title: Voluntary exercise attenuates obesity-associated inflammation through ghrelin expressed in macrophages.
abstract: Chronic low-level inflammation is associated with obesity and a sedentary lifestyle, causing metabolic disturbances such as insulin resistance. Exercise training has been shown to decrease chronic low-level systemic inflammation in high-fat diet (HFD)-induced obesity. However, the molecular mechanisms mediating its beneficial effects are not fully understood. Ghrelin is a peptide hormone predominantly produced in the stomach that stimulates appetite and induces growth hormone release. In addition to these well-known functions, recent studies suggest that ghrelin localizes to immune cells and exerts an anti-inflammatory effect. The purpose of the current study was to investigate the role of ghrelin expressed in macrophages in the anti-inflammatory effects of voluntary exercise training. Expression of tumor necrosis factor-α (TNF-α), monocyte chemotactic protein (MCP)-1 and F4/80 was increased in adipose tissue from mice fed a HFD (HFD mice) compared with mice fed a standard diet (SD mice), whereas the expression of these inflammatory cytokines was markedly decreased in mice performing voluntary wheel running during the feeding of a HFD (HFEx mice). The expression of TNF-α was also increased in peritoneal macrophages by a HFD and exercise training inhibited the increase of TNF-α expression. Interestingly, expression of ghrelin in peritoneal macrophages was decreased by a HFD and recovered by exercise training. Suppression of ghrelin expression by siRNA increased TNF-α expression and LPS-stimulated NF-κB activation in RAW264 cells, which is a macrophage cell line. TNF-α expression by stimulation with LPS was significantly suppressed in RAW264 cells cultured in the presence of ghrelin. These results suggest that ghrelin exerts potent anti-inflammatory effects in macrophages and functions as a mediator of the beneficial effects of exercise training.
authors: Department of Molecular Predictive Medicine and Sport Science, Kyorin University, School of Medicine, 6-20-2 Shinkawa, Mitaka, Tokyo 181-8611, Japan. kizaki@ks.kyorin-u.ac.jp
authors: Takako
authors: T
authors: Kizaki
authors: Taketeru
authors: T
authors: Maegawa
authors: Takuya
authors: T
authors: Sakurai
authors: Jun-etsu
authors: JE
authors: Ogasawara
authors: Tomomi
authors: T
authors: Ookawara
authors: Shuji
authors: S
authors: Oh-ishi
authors: Tetsuya
authors: T
authors: Izawa
authors: Shukoh
authors: S
authors: Haga
authors: Hideki
authors: H
authors: Ohno
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D018932:Chemokine CCL2 / Q000378:metabolism; D054439:Ghrelin / Q000096:biosynthesis / Q000502:physiology*; D007249:Inflammation / Q000628:therapy*; D017737:Macrophages, Peritoneal / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000628:therapy*; D010805:Physical Conditioning, Animal; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D054439:Ghrelin; D014409:Tumor Necrosis Factor-alpha