Endocrine Abstracts

The ability to adapt to changing environmental stimuli, such as the availability of food, is essential for the survival of species. As such, complex mechanisms have evolved to maintain metabolic homeostasis during periods of nutritional challenge. In 2007, the Fibroblast Growth Factor 21 (FGF21) was identified as a nuclear receptor-regulated hepatokine that is induced during starvation. Since then, considerable effort has been devoted to elucidate the breadth of actions of FGF...

Background: Tumour growth is critically dependent on blood perfusion, its source of oxygen and nutrients. Therefore, tumour vascularization has become an attractive target for the treatment of many cancers types. The study of endocrine-responsive tumours, in particular, needs improved platforms to screen drugs targeting vascularization that have better resolution and that do not compromise on inter-individual variability.Aim: Hence, we’ve set out to...

Background: GLP-1/glucagon dual agonists are being developed as treatments for obesity due to their combined effect of reducing food intake while increase energy expenditure. Though the effect of the dual agonist on carbohydrate and lipid metabolism is well studied, little is known about the effects on protein metabolism. This study aimed to examine the acute and chronic effects of the GLP-1/glucagon dual agonist on amino acid metabolism.Methods: The lon...

The prevalence of obesity and its associated metabolic diseases are increasing, but current treatments are ineffective or impractical. Understanding how the gut–brain axis senses nutrients to regulate appetite and glucose homeostasis may identify new drug targets and treatments. The G protein-coupled receptor 119 (GPR119) has several endogenous lipid ligands and has been proposed to act as a nutrient sensor in the gastrointestinal tract. GPR119 is expressed on enteroendoc...

Coupling the release of pituitary hormones to the developmental stage of the oocyte is essential for female fertility. It requires estrogen to have simultaneous positive and negative feedback effects on spatially-distinct regions of the hypothalamus. However, the mechanistic basis for this differential effect is not known. We have found that negative-feedback is mediated by the nuclear receptor Dax1, which is present in the arcuate hypothalamic nucleus and serves as a ligand-d...

The General Medical Council’s publication ‘Outcomes for Graduates’ places emphasis on doctors being able to integrate biomedical science, research, and scholarship with clinical practice. In response, a new paradigm of assessment was introduced for the intercalated Bachelor of Science (iBSc) in Endocrinology program at Imperial College School of Medicine. The approach involves authentic “active learning” assessments analogous to tasks encountered in a ...

The regulation of insulin and glucagon secretion has traditionally been attributed to the gut-brain axis and direct sensing of blood glucose levels by pancreatic islets. However, the enteric nervous system may directly modulate pancreatic hormone release. This study focuses on a specific population of enteric neurons that exhibit the capability to transmit signals from the gut to the pancreas, potentially revealing new pathways of metabolic regulation. The gastrointestinal tra...

Growing evidence implicates gut microbiota-derived metabolites in metabolic homeostasis. Gut microbial dysbiosis occurs in obesity, while high-fibre and high-protein diets, which improve glucose tolerance and induce weight loss, are associated with the generation of microbial metabolites. Understanding how the gut responds to microbial metabolites may identify mechanisms that induce satiety and improve glucoregulation, revealing novel therapeutic targets. Indole is generated f...

Alterations in maternal metabolism can programme disease in the offspring. Intrahepatic cholestasis of pregnancy is a liver disease of pregnancy that presents with increased maternal serum bile acids (BA) and dyslipidaemia. We aimed to investigate whether cholestatic pregnancy affects the subsequent health of the offspring. We developed a cholestatic mouse model by supplementation of a normal chow (NC) diet with 0.5% cholic acid during pregnancy. 18 weeks old female and male o...

Defending body weight is a fundamental homeostatic process. Indeed, countless studies have demonstrated weight-maintaining hyperphagia in response to either increased energy expenditure or a reduction in the caloric density of available food. The principal effector of this adaptive food intake is thought to be the adipose tissue-derived hormone, leptin. According to the classical ’adipostat’ model, the hypoleptinemia resulting from weight loss drives food intake to r...