Effects of high fat diet on GPR109A and GPR81 gene expression

• Published in: Biochemical and biophysical research communications Vol. 425; no. 2; pp. 278 - 283
• Main Authors: Wanders, Desiree, Graff, Emily C., Judd, Robert L.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 24-08-2012
• Subjects: 3T3-L1 Cells; Adipocytes - metabolism; Adipose Tissue - metabolism; Animals; Cell Line; Diet, High-Fat - adverse effects; G protein-coupled receptor; Gene Expression Regulation; HCA1; HCA2; Inflammation; Inflammation - genetics; Inflammation - metabolism; Lipopolysaccharides; Macrophages - metabolism; Male; Mice; Mice, Inbred C57BL; Obesity; Obesity - genetics; Obesity - metabolism; PPAR gamma - genetics; PUMA-G; Receptors, G-Protein-Coupled - genetics; Receptors, Nicotinic - genetics; G protein-coupled receptor; Obesity; HCA1; Inflammation; HCA2; PUMA-G
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2012.07.082

► High fat diet reduces adipose tissue gene expression of GPR109A and GPR81. ► GPR109A and GPR81 are positively correlated with PPARγ gene expression in fat. ► Lipopolysaccharide treatment increases GPR109A expression in 3T3-L1 adipocytes. ► Lipopolysaccharide treatment increases GPR109A expression in RAW 264.7 macrophages. ► Lipopolysaccharide treatment does not effect GPR81 expression in 3T3-L1 adipocytes.
GPR109A (PUMA-G, NIACR1, HCA2) and GPR81 (HCA1) 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 β-hydroxybutyrate and lactate, respectively, both of which are hydroxycarboxylic acids and intermediates of energy metabolism. Circulating β-hydroxybutyrate levels are increased during a 2–3day 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 11weeks. 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 PPARγ 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.