title: Metformin Prevents Fatty Liver and Improves Balance of White/Brown Adipose in an Obesity Mouse Model by Inducing FGF21.
abstract: Obesity and its associated metabolic disorders are related to the onset of fatty liver and the balance of white adipose tissue (WAT) and brown adipose tissue (BAT). We hypothesized that metformin, an effective pharmacological treatment for type 2 diabetes, would inhibit white adipogenesis, fatty liver, and metabolic dysfunction. Metformin was treated daily for 14 weeks in a high-fat dieting C57BL/6J mice. Serum biomarkers were analyzed and protein level was assessed using confocal staining or flow cytometry. The development of lipid drops in the liver cells and white adipocyte was measured using hematoxylin and eosin or Oil Red O stains. Gene expressions were analyzed with quantitative real-time PCR. Metformin treatment decreased the body weight and improved the metabolic profile of obese mice. In obese mice, metformin also induced the expression of BAT-related markers and increased fibroblast growth factor (FGF) 21 expression in the liver and in white adipocyte. Metformin suppressed white adipocyte differentiation via induction of FGF21. Metformin improves Treg/Th17 balance in CD4+ T cells in mice with high-fat diet-induced obesity. Metformin also improves glucose metabolism and metabolic disorder. Interleukin-17 deficiency also decreases inflammation in mice. Therefore, metformin may be therapeutically useful for the treatment of obesity and metabolic dysfunction.
authors.affiliation: The Rheumatism Research Center, Catholic Research Institute of Medical Science, The Catholic University of Korea, Seoul, Republic of Korea.
authors.forename: Eun Kyung
authors.initials: EK
authors.lastname: Kim
authors.affiliation: The Rheumatism Research Center, Catholic Research Institute of Medical Science, The Catholic University of Korea, Seoul, Republic of Korea.
authors.forename: Seung Hoon
authors.initials: SH
authors.lastname: Lee
authors.affiliation: The Rheumatism Research Center, Catholic Research Institute of Medical Science, The Catholic University of Korea, Seoul, Republic of Korea.
authors.forename: Joo Yeon
authors.initials: JY
authors.lastname: Jhun
authors.affiliation: The Rheumatism Research Center, Catholic Research Institute of Medical Science, The Catholic University of Korea, Seoul, Republic of Korea.
authors.forename: Jae Kyeong
authors.initials: JK
authors.lastname: Byun
authors.affiliation: Impact Biotech, Korea 505 Banpo-Dong, Seocho-Ku, Seoul 137-040, Republic of Korea.
authors.forename: Jeong Hee
authors.initials: JH
authors.lastname: Jeong
authors.affiliation: The Rheumatism Research Center, Catholic Research Institute of Medical Science, The Catholic University of Korea, Seoul, Republic of Korea.
authors.forename: Seon-Young
authors.initials: SY
authors.lastname: Lee
authors.affiliation: The Rheumatism Research Center, Catholic Research Institute of Medical Science, The Catholic University of Korea, Seoul, Republic of Korea.
authors.forename: Jae Kyung
authors.initials: JK
authors.lastname: Kim
authors.affiliation: Division of Hepatology, Department of Internal Medicine, College of Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea, 505 Banpo-Dong, Seocho-Ku, Seoul 137-040, Republic of Korea.
authors.forename: Jong Young
authors.initials: JY
authors.lastname: Choi
authors.affiliation: The Rheumatism Research Center, Catholic Research Institute of Medical Science, The Catholic University of Korea, Seoul, Republic of Korea; Division of Rheumatology, Department of Internal Medicine, The Catholic University of Korea, Seoul 137-040, Republic of Korea.
authors.forename: Mi-La
authors.initials: ML
authors.lastname: Cho
mesh_terms: D041721:3T3-L1 Cells; D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism; D050154:Adiposity / Q000187:drug effects; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000378:metabolism; D059305:Diet, High-Fat; D004195:Disease Models, Animal; D005234:Fatty Liver / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism; D005346:Fibroblast Growth Factors / Q000235:genetics / Q000378:metabolism*; D056945:Hep G2 Cells; D006801:Humans; D020381:Interleukin-17 / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D008687:Metformin / Q000627:therapeutic use*; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000097:blood* / Q000188:drug therapy* / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000378:metabolism
chemical_list: D020381:Interleukin-17; C414620:fibroblast growth factor 21; D005346:Fibroblast Growth Factors; D008687:Metformin