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 PPARγ, C/EBPα, 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 PPARγ. Galectin-1 overexpression resulted in increased PPARγ 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, TNFα, 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 PPARγ expression and activation. Our findings suggest that galectin-1 could be a potential therapeutic target for obesity and needed further study for clinical application.

Galectin-1 包含碳水化合物识别域 (CRD) 作为凝集素家族的成员。在这里，我们研究了 galectin-1 是否调节脂肪生成和脂质积累。Galectin-1 mRNA 在代谢组织如肌肉和脂肪组织中高度表达。在喂食高脂肪饮食 (HFD) 的小鼠的白色脂肪组织 (WAT) 中检测到的 galectin-1 mRNA 表达高于喂食正常脂肪饮食 (NFD) 的小鼠。在脂肪细胞分化过程中，galectin-1 的蛋白质表达也增加。Galectin-1 沉默抑制 3T3-L1 细胞的分化和脂肪生成因子的表达，如 PPARγ、C/EBPα、FABP4 和 FASN 在 mRNA 和蛋白质水平。乳糖是一种通过与细胞外基质中半乳糖凝集素-1 的 CRD 结合的抑制剂，不影响脂肪细胞分化。Galectin-1 位于 3T3-L1 细胞的多个细胞区室中。然而，我们发现 DMI（地塞米松、甲基异丁基黄嘌呤、胰岛素）处理增加了其核定位。有趣的是，galectin-1 与 PPARγ 相互作用。Galectin-1 过表达导致 PPARγ 表达和转录活性增加。此外，我们准备了半乳糖凝集素-1-敲除（Lgals1 ^{- / -} ) 小鼠并喂食 60% HFD。10 周后，Lgals1 ^-/-小鼠的体重和性腺 WAT (gWAT) 质量低于野生型小鼠。Lgals1 ^-/-小鼠的空腹血糖水平也低于野生型小鼠。此外，来自Lgals1 ^-/-小鼠的 gWAT 和肝组织中的脂肪生成基因显着下调。促炎细胞因子，例如 CCL2、CCL3、TNFα 和 F4/80，以及巨噬细胞标志物，在Lgals1 ^-/-小鼠的 gWAT 和肝组织中也显着下调。此外，Lgals 1 ^-/-小鼠的棕色脂肪组织中与产热相关的基因表达升高。总的来说，galectin-1 通过增加 PPARγ 表达和激活加剧了喂食 HFD 的小鼠的肥胖。我们的研究结果表明，galectin-1 可能是肥胖症的潜在治疗靶点，需要进一步研究以进行临床应用。