Department of Dermatology, School of Medicine, University of California, Davis, Sacramento, CA 95817, USA.
Proc Natl Acad Sci U S A. 2011 Nov 15;108(46):18696-701. doi: 10.1073/pnas.1109065108. Epub 2011 Oct 3.
The breakdown of triglycerides, or lipolysis, is a tightly controlled process that regulates fat mobilization in accord with an animal's energy needs. It is well established that lipolysis is stimulated by hormones that signal energy demand and is suppressed by the antilipolytic hormone insulin. However, much still remains to be learned about regulation of lipolysis by intracellular signaling pathways in adipocytes. Here we show that galectin-12, a member of a β-galactoside-binding lectin family preferentially expressed by adipocytes, functions as an intrinsic negative regulator of lipolysis. Galectin-12 is primarily localized on lipid droplets and regulates lipolytic protein kinase A signaling by acting upstream of phosphodiesterase activity to control cAMP levels. Ablation of galectin-12 in mice results in increased adipocyte mitochondrial respiration, reduced adiposity, and ameliorated insulin resistance/glucose intolerance. This study identifies unique properties of this intracellular galectin that is localized to an organelle and performs a critical function in lipid metabolism. These findings add to the significant functions exhibited by intracellular galectins, and have important therapeutic implications for human metabolic disorders.
甘油三酯的分解，即脂解，是一个严格控制的过程，它根据动物的能量需求调节脂肪动员。脂解受信号传递能量需求的激素刺激，受抗脂解激素胰岛素抑制，这一点已经得到充分证实。然而，关于脂肪细胞内信号通路对脂解的调节，仍有许多需要了解。在这里，我们发现半乳糖凝集素-12，一种主要在脂肪细胞中表达的β-半乳糖苷结合凝集素家族的成员，作为脂解的内在负调控因子发挥作用。半乳糖凝集素-12主要定位于脂滴上，并通过作用于磷酸二酯酶活性的上游来控制 cAMP 水平，调节脂肪分解蛋白激酶 A 信号。在小鼠中敲除半乳糖凝集素-12 会导致脂肪细胞线粒体呼吸增加、脂肪量减少和胰岛素抵抗/葡萄糖不耐受改善。这项研究确定了这种定位于细胞器的细胞内半乳糖凝集素的独特特性，并在脂质代谢中发挥了关键功能。这些发现增加了细胞内半乳糖凝集素的重要功能，并对人类代谢紊乱具有重要的治疗意义。
