Voluntary exercise attenuates obesity-associated inflammation through ghrelin expressed in macrophages |
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Authors: | Kizaki Takako Maegawa Taketeru Sakurai Takuya Ogasawara Jun-etsu Ookawara Tomomi Oh-ishi Shuji Izawa Tetsuya Haga Shukoh Ohno Hideki |
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Affiliation: | aDepartment of Molecular Predictive Medicine and Sport Science, Kyorin University, School of Medicine, 6-20-2 Shinkawa, Mitaka, Tokyo 181-8611, Japan;bFaculty of Sports and Health Sciences, Japan Women’s College of Physical Education, 8-19-1 Kitakarasuyama, Setagaya-ku, Tokyo 157-8565, Japan;cLaboratory of Biochemistry, School of Pharmacy, Hyogo University of Health Sciences, 1-3-6 Minatojima, Chuo-ku, Kobe, Hyogo 650-8530, Japan;dDepartment of Respiratory Medicine, Tokyo Medical University, Ibaraki Medical Center, 3-20-1 Chuou, Ami, Inashiki, Ibaraki 300-0395, Japan;eDepartment of Sports Biochemistry, Faculty of Health and Sports Science, Doshisha University, 1-3 Tatara-Miyakodani, Kyotanabe, Kyoto 610-0394, Japan;fGraduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8573, Japan |
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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. |
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Keywords: | Voluntary exercise Obesity Inflammation Macrophage Ghrelin |
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