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...

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...

Dietary fat intake is an important source of energy and in excess can drive the development of obesity. Investigating how dietary fat intake alters neuronal activity in the brain and drives behavioural changes may help us understand the mechanisms behind high fat diet induced obesity. 2-oleoyglycerol (2-OG) is a naturally occurring unsaturated long chain fatty acid produced by fat digestion in the gut and a ligand of G protein-coupled receptor 119 (GPR119). Published data has ...

Kisspeptin is integral to hypothalamo-pituitary-gonadal (HPG) axis function and overall fertility. Functional deficiency of GnRH/lH secretion in the central reproductive disease, hypothalamic amenorrhoea (HA), indicates diminished kisspeptin signalling. Clinical trials have shown kisspeptin to be a viable therapeutic intervention. However, repeated administration led to the development of tachyphylaxis and so is likely a problem for future implementation. Indeed, elevated LH r...

Background: Successful reproduction relies on integration of sensory cues of attraction with corresponding emotions and behaviours. However, the intrinsic factors integrating these fundamental aspects of human attraction with limbic and reproductive pathways have not been fully identified. Kisspeptin is a crucial activator of the reproductive axis and together with its receptor is widely expressed throughout the limbic and olfactory systems in humans suggesting a potential rol...