Location: Children's Nutrition Research CenterTitle: Thermogenic characterization of ghrelin receptor null mice Author
|Lin, Ligen - Children's Nutrition Research Center (CNRC)|
|Sun, Yuxiang - Children's Nutrition Research Center (CNRC)|
Submitted to: Methods in Enzymology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 6/17/2013
Publication Date: 6/17/2012
Citation: Lin, L., Sun, Y. 2012. Thermogenic characterization of ghrelin receptor null mice. Methods in Enzymology. 514:355-370.
Interpretive Summary: Ghrelin is the only hormone known to increase appetite and promote obesity. In this paper, we used various experimental approaches to show that the ghrelin receptor (growth hormone secretagogue receptor, GHS-R) controls body composition by regulating heat-production in brown fat. Mice with GHS-R deletion have higher energy expenditure, which subsequently results in reduced body fat and improved responsiveness to insulin. Intriguingly, the mice with GHS-R deletion had similar food intake and physical activity. Further molecular analysis revealed that deletion of GHS-R enhances fat burning (to produce more heat) in brown fat, while promotes fat depletion in white fat. Hence, GHS-R is a major player for regulation of energy balance in the body, which modulates the "Yin-Yang" balance of white and brown fat. These new observations suggest that GHS-R blockers may represent a novel approach to combat obesity without the need for dieting or exercise.
Technical Abstract: Ghrelin is the only known circulating orexigenic hormone that increases food intake and promotes adiposity, and these physiological functions of ghrelin are mediated through its receptor growth hormone secretagogue receptor (GHS-R). Ghrelin/GHS-R signaling plays a crucial role in energy homeostasis. Old GHS-R null mice exhibit a healthy phenotype-lean and insulin sensitive. Interestingly, the GHS-R null mice have increased energy expenditure, yet exhibit no difference in food intake or locomotor activity compared to wild-type mice. We have found that GHS-R is expressed in brown adipose tissue (BAT) of old mice. Ablation of GHS-R attenuates age-associated decline in thermogenesis, exhibiting a higher core body temperature. Indeed, the BAT of old GHS-R null mice reveals enhanced thermogenic capacity, which is consistent with the gene expression profile of increases in glucose/lipid uptake, lipogenesis, and lipolysis in BAT. The data collectively suggest that ghrelin/GHS-R signaling has important roles in thermogenesis. The recent discovery that BAT also regulates energy homeostasis in adult humans makes the BAT a new antiobesity target. Understanding the roles and molecular mechanisms of ghrelin/GHS-R in thermogenesis is of great significance. GHS-R antagonists might be a novel means of combating obesity by shifting adiposity balance from obesogenesis to thermogenesis.