title: The Ghrelin/GOAT System Regulates Obesity-Induced Inflammation in Male Mice.
abstract: Ghrelin plays a key role in appetite, energy homeostasis, and glucose regulation. Recent evidence suggests ghrelin suppresses inflammation in obesity; however, whether this is modulated by the acylated and/or des-acylated peptide is unclear. We used mice deficient in acylated ghrelin [ghrelin octanoyl-acyltransferase (GOAT) knockout (KO) mice], wild-type (WT) littermates, and C57BL/6 mice to examine the endogenous and exogenous effects of acyl and des-acyl ghrelin on inflammatory profiles under nonobese and obese conditions. We demonstrate that in the spleen, both ghrelin and GOAT are localized primarily in the red pulp. Importantly, in the thymus, ghrelin was predominantly localized to the medulla, whereas GOAT was found in the cortex, implying differing roles in T cell development. Acute exogenous treatment with acyl/des-acyl ghrelin suppressed macrophage numbers in spleen and thymus in obese mice, whereas only acyl ghrelin increased CD3+ T cells in the thymus in mice fed both chow and a high-fat-diet (HFD). Consistent with this result, macrophages were increased in the spleen of KO mice on a HFD. Whereas there was no difference in CD3+ T cells in the plasma, spleen, or thymus of WT vs KO mice, KO chow and HFD-fed mice displayed decreased leukocytes. Our results suggest that the acylation status affects the anti-inflammatory properties of ghrelin under chow and HFD conditions.
authors.affiliation: Department of Physiology, Monash Biomedicine Discovery Institute, Monash University, Clayton, Melbourne, Victoria 3800, Australia.
authors.forename: Rebecca E
authors.initials: RE
authors.lastname: Harvey
authors.affiliation: Department of Physiology, Monash Biomedicine Discovery Institute, Monash University, Clayton, Melbourne, Victoria 3800, Australia.
authors.forename: Victor G
authors.initials: VG
authors.lastname: Howard
authors.affiliation: Department of Physiology, Monash Biomedicine Discovery Institute, Monash University, Clayton, Melbourne, Victoria 3800, Australia.
authors.forename: Moyra B
authors.initials: MB
authors.lastname: Lemus
authors.affiliation: Department of Physiology, Monash Biomedicine Discovery Institute, Monash University, Clayton, Melbourne, Victoria 3800, Australia.
authors.forename: Tara
authors.initials: T
authors.lastname: Jois
authors.affiliation: Department of Physiology, Monash Biomedicine Discovery Institute, Monash University, Clayton, Melbourne, Victoria 3800, Australia.
authors.forename: Zane B
authors.initials: ZB
authors.lastname: Andrews
authors.affiliation: Department of Physiology, Monash Biomedicine Discovery Institute, Monash University, Clayton, Melbourne, Victoria 3800, Australia.|Department of Biochemistry and Molecular Biology, Monash University, Clayton, Melbourne, Victoria 3800, Australia.
authors.forename: Mark W
authors.initials: MW
authors.lastname: Sleeman
mesh_terms: D000217:Acyltransferases / Q000235:genetics / Q000502:physiology*; D000818:Animals; D059305:Diet, High-Fat; D054439:Ghrelin / Q000502:physiology*; D007249:Inflammation / Q000209:etiology* / Q000235:genetics / Q000276:immunology; D008297:Male; D008565:Membrane Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008820:Mice, Obese; D009765:Obesity / Q000150:complications* / Q000235:genetics; D013154:Spleen / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000502:physiology; D013950:Thymus Gland / Q000276:immunology / Q000378:metabolism
chemical_list: D054439:Ghrelin; D008565:Membrane Proteins; C422650:ghrelin, des-n-octanoyl; D000217:Acyltransferases; C526983:Mboat4 protein, mouse