gene expression that are associated with obesity and glucose intolerance in cross-sectional studies. However, the effects of longitudinal ch...

ea0038p356 | Reproduction | SFEBES2015

Visceral fat drives 5α-reductase activity independent of BMI in women with polycystic ovarian syndrome

Kempegowda Punith , O'Reilly Michael W , Crabtree Nicola J , Taylor Angela E , Hughes Beverly A , Tomlinson Jeremy W , Arlt Wiebke

Context: Androgen excess, obesity and hyperinsulinaemia are the cardinal features of polycystic ovarian syndrome (PCOS). While several studies have addressed the relationship between androgen excess and hyperinsulinaemia, the link between androgen excess and fat distribution remains largely undefined. Recent work has highlighted the importance of adipose tissue as an organ of androgen activation. Here, we evaluated the relationship between visceral fat and androgen excess in w...

ea0038p396 | Steroids | SFEBES2015

Model systems to define the role of AKR1D1 in metabolic liver disease

Nikolaou Nikolaos , Gathercole Laura , Dunford James , Lee Wenhwa , Lim Reina , McKeating Jane , Oppermann Udo , Hodson Leanne , Tomlinson Jeremy

Non-alcoholic fatty liver disease is the hepatic manifestation of the global epidemic of metabolic disease. It is tightly associated with obesity and type 2 diabetes, yet the precise mechanisms that drive its aetiology are not fully defined. Steroid hormones, including glucocorticoids and sex steroids, regulate metabolic phenotype, and in addition, bile acids have recently been identified as potent metabolic regulators. AKR1D1 (5β-reductase), is predominantly expressed in...

ea0038p399 | Steroids | SFEBES2015

Glucocorticoid-induced lipolysis across human ageing and the relationship to fat mass and androgens

Hassan-Smith Zaki , Taylor Angela , Hughes Beverly , Brady Theresa , Jones Pamela , Morgan Stuart , Lavery Gareth , Tomlinson Jeremy , Stewart Paul

Background: Excess glucocorticoid (GC) exposure is associated with an adverse body composition and metabolic profile characterised by increasing fat mass, muscle atrophy, insulin resistance, fatty liver, and dyslipidaemia culminating in increased cardiovascular risk. GCs are widely prescribed with increasing age where their effects can have deleterious effects.Objectives: To investigate the impact of GC exposure on subcutaneous adipose lipid metabolism a...