title: Ghrelin-induced adiposity is independent of orexigenic effects.
abstract: Ghrelin is a hormone produced predominantly by the stomach that targets a number of specific areas in the central nervous system to promote a positive energy balance by increasing food intake and energy storage. In that respect, similarities exist with the effects of consuming a high-fat diet (HFD), which also increases caloric intake and the amount of stored calories. We determined whether the effects of ghrelin on feeding and adiposity are influenced by the exposure to an HFD. Chronic intracerebroventricular ghrelin (2.5 nmol/d) increased feeding in lean rats fed a low-fat control diet (CD) [192 ± 5 g (ghrelin+CD) vs. 152 ± 5 g (control i.c.v. saline+CD), P<0.001], but the combination of ghrelin plus HFD did not result in significantly greater hyperphagia [150 ± 7 g (ghrelin+HFD) vs. 136 ± 4 g (saline+HFD)]. Despite failing to increase food intake in rats fed the HFD, ghrelin nonetheless increased adiposity [fat mass increase of 14 ± 2 g (ghrelin+HFD) vs. 1 ± 1 g (saline+HFD), P<0.001] up-regulating the gene expression of lipogenic enzymes in white adipose tissue. Our findings demonstrate that factors associated with high-fat feeding functionally interact with pathways regulating the effect of ghrelin on food intake. We conclude that ghrelin's central effects on nutrient intake and nutrient partitioning can be separated and suggest an opportunity to identify respective independent neuronal pathways.
authors.affiliation: Metabolic Diseases Institute, Department of Internal Medicine, University of Cincinnati. 2180 E. Galbraith Rd., Cincinnati, OH 45237, USA. pereztdo@ucmail.uc.edu
authors.forename: Diego
authors.initials: D
authors.lastname: Perez-Tilve
authors.forename: Kristy
authors.initials: K
authors.lastname: Heppner
authors.forename: Henriette
authors.initials: H
authors.lastname: Kirchner
authors.forename: Sarah H
authors.initials: SH
authors.lastname: Lockie
authors.forename: Stephen C
authors.initials: SC
authors.lastname: Woods
authors.forename: David L
authors.initials: DL
authors.lastname: Smiley
authors.forename: Matthias
authors.initials: M
authors.lastname: Tschöp
authors.forename: Paul
authors.initials: P
authors.lastname: Pfluger
mesh_terms: D052436:Adipose Tissue, White / Q000187:drug effects / Q000502:physiology; D050154:Adiposity / Q000187:drug effects* / Q000502:physiology; D000818:Animals; D004041:Dietary Fats / Q000008:administration & dosage; D004435:Eating / Q000187:drug effects / Q000502:physiology; D054439:Ghrelin / Q000008:administration & dosage / Q000494:pharmacology* / Q000502:physiology; D006963:Hyperphagia / Q000209:etiology / Q000503:physiopathology; D007033:Hypothalamus, Middle / Q000187:drug effects / Q000502:physiology; D057967:Infusions, Intraventricular; D050155:Lipogenesis / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D008297:Male; D053486:Melanocortins / Q000037:antagonists & inhibitors / Q000502:physiology; D009479:Neuropeptides / Q000502:physiology; D051381:Rats; D020318:Rats, Long-Evans; D017208:Rats, Wistar; D018013:Receptors, Neuropeptide / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D015854:Up-Regulation
chemical_list: D004041:Dietary Fats; D054439:Ghrelin; D053486:Melanocortins; D009479:Neuropeptides; D018013:Receptors, Neuropeptide