Endocrine Abstracts

The obesity epidemic has underlined the need for new treatments to aid weight loss and prevent the associated sequelae of obesity such as type 2 diabetes, hypertension, dyslipidaemia and cardiovascular disease. The relatively recent discovery of brown adipose tissue (BAT) in adult humans has revived interest in activating this tissue to increase energy expenditure as a novel treatment for obesity and associated metabolic disease. BAT is a thermogenic organ that generates heat ...

The obesity epidemic has underlined the need for new treatments to aid weight loss and prevent the associated cardiometabolic sequelae of obesity. The relatively recent discovery of brown adipose tissue (BAT) in adult humans has revived interest in activating this tissue to increase energy expenditure as a novel treatment for these conditions. BAT is a thermogenic organ that generates heat to maintain body temperature in a cold environment. While BAT mass and activity are redu...

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A 34-year-old lady presented with a 3 year history of central weight gain, hypertension and secondary amenorrhoea. Initial 24-hour urinary free cortisol (UFC) was raised (536 nmol/24 hr) and subsequent overnight dexamethasone suppression test (DST) was elevated at 593 nmol/L. Low and high dose DST confirmed the diagnosis of Cushing’s syndrome with a slightly unusual trend of increasing cortisol levels compared with baseline. ACTH levels were undetectable while adrenal ima...

Cortisol is regenerated from cortisone by 11βHSD1 reductase in cells from VAT. Mice overexpressing 11βHSD1 in adipocytes have more glucocorticoids in the portal vein (PV) and hepatic insulin resistance. In humans, hepatic vein (HV) sampling during D4-cortisol tracer infusion confirmed substantial splanchnic cortisol generation, and indirect modelling suggested major contributions from both liver and VAT. PV sampling in dogs, however, did not reveal cortisol release f...

PPARgamma-agonists improve insulin sensitivity and discourage visceral fat accumulation but mechanisms remain uncertain. In rodents, PPARgamma-agonists downregulate 11beta-hydroxysteroid dehydrogenase type 1 (11b-HSD1) in adipose tissue (AT), thereby potentially decreasing intra-adipose glucocorticoid (GC) concentrations. We tested whether PPARgamma-agonists regulate 11b-HSD1 in humans, and if their insulin-sensitising effect is GC-dependent.12 healthy m...

Background: Infrared thermography (IRT) can assess human brown adipose tissue (BAT) activity non-invasively. However, it remains unclear if skin temperature is altered in obesity. We compared skin temperatures of lean and obese individuals following cold exposure and studied its relationship with energy expenditure (EE).Methods: 10 lean (age 28.3±2.1y, BMI 21.5±0.4kg/m2) and 10 obese (age 28.2±2.1y, BMI 36.2±1.3kg/m2</...

Obesity increases the risk of certain cancers, especially tumours that reside close to adipose tissue (e.g. breast cancers and ovarian metastasis to omentum). Adipose tissue in obesity and tumour micro-environmentsshare a common pathogenic feature, oxygen deprivation (hypoxia, Hx). Here we hypothesised that this hypoxic microenvironment causes changes in key metabolic pathways in adipocytes leading to increased cancer cell growth. To test this, human or mouse breast (BC) and o...

Introduction: Brown adipose tissue (BAT) increases energy expenditure and is a potential therapeutic target for obesity and associated cardiometabolic disease. It is unclear whether human BAT activity is reduced in obesity, as BAT 18F-fluorodeoxyglucose uptake is reduced but BAT metabolic activity measured using11C-acetate PET is preserved. BAT thermogenesis relies on the presence of uncoupling protein 1 (UCP1), which uncouples oxidative phosphorylation f...

Intracellular cortisol is regulated by 11βHSD1. Although the field has focused on regeneration of cortisol from inert cortisone by 11β-reductase activity of 11βHSD1, we have used stable isotope tracers and arteriovenous sampling to quantify simultaneous dehydrogenase (cortisone generation) and reductase (cortisol regeneration) in human adipose and skeletal muscle. In vitro studies suggest insulin regulates this balance of reductase vs dehydrogenase acti...