title: Exercise training attenuates hepatic inflammation, fibrosis and macrophage infiltration during diet induced-obesity in mice.
abstract: Nonalcoholic steatohepatitis, which is considered the hepatic event in metabolic syndrome, was recently associated with the innate immune system. Although regular exercise reduces hepatic injury markers like serum alanine aminotransferase (ALT) levels, the mechanisms regulating the effects of exercise on steatohepatitis are unclear. This study aimed to clarify whether exercise training suppresses hepatic injury, inflammation, and fibrosis by suppressing macrophage infiltration. Male C57BL/6J (4-week old) mice were randomly divided into four groups: normal diet (ND) control (n=7), ND exercise (n=5), high-fat diet and high-fructose water (HFF) control (n=11), and HFF exercise (n=11) groups. Mice were fed the ND or HFF from 4 to 20 weeks of age. The exercise groups were trained on a motorized treadmill for 60 min/day, five times/week. The nonalcoholic fatty liver disease (NAFLD) activity score and plasma ALT activity, indicators of liver injury, were increased in HFF control mice but were attenuated in HFF exercise mice. Hepatic inflammation, indicated by hepatic tumor necrosis factor (TNF)-α levels and hepatic resident macrophage infiltration, was significantly lower in HFF exercise mice than in HFF control mice. Hepatic fibrosis markers (histological hepatic fibrosis detected by Sirius red and α-smooth muscle actin staining and tissue inhibitor of matrix metalloproteinase-1 mRNA) were attenuated in HFF exercise mice compared with HFF control mice. These results suggest that exercise training reduces hepatic inflammation, injury, and fibrosis by suppressing macrophage infiltration.
authors.affiliation: Graduate School of Sport Sciences, Waseda University, Tokorozawa, Saitama, Japan. kawanishinoriaki@akane.waseda.jp
authors.forename: Noriaki
authors.initials: N
authors.lastname: Kawanishi
authors.forename: Hiromi
authors.initials: H
authors.lastname: Yano
authors.forename: Tsubasa
authors.initials: T
authors.lastname: Mizokami
authors.forename: Masaki
authors.initials: M
authors.lastname: Takahashi
authors.forename: Eri
authors.initials: E
authors.lastname: Oyanagi
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Suzuki
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001835:Body Weight / Q000502:physiology; D018932:Chemokine CCL2 / Q000097:blood; D059305:Diet, High-Fat / Q000009:adverse effects*; D004041:Dietary Fats / Q000633:toxicity; D005234:Fatty Liver / Q000473:pathology*; D005434:Flow Cytometry; D005632:Fructose / Q000633:toxicity; D008103:Liver Cirrhosis / Q000473:pathology*; D008264:Macrophages / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000473:pathology*; D009929:Organ Size / Q000502:physiology; D010805:Physical Conditioning, Animal / Q000502:physiology*; D060888:Real-Time Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000502:physiology; D014280:Triglycerides / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D018932:Chemokine CCL2; D004041:Dietary Fats; D014280:Triglycerides; D014409:Tumor Necrosis Factor-alpha; D005632:Fructose; D000410:Alanine Transaminase