| 作者: |
Xuefei Gao, Kuai Li, Xiaoyan Hui, Xiangping Kong, Gary Sweeney, Yu Wang, Aimin Xu, Maikun Teng, Pentao Liu, Donghai Wu |
| 摘要: |
The adipocyte is the principal cell type for fat storage. CPT1 (carnitinepalmitoyltransferase-1) is the rate-limiting enzyme forfattyacidbeta-oxidation, but the physiological roleofCPT
1 in
adipocytesremains unclear. In the present study, we focused on the specific roleofCPT
1A
in the normal functioningofadipocytes. Three 3T3-L1 adipocyte cell lines stably expressing hCPT
1A
(human CPT
1A
) cDNA, mouse CPT
1A
shRNA (short-hairpin RNA) or GFP (green fluorescent protein) were generated and the biological functionsofthese cell lines were characterized. Alteration in CPT1 activity, either by ectopic overexpression or pharmacological inhibition using etomoxir, did not affect adipocyte differentiation. However, overexpressionofhCPT I A significantly reduced the contentofintracellular NEFAs (non-esterifiedfattyacids) compared with the control cells whenadipocyteswere challenged withfattyacids. The changes were accompanied by an increase infattyaciduptake and a decrease infattyacidrelease. Interestingly, CPT
1A
protected againstfattyacid-inducedinsulin resistance and expressionofpro-inflammatory adipokines such as TNF-alpha (tumour necrosis factor-alpha) and IL-6 (interleukin-6) inadipocytes. Further studies demonstrated that JNK (c-JunNterminalkinase) activity Was substantially suppressed upon CPT
1A
overexpression, whereas knockdown or pharmacological inhibitionofCPT1 caused a significant enhancementofJNK activity. The specific inhibitorofJNK SP600125 largely abolished the changes caused by the shRNA- and etomoxir-mediated decrease in CPT1 activity. Moreover, C
2C
12 myocytes co-cultured withadipocytespre-treated withfattyacids displayed altered insulin sensitivity. Taken together, our findings have identified a favourable role for CPT
1A
inadipocytesto attenuatefattyacid-evoked insulin resistance and inflammation viasuppressionofJNK.
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