Energy intake and adiponectin gene expression

Energy intake and adiponectin gene expression. Am J Physiol Endocrinol Metab 300: E809-E816, 2011. First published February 15, 2011; doi: 10.1152/ajpendo.00004.2011.-Hypoadiponectinemia and decreased adiponectin gene expression in white adipose tissue (WAT) have been well observed in obese subjects and animal models. However, the mechanism for obesity-associated hypoadiponectinemia is still largely unknown. To investigate the regulatory role of energy intake, dietary fat, and adiposity in adiponectin gene expression and blood adiponectin level, a series of feeding regimens was employed to manipulate energy intake and dietary fat in obese-prone C57BL/6, genetically obese ob/ob, obese-resistant A/J and peroxisome proliferator-activated receptor-alpha gene knockout (PPAR alpha KO) mice. Adiponectin gene expression in WAT and circulating adiponectin levels were studied in these dietary intervention-treated mice. Our study showed that calorie restriction (CR) robustly increased adiponectin gene expression in epididymal fat and blood adiponectin levels in both low-fat (LF) and high-fat (HF) diet-fed C57BL/6 mice. Although HF pair-fed C57BL/6 mice received the same amount of calories as LF ad libitum-fed mice, HF diet clearly increased adiposity but showed no significant effects on adiponectin gene expression and blood adiponectin level. CR also significantly increased blood adiponectin levels in ob/ob and A/J mice. Neither CR nor HF feeding displayed any significant effect on blood adiponectin half-life in C57BL/6 mice. Interestingly, CR increased PPAR alpha expression in epididymal fat of C57BL/6 mice. Low levels of blood adiponectin and adiponectin gene expression in WAT were observed in PPAR alpha KO mice. PPAR alpha agonist treatment increased adiponectin mRNA levels in 3T3-L1 adipocytes. Furthermore, CR failed to increase adiponectin gene expression and blood adiponectin levels in PPAR alpha KO mice. Therefore, our study demonstrated that energy intake, not dietary fat, plays an important role in regulating adiponectin gene expression and blood adiponectin level. PPAR alpha mediates CR-enhanced adiponectin gene expression in WAT.