Searchable abstracts of presentations at key conferences in endocrinology

ea0081p370 | Diabetes, Obesity, Metabolism and Nutrition | ECE2022

Differential localisation of the A-ring reductases in human hepatocytes: implications for substrate preference and utilisation

Potter Tom , da Conceicao Ismael , Nikolaou Nikolaos , Loh Nellie , Tomlinson Jeremy , Gathercole Laura

The 5-reductases are steroid metabolising enzymes that saturate the C4=C5 bond of the steroid A-ring, and their substrates include androgens, glucocorticoids, and bile acids. 5β-reductases (SRD5A1 & SRD5A2) convert testosterone to the more potent androgen 5β-dihydrotestosterone, and carry out the first step in glucocorticoid clearance, generating 5β-dihydrocortisol from cortisol. 5β-reductase (AKR1D1) is also able to carry out the first step of glucocor...

ea0050oc1.2 | Early Career Oral Communications | SFEBES2017

Co-administration of 5α-reductase inhibitors worsens the adverse metabolic effects of prescribed glucocorticoids

Marjot Tom , Othonos Nantia , Woods Conor , Hazlehurst Jonathan , Moolla Ahmad , Hodson Leanne , Tomlinson Jeremy

Glucocorticoids (GC) are commonly prescribed and their use is associated with adverse metabolic side effects. 5a-reductase (5aR) inhibitors are also frequently prescribed mainly for their ability to inhibit the conversion of testosterone to dihydrotestosterone. However, they also have a role to inactivate and clear GCs. We hypothesised that 5aR inhibitors have the potential to exacerbate the adverse metabolic effects of GCs. We conducted a prospective, randomised, study in 19 ...

ea0050p206 | Diabetes and Cardiovascular | SFEBES2017

The impact of a dedicated metabolic hepatology clinic for the treatment of non-alcoholic fatty liver disease

Motohashi Kenzo , Moolla Ahmad , Marjot Tom , Ainsworth Mark , Tomlinson Jeremy , Cobbold Jeremy

Introduction: Non-Alcoholic Fatty Liver Disease (NAFLD) is the hepatic manifestation of metabolic syndrome and is tightly associated with insulin resistance and type 2 diabetes (T2DM), both risk factors for disease progression, liver failure and cardiovascular complications. A multidisciplinary approach involving hepatologists and diabetologists working alongside allied health professionals is thus advocated for the management of NAFLD. Interv...

ea0050p319 | Obesity and Metabolism | SFEBES2017

The adverse metabolic phenotype associated with obstructive sleep apnoea is not driven by activation of the hypothalamo-pituitary-adrenal axis

Hazlehurst Jonathan M , Charlton Catriona , Mantripp Diana , Hodson Leanne , Tomlinson Jeremy W

Glucocorticoid (GC) excess drives obesity, insulin resistance and type 2 diabetes. Obstructive sleep apnoea (OSA) is a prevalent condition associated with both activation of the hypothalamic-pituitary-adrenal (HPA) axis and an adverse metabolic phenotype. However, a causal link between these two features has not been established. We designed a novel human model of intermittent hypoxia (IH) aimed at replicating the systemic insulin resistance associ...

ea0050oc1.2 | Early Career Oral Communications | SFEBES2017

Co-administration of 5α-reductase inhibitors worsens the adverse metabolic effects of prescribed glucocorticoids

Marjot Tom , Othonos Nantia , Woods Conor , Hazlehurst Jonathan , Moolla Ahmad , Hodson Leanne , Tomlinson Jeremy

Glucocorticoids (GC) are commonly prescribed and their use is associated with adverse metabolic side effects. 5a-reductase (5aR) inhibitors are also frequently prescribed mainly for their ability to inhibit the conversion of testosterone to dihydrotestosterone. However, they also have a role to inactivate and clear GCs. We hypothesised that 5aR inhibitors have the potential to exacerbate the adverse metabolic effects of GCs. We conducted a prospective, randomised, study in 19 ...

ea0050p206 | Diabetes and Cardiovascular | SFEBES2017

The impact of a dedicated metabolic hepatology clinic for the treatment of non-alcoholic fatty liver disease

Motohashi Kenzo , Moolla Ahmad , Marjot Tom , Ainsworth Mark , Tomlinson Jeremy , Cobbold Jeremy

Introduction: Non-Alcoholic Fatty Liver Disease (NAFLD) is the hepatic manifestation of metabolic syndrome and is tightly associated with insulin resistance and type 2 diabetes (T2DM), both risk factors for disease progression, liver failure and cardiovascular complications. A multidisciplinary approach involving hepatologists and diabetologists working alongside allied health professionals is thus advocated for the management of NAFLD. Interv...

ea0050p319 | Obesity and Metabolism | SFEBES2017

The adverse metabolic phenotype associated with obstructive sleep apnoea is not driven by activation of the hypothalamo-pituitary-adrenal axis

Hazlehurst Jonathan M , Charlton Catriona , Mantripp Diana , Hodson Leanne , Tomlinson Jeremy W

Glucocorticoid (GC) excess drives obesity, insulin resistance and type 2 diabetes. Obstructive sleep apnoea (OSA) is a prevalent condition associated with both activation of the hypothalamic-pituitary-adrenal (HPA) axis and an adverse metabolic phenotype. However, a causal link between these two features has not been established. We designed a novel human model of intermittent hypoxia (IH) aimed at replicating the systemic insulin resistance associ...

ea0086oc5.2 | Metabolism, Obesity and Diabetes | SFEBES2022

7α-hydroxy-3-oxo-4-cholestenoic acid (7-HOCA) is a novel AKR1D1 substrate driving metabolic dysfunction and hepatocellular cancer risk in patients with non-alcoholic fatty liver disease (NAFLD)

Nikolaou Nikolaos , Arvaniti Anastasia , Sanna Fabio , da Conceicao Ismael , Dempster Niall , Gathercole Laura , Tomlinson Jeremy

Non-alcoholic fatty liver disease (NAFLD) is a spectrum of disease ranging from intrahepatic lipid accumulation to fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). Liver 5β-reductase (AKR1D1) catalyses a fundamental step in bile acid (BA) synthesis. BAs and BA intermediates are potent regulators of metabolic and proliferative phenotype. We have hypothesised that AKR1D1 plays a crucial role in NAFLD and HCC. Liver biopsies and serum samples were obtained from healt...