Effects of high fat diet on GPR109A and GPR81 gene expression
Effects of high fat diet on GPR109A and GPR81 gene expression
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DOI：
10.1016/j.bbrc.2012.07.082
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发表时间：
2012-08-24
影响因子：
3.1
通讯作者：
Judd, Robert L.
中科院分区：
文献类型：
--
作者：
Wanders, Desiree;Graff, Emily C.;Judd, Robert L.
GPR 109 A（PUMA-G，NIACR 1，HCA（2））和GPR 81（HCA（1））是主要位于脂肪细胞上的G蛋白偶联受体，介导抗脂解作用。这些细胞表面受体使脂肪细胞能够“感知”环境中的代谢变化，并通过脂解调节和释放产物（包括游离脂肪酸和促炎或抗炎脂肪因子）作出反应。GPR 109 A和GPR 81的内源性配体分别是β-羟基丁酸和乳酸，两者都是羟基羧酸和能量代谢的中间体。循环β-羟基丁酸水平在2-3天的快速和长期饥饿期间增加，而乳酸水平在剧烈运动期间升高。因此，调节这些受体的表达对于脂肪细胞的代谢传感能力和最终全身能量稳态是至关重要的。我们研究了高脂饮食诱导的肥胖对GPR 109 A和GPR 81表达的影响。将16只雄性C57 BL/6小鼠置于对照（10%kcal脂肪; n = 8）或高脂肪（60%kcal脂肪; n = 8）饮食11周。饮食诱导的肥胖显著降低了GPR 109 A和GPR 81基因在附睾脂肪垫中的表达。GPR 109 A和GPR 81基因表达的减少与脂肪组织PPAR γ基因表达的减少呈正相关。相反，用脂多糖急性处理3 T3-L1脂肪细胞和RAW 264.7巨噬细胞显著增加GPR 109 A基因表达，但对3 T3-L1脂肪细胞中的GPR 81表达没有影响。总之，慢性肥胖减少了脂肪组织中GPR 109 A和GPR 81的表达，而急性体外LPS处理增加了脂肪细胞和巨噬细胞中GPR 109 A的表达。(c)2012 Elsevier Inc. All rights reserved.
GPR109A (PUMA-G, NIACR1, HCA(2)) and GPR81 (HCA(1)) are G protein-coupled receptors located predominantly on adipocytes that mediate anti-lipolytic effects. These cell surface receptors give the adipocyte the ability to "sense" metabolic changes in the environment and respond through lipolytic regulation and release of products including free fatty acids and pro- or anti-inflammatory adipokines. The endogenous ligands for GPR109A and GPR81 are beta-hydroxybutyrate and lactate, respectively, both of which are hydroxycarboxylic acids and intermediates of energy metabolism. Circulating beta-hydroxybutyrate levels are increased during a 2-3 day fast and prolonged starvation, while lactate levels are elevated during times of intense exercise. Therefore, regulation of expression of these receptors is crucial for the metabolic sensing ability of the adipocyte and ultimately whole body energy homeostasis. We investigated the effects of high fat diet-induced obesity on expression of GPR109A and GPR81. Sixteen male C57BL/6 mice were placed on a control (10% kcal fat; n = 8) or a high fat (60% kcal fat; n = 8) diet for 11 weeks. Diet-induced obesity significantly reduced GPR109A and GPR81 gene expression in epididymal fat pads. This decrease in GPR109A and GPR81 gene expression was positively correlated with a decrease in adipose tissue PPAR gamma gene expression. In contrast, acute treatment of both 3T3-L1 adipocytes and RAW 264.7 macrophages with lipopolysaccharide significantly increased GPR109A gene expression, but had no effect on GPR81 expression in 3T3-L1 adipocytes. In conclusion, chronic obesity reduces GPR109A and GPR81 expression in the adipose tissue, while acute in vitro LPS treatment increases expression of GPR109A in adipocytes and macrophages. (c) 2012 Elsevier Inc. All rights reserved.