Galectin-1 accelerates high-fat diet-induced obesity by activation of peroxisome proliferator-activated receptor gamma (PPARγ) in mice

Galectin-1 contains a carbohydrate-recognition domain (CRD) as a member of the lectin family. Here, we investigated whether galectin-1 regulates adipogenesis and lipid accumulation. Galectin-1 mRNA is highly expressed in metabolic tissues such as the muscle and adipose tissues. Higher mRNA expression of galectin-1 was detected in white adipose tissues (WATs) of mice that were fed a high-fat diet (HFD) than in those of mice fed a normal-fat diet (NFD). Protein expression of galectin-1 also increased during adipocyte differentiation. Galectin-1 silencing inhibited the differentiation of 3T3-L1 cells and the expression of lipogenic factors, such as PPAR gamma, C/EBP alpha, FABP4, and FASN at both mRNA and protein levels. Lactose, an inhibitor by the binding with CRD of galectin-1 in extracellular matrix, did not affect adipocyte differentiation. Galectin-1 is localized in multiple cellular compartments in 3T3-L1 cells. However, we found that DMI (dexamethasone, methylisobutylxanthine, insulin) treatment increased its nuclear localization. Interestingly, galectin-1 interacted with PPAR gamma. Galectin-1 overexpression resulted in increased PPAR gamma expression and transcriptional activity. Furthermore, we prepared galectin-1-knockout (Lgals1(-/-)) mice and fed a 60% HFD. After 10 weeks, Lgals1(-/-) mice exhibited lower body weight and gonadal WAT (gWAT) mass than wild-type mice. Fasting glucose level was also lower in Lgals1(-/-)mice than that in wild-type mice. Moreover, lipogenic genes were significantly downregulated in the gWATs and liver tissues from Lgals1(-/-) mice. Pro-inflammatory cytokines, such as CCL2, CCL3, TNF alpha, and F4/80, as well as macrophage markers, were also drastically downregulated in the gWATs and liver tissues of Lgals1(-/-) mice. In addition, Lgals1(-/-)mice showed elevated expression of genes involved in thermogenesis in the brown adipose tissue. Collectively, galectin-1 exacerbates obesity of mice fed HFD by increment of PPAR gamma expression and activation. Our findings suggest that galectin-1 could be a potential therapeutic target for obesity and needed further study for clinical application.

Automated summary

Galectin-1 plays a crucial role in adipogenesis and lipid accumulation by increasing PPAR gamma expression and activation, exacerbating obesity in mice fed a high-fat diet. Knockout of Galectin-1 gene can reduce body weight and adipose tissue mass, lower fasting glucose levels, and downregulate lipogenic genes.