title: Ghrelin receptor regulates adipose tissue inflammation in aging.
abstract: Aging is commonly associated with low-grade adipose inflammation, which is closely linked to insulin resistance. Ghrelin is the only circulating orexigenic hormone which is known to increase obesity and insulin resistance. We previously reported that the expression of the ghrelin receptor, growth hormone secretagogue receptor (GHS-R), increases in adipose tissues during aging, and old Ghsr(-/-) mice exhibit a lean and insulin-sensitive phenotype. Macrophages are major mediators of adipose tissue inflammation, which consist of pro-inflammatory M1 and anti-inflammatory M2 subtypes. Here, we show that in aged mice, GHS-R ablation promotes macrophage phenotypical shift toward anti-inflammatory M2. Old Ghsrp(-/-) mice have reduced macrophage infiltration, M1/M2 ratio, and pro-inflammatory cytokine expression in white and brown adipose tissues. We also found that peritoneal macrophages of old Ghsrp(-/-) mice produce higher norepinephrine, which is in line with increased alternatively-activated M2 macrophages. Our data further reveal that GHS-R has cell-autonomous effects in macrophages, and GHS-R antagonist suppresses lipopolysaccharide (LPS)-induced inflammatory responses in macrophages. Collectively, our studies demonstrate that ghrelin signaling has an important role in macrophage polarization and adipose tissue inflammation during aging. GHS-R antagonists may serve as a novel and effective therapeutic option for age-associated adipose tissue inflammation and insulin resistance.
authors.affiliation: USDA/ARS Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA.|State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, China.
authors.forename: Ligen
authors.initials: L
authors.lastname: Lin
authors.affiliation: USDA/ARS Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Jong Han
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine at University of Michigan Health System, Ann Arbor, MI 48109, USA.
authors.forename: Eric D
authors.initials: ED
authors.lastname: Buras
authors.affiliation: Department of Intensive Care Unit, the Third Affiliated Hospital, Harbin Medical University, Harbin, 150081, China.
authors.forename: Kaijiang
authors.initials: K
authors.lastname: Yu
authors.affiliation: Department of Intensive Care Unit, the Third Affiliated Hospital, Harbin Medical University, Harbin, 150081, China.
authors.forename: Ruitao
authors.initials: R
authors.lastname: Wang
authors.affiliation: USDA/ARS Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: C Wayne
authors.initials: CW
authors.lastname: Smith
authors.affiliation: Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Huaizhu
authors.initials: H
authors.lastname: Wu
authors.affiliation: Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA.|Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: David
authors.initials: D
authors.lastname: Sheikh-Hamad
authors.affiliation: USDA/ARS Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA.|Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA.|Huffington Center on Aging, Baylor College of Medicine, Houston, TX 77030, USA.|Department of Nutrition and Food Science, Texas AandM University, College Station, TX 77843, USA.
authors.forename: Yuxiang
authors.initials: Y
authors.lastname: Sun
mesh_terms: D000367:Age Factors; D000375:Aging / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D000066670:Cell Plasticity; D020022:Genetic Predisposition to Disease; D006727:Hormone Antagonists / Q000494:pharmacology; D018836:Inflammation Mediators / Q000378:metabolism; D007333:Insulin Resistance; D050152:Intra-Abdominal Fat / Q000187:drug effects / Q000378:metabolism*; D008066:Lipolysis; D008070:Lipopolysaccharides / Q000494:pharmacology; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D015434:Panniculitis / Q000235:genetics / Q000378:metabolism* / Q000517:prevention & control; D010641:Phenotype; D000067996:RAW 264.7 Cells; D054440:Receptors, Ghrelin / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*
chemical_list: D000893:Anti-Inflammatory Agents; D006727:Hormone Antagonists; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D054440:Receptors, Ghrelin; C000592182:Ghsr protein, Mouse
keywords: adipose tissue macrophages (ATMs); ghrelin; growth hormone secretagogue receptor (GHS-R); inflammation; peritoneal macrophages (PM); thermogenesis
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