Central Ghrelin Regulates Peripheral Lipid Metabolism in a Growth Hormone-Independent Fashion
Open Access
- 16 July 2009
- journal article
- research article
- Published by The Endocrine Society in Endocrinology
- Vol. 150 (10), 4562-4574
- https://doi.org/10.1210/en.2009-0482
Abstract
GH plays a major role in the regulation of lipid metabolism and alterations in GH axis elicit major changes in fat distribution and mobilization. For example, in patients with GH deficiency (GHD) or in mice lacking the GH receptor, the percentage of fat is increased. In addition to the direct actions of GH on lipid metabolism, current evidence indicates that ghrelin, a stomach-derived peptide hormone with potent GH secretagogue action, increases lipogenesis in white adipose tissue (WAT) through a hypothalamic-mediated mechanism. Still, the mechanism by which GH tone modulates ghrelin actions on WAT remains unclear. Here we investigated the effect of central ghrelin administration on lipid metabolism in lipogenic tissues (liver and WAT) in the absence of GH, by using a model for the study of GHD, namely the spontaneous dwarf rat, which shows increased body fat. Our data demonstrate that central chronic ghrelin administration regulates adipose lipid metabolism, mainly in a GH-independent fashion, as a result of increased mRNA, protein expression, and activity levels of fatty acid metabolism enzymes. On the contrary, central ghrelin regulates hepatic lipogenesis de novo in a GH-independent fashion but lipid mobilization in a GH-dependent fashion because carnitine palmitoyltransferase 1 was decreased only in wild-type Lewis rats. These findings suggest the existence of a new central nervous system-based neuroendocrine circuit, regulating metabolic homeostasis of adipose tissue. Understanding the molecular mechanism underlying the interplay between GH and ghrelin and their effects on lipid metabolism will provide new strategies for the design and development of suitable drugs for the treatment of GHD, obesity, and its comorbidities.Keywords
This publication has 83 references indexed in Scilit:
- The Orexigenic Effect of Ghrelin Is Mediated through Central Activation of the Endogenous Cannabinoid SystemPLOS ONE, 2008
- Ghrelin raises [Ca2+]i via AMPK in hypothalamic arcuate nucleus NPY neuronsBiochemical and Biophysical Research Communications, 2008
- Leptin activates hypothalamic acetyl-CoA carboxylase to inhibit food intakeProceedings of the National Academy of Sciences, 2007
- Ghrelin action in the brain controls adipocyte metabolismJCI Insight, 2006
- Growth hormone receptor deficiency results in blunted ghrelin feeding response, obesity, and hypolipidemia in miceAmerican Journal of Physiology-Endocrinology and Metabolism, 2006
- Absence of ghrelin protects against early-onset obesityJCI Insight, 2005
- Expression of ghrelin receptor mRNA in the rat and the mouse brainJournal of Comparative Neurology, 2005
- Insulin signalling and the regulation of glucose and lipid metabolismNature, 2001
- DIETARYREGULATION OFEXPRESSION OFGLUCOSE-6-PHOSPHATEDEHYDROGENASEAnnual Review of Nutrition, 2001
- Mechanisms of nutritional and hormonal regulation of lipogenesisEMBO Reports, 2001