Abstract 12703: Regulation of an Insulin-sensitizing and Anti-inflammatory Adipokine Adipolin/ctrp12 By Kruppel-like Factor 15
Background: Obese states characterized by chronic inflammation are closely linked with the development of metabolic dysfunction and cardiovascular disorders. Previously, we have demonstrated that adipolin/CTRP12 functions as an anti-inflammatory adipokine that improves insulin sensitivity. Although obese conditions downregulate adipolin, its molecular mechanism has not been fully clarified. Here we investigated the mechanism of adipolin regulation by the inflammatory state in obesity.
Results: and methods Adipolin mRNA expression was reduced in fat tissue in diet-induced obese (DIO) mice compared with control mice. DIO mice showed a decrease in adipose expression of Kruppel-like factor (KLF) 9 and KLF15 among several KLFs that are substantially present in adipocytes. In cultured 3T3L1 adipocytes, treatment with an inflammatory stimulus TNFα significantly reduced the mRNA expression of adipolin, KLF9 and KLF15. Pretreatment of 3T3L1 adipocytes with the JNK inhibitor SP600125 blocked the inhibitory effects of TNFα on adipolin, KLF9 and KLF15 expression. In contrast, treatment with the p38 MAPK inhibitor SB203580 had no effects on TNFα-induced downregulation of adipolin, KLF9 and KLF15. Overexpression of KLF15 but not KLF9 enhanced the promoter activity of adipolin in HEK293 cells as determined by luciferase promoter assay. Furthermore, adenovirus-mediated overexpression of KLF15 rescued TNFα-induced reduction of adipolin expression in adipocytes.
Conclusions: Our data document that adipose inflammation suppresses the transcriptional activation of adipolin gene via JNK-dependent downregulation of KLF15 in adipocytes. Thus, strategies to enhance adipolin production via modulation of KLF15 may be useful for the treatment of metabolic dysfunction in obesity.
- © 2013 by American Heart Association, Inc.