Transcriptional Regulation of an Insulin-Sensitizing Adipokine Adipolin/CTRP12 in Adipocytes by Krüppel-Like Factor 15
Open Access
- 16 December 2013
- journal article
- research article
- Published by Public Library of Science (PLoS) in PLOS ONE
- Vol. 8 (12), e83183
- https://doi.org/10.1371/journal.pone.0083183
Abstract
Obese states characterized by chronic inflammation are closely linked to the development of metabolic dysfunction. We identified adipolin/CTRP12 as an insulin-sensitizing and anti-inflammatory adipokine. Although obese conditions down-regulate adipolin expression, its molecular mechanism is largely unknown. Here we show that the transcriptional regulator Krüppel-like factor (KLF) 15 is involved in the regulation of adipolin expression in adipocytes. White adipose tissue from diet-induced obese (DIO) mice showed decreased expression of KLF9 and KLF15 among several KLFs, which was accompanied by reduced expression of adipolin. In cultured 3T3L1 adipocytes, treatment with TNFα significantly reduced the mRNA levels of KLF9, KLF15 and adipolin. Adenovirus-mediated overexpression of KLF15 but not KLF9 reversed TNFα-induced reduction of adipolin expression in adipocytes. Conversely, gene targeting ablation of KLF15 attenuated adipolin expression in adipocytes. Expression of KLF15 but not KLF9 enhanced the promoter activity of adipolin in HEK293 cells. Pretreatment of 3T3L1 adipocytes with the JNK inhibitor SP600125, but not p38 MAPK inhibitor SB203580 blocked the inhibitory effects of TNFα on adipolin and KLF15 expression. These data suggest that adipose inflammation under conditions of obesity suppresses adipolin expression via JNK-dependent down-regulation of KLF15 in adipocytes.Keywords
This publication has 44 references indexed in Scilit:
- Adipolin/C1qdc2/CTRP12 Protein Functions as an Adipokine That Improves Glucose MetabolismPublished by Elsevier BV ,2011
- Overexpression of KLF15 Transcription Factor in Adipocytes of Mice Results in Down-regulation of SCD1 Protein Expression in Adipocytes and Consequent Enhancement of Glucose-induced Insulin SecretionPublished by Elsevier BV ,2011
- Metabolic Regulation by C1q/TNF-related Protein-13 (CTRP13)Published by Elsevier BV ,2011
- Macrophages in the Pathogenesis of AtherosclerosisCell, 2011
- Adipokines in inflammation and metabolic diseaseNature Reviews Immunology, 2011
- Krüppel-like factor KLF9 regulates PPARγ transactivation at the middle stage of adipogenesisCell Death & Differentiation, 2010
- Adiponectin Promotes Macrophage Polarization toward an Anti-inflammatory PhenotypeJournal of Biological Chemistry, 2010
- Regulation of Gluconeogenesis by Krüppel-like Factor 15Cell Metabolism, 2007
- Abdominal obesity and metabolic syndromeNature, 2006
- Role of Krüppel-like Factor 15 (KLF15) in Transcriptional Regulation of AdipogenesisJournal of Biological Chemistry, 2005