Mukherjee R, Kim S W, Park T, Choi M S, Yun J W
Department of Biotechnology, Daegu University, Kyungsan, Republic of Korea.
Department of Food and Nutrition, Yonsei University, Seoul, Republic of Korea.
Int J Obes (Lond). 2015 Sep;39(9):1349-58. doi: 10.1038/ijo.2015.74. Epub 2015 Apr 29.
Galectin 1 (GAL1), an animal lectin is well characterized in the context of cancer, tumor environment, but its physiological roles in obesity remain to be demonstrated. In this study, we investigated whether targeted inhibition of GAL1 prevents obesity based on the previous observations that GAL1 is highly expressed in adipose tissues of high-fat diet (HFD)-induced obese rats.
Lipogenic capacity of Lgals1 knocked down adipocytes was evaluated by determining the expression levels of major lipogenic markers using real-time PCR and immunoblot analysis. GAL1 partner proteins were identified using co-immunoprecipitation followed by protein mass fingerprinting. Finally, inhibitory effect of GAL1 by thiodigalactoside (TDG) was assessed in adipocytes and HFD-induced obese rats.
Knockdown of GAL1-encoding gene (Lgals1) attenuated adipogenesis and lipogenesis in both 3T3-L1 and HIB1B adipocytes. Further, direct treatment with TDG, a potent inhibitor of GAL1, to cultured adipocytes in vitro significantly reduced fat accumulation. Our animal experiment revealed that intraperitoneal injection of TDG (5 mg kg(-1)) once per week for 5 weeks in Sprague-Dawley (SD) rats resulted in dramatic inhibition of HFD-induced body weight gain (27.3% reduction compared with HFD-fed controls) by inhibiting adipogenesis and lipogensis as well as by increasing expression of the proteins associated with thermogenesis and energy expenditure.
GAL1 has an essential role in HFD-induced obesity development. From a clinical viewpoint, pharmaceutical targeting of GAL1 using TDG and other inhibitor compounds would be a novel therapeutic approach for the treatment of obesity.
半乳糖凝集素1（GAL1）是一种动物凝集素，在癌症、肿瘤环境方面已得到充分表征，但其在肥胖症中的生理作用仍有待证实。在本研究中，基于之前观察到GAL1在高脂饮食（HFD）诱导的肥胖大鼠脂肪组织中高表达，我们研究了靶向抑制GAL1是否能预防肥胖症。
通过实时PCR和免疫印迹分析确定主要脂肪生成标志物的表达水平，评估敲低Lgals1的脂肪细胞的脂肪生成能力。使用免疫共沉淀结合蛋白质质量指纹图谱鉴定GAL1伴侣蛋白。最后，在脂肪细胞和HFD诱导的肥胖大鼠中评估硫代二半乳糖苷（TDG）对GAL1的抑制作用。
敲低编码GAL1的基因（Lgals1）可减弱3T3-L1和HIB1B脂肪细胞的脂肪生成和脂质生成。此外，用GAL1的有效抑制剂TDG直接处理体外培养的脂肪细胞可显著减少脂肪积累。我们的动物实验表明，在Sprague-Dawley（SD）大鼠中每周腹腔注射一次TDG（5 mg kg-1），持续5周，通过抑制脂肪生成和脂质生成以及增加与产热和能量消耗相关的蛋白质表达，可显著抑制HFD诱导的体重增加（与HFD喂养的对照组相比减少27.3%）。
GAL1在HFD诱导的肥胖症发展中起重要作用。从临床角度来看，使用TDG和其他抑制剂化合物对GAL1进行药物靶向治疗将是治疗肥胖症的一种新型治疗方法。
