title: Novel Action of Carotenoids on Non-Alcoholic Fatty Liver Disease: Macrophage Polarization and Liver Homeostasis.
abstract: Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease. It is characterized by a wide spectrum of hepatic changes, which may progress to non-alcoholic steatohepatitis (NASH) and cirrhosis. NAFLD is considered a hepatic manifestation of metabolic syndrome; however, mechanisms underlying the onset and progression of NAFLD are still unclear. Resident and recruited macrophages are key players in the homeostatic function of the liver and in the progression of NAFLD to NASH. Progress has been made in understanding the molecular mechanisms underlying the polarized activation of macrophages. New NAFLD therapies will likely involve modification of macrophage polarization by restraining M1 activation or driving M2 activation. Carotenoids are potent antioxidants and anti-inflammatory micronutrients that have been used to prevent and treat NAFLD. In addition to their antioxidative action, carotenoids can regulate macrophage polarization and thereby halt the progression of NASH. In this review, we summarize the molecular mechanisms of macrophage polarization and the function of liver macrophages/Kupffer cells in NAFLD. From our review, we propose that dietary carotenoids, such as β-cryptoxanthin and astaxanthin, be used to prevent or treat NAFLD through the regulation of macrophage polarization and liver homeostasis.
authors.affiliation: Department of Cell Metabolism and Nutrition, Brain/Liver Interface Medicine Research Center, Kanazawa University, Kanazawa, Ishikawa 920-8640, Japan. shali0145@gmail.com.
authors.forename: Yinhua
authors.initials: Y
authors.lastname: Ni
authors.affiliation: Department of Cell Metabolism and Nutrition, Brain/Liver Interface Medicine Research Center, Kanazawa University, Kanazawa, Ishikawa 920-8640, Japan. zgf0725@gmail.com.
authors.forename: Fen
authors.initials: F
authors.lastname: Zhuge
authors.affiliation: Department of Cell Metabolism and Nutrition, Brain/Liver Interface Medicine Research Center, Kanazawa University, Kanazawa, Ishikawa 920-8640, Japan. nakanaga@staff.kanazawa-u.ac.jp.
authors.forename: Mayumi
authors.initials: M
authors.lastname: Nagashimada
authors.affiliation: Department of Cell Metabolism and Nutrition, Brain/Liver Interface Medicine Research Center, Kanazawa University, Kanazawa, Ishikawa 920-8640, Japan. tota@staff.kanazawa-u.ac.jp.
authors.forename: Tsuguhito
authors.initials: T
authors.lastname: Ota
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology; D000072743:Beta-Cryptoxanthin / Q000494:pharmacology; D002338:Carotenoids / Q000494:pharmacology*; D016764:Cell Polarity; D004195:Disease Models, Animal; D018450:Disease Progression; D006706:Homeostasis; D006801:Humans; D007728:Kupffer Cells / Q000187:drug effects* / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008262:Macrophage Activation / Q000187:drug effects*; D024821:Metabolic Syndrome / Q000188:drug therapy; D018977:Micronutrients / Q000494:pharmacology; D065626:Non-alcoholic Fatty Liver Disease / Q000188:drug therapy*; D016032:Randomized Controlled Trials as Topic; D024341:Xanthophylls / Q000494:pharmacology
chemical_list: D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D000072743:Beta-Cryptoxanthin; D018977:Micronutrients; D024341:Xanthophylls; D002338:Carotenoids; C005948:astaxanthine
keywords: NAFLD/NASH; antioxidant; astaxanthin; carotenoids; fibrosis; inflammation; insulin resistance; macrophages/Kupffer cells; β-cryptoxanthin