Ghrelin and PYY in the regulation of energy balance and metabolism: lessons from mouse mutants

Abstract

Effective control of body weight and energy homeostasis requires stringent regulation of caloric intake and energy expenditure. Gut-brain interactions comprise a central axis for the control of energy homeostasis by integrating the intake of nutrients with an effective utilization of ingested calories either by storage or by expenditure as cellular fuel. Ghrelin, a stomach-derived peptide, is the only known circulating orexigenic hormone. It is acylated with a medium-chain fatty acid by the enzyme ghrelin O-acetyltransferase (GOAT) and displays a broad range of activity, from central control of food intake to peripheral functions such as gastric emptying and insulin secretion. PYY, a peptide produced by L cells of the small intestine and rectum, has been shown to inhibit gut motility and is proposed to stimulate a powerful central satiety response. In recent years, pharmacological studies in animals and clinical studies in humans have contributed to our knowledge of principal ghrelin and PYY actions. However, valuable findings from studies using ghrelin-deficient mice, ghrelin receptor [growth hormone secretagogue receptor-1a (GHSR1a)]-deficient mice, double-knockout mice (for ghrelin and GHSR), and GOAT-deficient or -overexpressor mice, as well as mice deficient for PYY or neuropeptide Y receptors have allowed better definition of the actual physiological functions of ghrelin and PYY. This review summarizes findings from mutant mouse studies with emphasis on respective gene knockout and transgenic animals and describes how these studies contribute to the current understanding of how endogenous ghrelin and PYY as two major representatives of endocrine gut-brain communications may regulate energy and glucose homeostasis.

Diet-induced obesity blunts the behavioural effects of ghrelin: studies in a mouse-progressive ratio task

“…Our study proves that the mouse even in a state of obesity and at 16 weeks of age at the beginning of training can more than adequately perform these tasks. This is especially important, as mouse models of obesity have become widely used in obesity research (Kirchner et al 2010;Tschöp and Heiman 2001).…”

Impact of murine intestinal apolipoprotein A-IV expression on regional lipid absorption, gene expression, and growth

“…How could this be? The distal gut contains populations of L-cells, which are specialized neuroendocrine cells that in the presence of luminal fatty acids secrete PYY and GLP-1, which are potent gastrointestinal hormones that suppress appetite ( 39 ) and increase basal metabolic rate ( 40,41 ). In C57BL6 mice fed a high-fat diet, meal-stimulated apoA-IV synthesis would both increase TG-rich lipoprotein assembly ( 44 ), suggesting that it might facilitate apoB lipidation by acting as a molecular chaperone in the early stage of apoB endoplasmic reticulum (ER) translocation.…”

“…The secretion of the gut hormones GLP-1 and PYY is stimulated by the presence of fatty acids in the lumen of the distal gut (39)(40)(41). On a chow diet, plasma GLP-1 and PYY levels were similar in C57BL6 and A4KO mice ( Fig.…”

Water Extract of Liuwei Dihuang Reduces Weight Gain and Visceral Fat in Obese Rats

“…Ghrelin is a stomach-derived peptide. It is acylated with a medium-chain fatty acid and displays a broad range of activity, from the central control of food intake to peripheral functions such as gastric emptying and insulin secretion [20][21][22][23]. PYY, a peptide produced by L cells of the small intestine and rectum.…”