Galectin-3 activates PPARγ and supports white adipose tissue formation and high-fat diet-induced obesity

Endocrinology. 2015 Jan;156(1):147-56. doi: 10.1210/en.2014-1374.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3-L1 Cells
  • Adipocytes / cytology
  • Adipocytes / metabolism
  • Adipose Tissue, White / physiology*
  • Adiposity
  • Animals
  • Cell Differentiation
  • Dietary Fats / administration & dosage
  • Dietary Fats / adverse effects*
  • Dose-Response Relationship, Drug
  • Female
  • Galectin 3 / genetics
  • Galectin 3 / metabolism*
  • Gene Expression Regulation / physiology*
  • HEK293 Cells
  • Humans
  • Male
  • Mice
  • Mice, Knockout
  • Obesity / chemically induced*
  • Obesity / metabolism
  • PPAR gamma / genetics
  • PPAR gamma / metabolism*


  • Dietary Fats
  • Galectin 3
  • PPAR gamma