Galectin-3 Activates PPARγ and Supports White Adipose Tissue Formation and High-Fat Diet-Induced Obesity

Galectin-3, a beta-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)-gamma, ccaat-enhancer-binding protein alpha, and ccaat-enhancer-binding protein beta. Endogenous galectin-3 directly interacted with PPAR gamma, and galectin-3 ablation reduced the nuclear accumulation and transcriptional activation of PPAR gamma. 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 PPAR gamma and other lipogenic genes was drastically decreased in the eWAT and liver of lgals3(-/-) mice. We suggest that galectin-3 directly activates PPAR gamma and leads to adipocyte differentiation in vitro and in vivo. Furthermore, galectin-3 might be a potential therapeutic target in metabolic syndromes as a PPAR gamma regulator.