Endocrine Abstracts

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</...

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...

Insulin-resistant diabetes is characterised by progressive pancreatic β-cell dysfunction. Elevated pancreatic islet activity of the intracellular glucocorticoid amplifying enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) was hypothesized to drive this process in genetically obese rodents. To determine the direct effects of elevated 11β-HSD1 on β-cell function in diabetes in vivo we created a transgenic model overexpressing 11β-HSD1...

Deficiency of the intracellular glucocorticoid (GC) reactivating enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) invokes compensatory activation of the HPA axis. Nevertheless, 11β-HSD1−/− mice resist dietary-induced obesity indicating that target tissues are protected from GC actions. Since endocrine adaptation to diet is mediated by altered HPA activity, we investigated whether the adrenal response to high fat (HF) diet is compr...

High systemic cortisol levels contribute to insulin resistance and may exacerbate the development of diabetes by impairing the insulin secretory response of the pancreatic beta-cells (β-cells). 11β-Hydroxysteroid dehydrogenase type 1 (11β-HSD1) is a key modulator of glucocorticoid effect within target tissues and high adipose or liver levels of this enzyme may contribute to obesity and/or metabolic disease. We investigated cellular localization of 11β-HSD1 ...

Brown adipose tissue (BAT) is a therapeutic target for obesity and associated metabolic diseases, due to its role in non-shivering thermogenesis. BAT activation is mediated through sympathetic stimulation, but parasympathetic regulation of human BAT has not been demonstrated previously. We undertook RNA sequencing of human white and brown primary adipocytes to identify novel pathways regulating BAT. CHRM2 (encoding the muscarinic acetylcholine receptor 2) was the most differen...

The recent discovery of brown adipose tissue (BAT) in adult humans, which generates heat to maintain body temperature in a cold environment, offers an exciting new strategy to treat obesity and metabolic disease, but our knowledge of human BAT activation is limited. To identify novel pathways regulating human BAT, we undertook RNA sequencing of human brown and white adipocytes. The gene SLC6A4 (encoding the serotonin transporter SERT) was one of the most highly differ...

Background: 18F-fluorodeoxyglucose (18FDG) PET is commonly used to quantify brown adipose tissue (BAT) mass/activity in humans but requires cold exposure. Rodent brown (BAds) but not white adipocytes (WAds) exhibit high choline content, thus we hypothesised that human BAT would demonstrate substantial 18F-fluorocholine (18FCH) uptake in vivo during warm and cold conditions.Methods: (1)...