title: Galectin-3 activates PPARγ and supports white adipose tissue formation and high-fat diet-induced obesity.
abstract: Galectin-3, a β-galactoside-binding lectin, is elevated in obesity and type 2 diabetes mellitus, and metformin treatment reduces these galectin-3 levels. However, the role of galectin-3 in adipogenesis remains controversial. We found that 17-month-old galectin-3-deficient (lgals3(-/-)) mice had decreased body size and epididymal white adipose tissue (eWAT) without related inflammatory diseases when fed normal chow. Galectin-3 knockdown significantly reduced adipocyte differentiation in 3T3-L1 cells and also decreased the expression of peroxisome proliferator-activated receptor (PPAR)-γ, ccaat-enhancer-binding protein α, and ccaat-enhancer-binding protein β. Endogenous galectin-3 directly interacted with PPARγ, and galectin-3 ablation reduced the nuclear accumulation and transcriptional activation of PPARγ. After a 12-week high-fat diet (60% fat), lgals3(-/-) mice had lower body weight and eWAT mass than lgals3(+/+) mice. Moreover, the expression of PPARγ and other lipogenic genes was drastically decreased in the eWAT and liver of lgals3(-/-) mice. We suggest that galectin-3 directly activates PPARγ and leads to adipocyte differentiation in vitro and in vivo. Furthermore, galectin-3 might be a potential therapeutic target in metabolic syndromes as a PPARγ regulator.
authors.affiliation: Department of Biochemistry and Molecular Biology (J.-H.B., S.-J.K., H.G.K., H.-W.L., K.-H.C.), Yonsei University College of Medicine, Seodaemun-gu, Seoul 120-752, Republic of Korea; Department of Biochemistry (H.-W.L., J.-H.K., J.S.), College of Life Science and Biotechnology, and Brain Korea 21 PLUS Project for Medical Science (J.-H.B., S.-J.K., H.G.K., K.-H.C.), Yonsei University, Seoul 120-749, Republic of Korea; and Department of Agrofood Resources (K.-A.H.), National Academy of Agricultural Science, Rural Development Administration, Suwon 441-857, Republic of Korea.
authors.forename: Jung-Hwan
authors.initials: JH
authors.lastname: Baek
authors.forename: Seok-Jun
authors.initials: SJ
authors.lastname: Kim
authors.forename: Hyeok Gu
authors.initials: HG
authors.lastname: Kang
authors.forename: Hyun-Woo
authors.initials: HW
authors.lastname: Lee
authors.forename: Jung-Hoon
authors.initials: JH
authors.lastname: Kim
authors.forename: Kyung-A
authors.initials: KA
authors.lastname: Hwang
authors.forename: Jaewhan
authors.initials: J
authors.lastname: Song
authors.forename: Kyung-Hee
authors.initials: KH
authors.lastname: Chun
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology / Q000378:metabolism; D052436:Adipose Tissue, White / Q000502:physiology*; D050154:Adiposity; D000818:Animals; D002454:Cell Differentiation; D004041:Dietary Fats / Q000008:administration & dosage / Q000009:adverse effects*; D004305:Dose-Response Relationship, Drug; D005260:Female; D037502:Galectin 3 / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000502:physiology*; D057809:HEK293 Cells; D006801:Humans; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009765:Obesity / Q000139:chemically induced* / Q000378:metabolism; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism*
chemical_list: D004041:Dietary Fats; D037502:Galectin 3; D047495:PPAR gamma