Searchable abstracts of presentations at key conferences in endocrinology

ea0028yep1.1 | Young endocrinologists' prize lectures | SFEBES2012

Challenging the dogma: Tissue specific regulation of insulin action

Gathercole Laura

A role for glucocorticoids (GCs) in the regulation of carbohydrate metabolism and the development of diabetes was first described over 70 years ago. Whilst there is little doubt that systemic GC excess leads to insulin resistance the tissue specific mechanisms underpinning their effect on insulin sensitivity remain to be understood. We have defined tissue specific effects of GCs on insulin sensitivity and lipid metabolism in vitro and in vivo. In skeletal myotube...

ea0056s3.2 | Bile Acid & Microbiota (Endorsed by Endocrine Connections) | ECE2018

Subclinical hypothyroidism is ‘not’ a disease (Contra)

Gathercole Laura

Thyroid diseases are common disorders. Globally, hypothyroidism is still frequently caused by iodine deficiency. In iodine sufficient areas, the most common cause of hypothyroidism is thyroid autoimmunity. Subclinical hypothyroidism is defined as elevated thyroid-stimulating hormone (TSH) levels with free thyroxine (fT4) estimates within the reference range. It is a common disorder that increases with age affecting up to 20% of the elderly, with a higher prevalence in women. S...

ea0090ep399 | Diabetes, Obesity, Metabolism and Nutrition | ECE2023

Localisation of the steroid 5β-reductase in hepatoma cells

Potter Tom , Tomlinson Jeremy , Gathercole Laura

The hepatic enzyme 5β-reductase (AKR1D1) sits at the interface between two metabolic pathways, converting steroid hormones to their inactive 5β-reduced metabolites during steroid clearance, and as a step in the synthesis of bile acids from cholesterol. Both the steroid substrates and the bile acid products of AKR1D1 are potent hormones that regulate hepatic energy metabolism and inflammation. It is not known how these two functions are spatially organised within hepa...

ea0086p200 | Metabolism, Obesity and Diabetes | SFEBES2022

The American lifestyle-induced obesity syndrome diet (ALIOS) in mice alters the diversity and composition of the gut microbiome

Potter Tom , Arvaniti Anastasia , Harris Shelley , Tomlinson Jeremy , Gathercole Laura

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 ...

ea0065p205 | Metabolism and Obesity | SFEBES2019

The American lifestyle induced obesity syndrome diet (ALIOS) in rodents recapitulates the clinical features and sexual dimorphism of NAFLD and NASH

Harris Shelley , Arvaniti Anastasia , Cox Roger , Gathercole Laura , Tomlinson Jeremy

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...

ea0034p239 | Obesity, diabetes, metabolism and cardiovascular | SFEBES2014

Upregulation of AKR1C3 expression by insulin in a human differentiated preadipocyte cell line

House Philip , O'Reilly Michael , Gathercole Laura , Tomlinson Jeremy

Polycystic ovary syndrome (PCOS) is a clinical triad of anovulation, hyperinsulinaemia, and androgen excess. Adipose androgen generation of testosterone from androstenedione by aldo-ketoreductase type 1C3 (AKR1C3) may contribute to hyperandrogenism. We hypothesised that insulin may upregulate adipose AKR1C3 expression in vitro in a human differentiated preadipocyte cell line.We analysed AKR1C3 expression in the SGBS human preadipocyte cell line....

ea0034p350 | Steroids | SFEBES2014

Upregulation of subcutaneous adipose AKR1C3 expression in obese females: evidence for depot- and sex-specific effects

O'Reilly Michael , Gathercole Laura , Arlt Wiebke , Tomlinson Jeremy

Polycystic ovary syndrome (PCOS) is a clinical triad of anovulation, insulin resistance, and androgen excess in women. Adipose androgen generation of testosterone from androstenedione by aldo-ketoreductase type 1C3 (AKR1C3) may contribute to hyperandrogenism, particularly in the setting of obesity. We aimed to determine the effects of BMI and age on AKR1C3 expression in subcutaneous (SC) and omental (OM) fat depots in both women and men.Paired SC and OM ...

ea0031p320 | Steroids | SFEBES2013

Glucocorticoids enhance insulin sensitivity in human hepatocytes

Nasiri Maryam , Bujalska Iwona , Stewart Paul , Gathercole Laura , Tomlinson Jeremy

Patients with glucocorticoids (GC) excess develop central obesity, insulin resistance and hepatic steatosis in up to 20% of cases. Current dogma suggests that GCs cause insulin resistance in all tissues. However, we have previously demonstrated that GCs induce insulin sensitisation in adipose tissue in vitro, whilst causing insulin resistance in skeletal muscle. In rodent hepatocytes, GCs enhance insulin stimulated lipogenesis but studies in human hepatocytes have not...

ea0028p333A | Steroids | SFEBES2012

Regulation of de novo lipogenesis in human liver by 5α-reductase

Nasiri Maryam , Gathercole Laura , Stewart Paul , Tomlinson Jeremy

The potent effects of glucocorticoids (GCs) upon carbohydrate metabolism are well described. However, their actions upon lipid metabolism are poorly characterized. Patients with GC excess (Cushing’s syndrome) develop central obesity, insulin resistance and hepatic steatosis in up to 20% of cases. The A-ring reductases (5α-reductase type 1 [5αR1] and type 2 [5αR2]), inactivate cortisol as well as generate dihydrotestosterone (DHT) from testosterone (T) and a...

ea0021p180 | Diabetes and metabolism | SFEBES2009

Impact of glucocorticoids upon lipogenesis and β-oxidation in skeletal muscle

Morgan Stuart , Gathercole Laura , Stewart Paul , Smith Dave , Tomlinson Jeremy

Glucocorticoid excess is characterized by increased adiposity, skeletal myopathy and insulin resistance. Although there is a strong inverse correlation between intramuscular triglyceride (IMTG) levels and insulin sensitivity, the impact of glucocorticoids upon the processes that regulate skeletal muscle lipid metabolism has not been explored.Mouse C2C12 skeletal myocytes were grown to confluence and differentiated into myotubes in chemically defined medi...