Endoplasmic reticulum stress-mediated high-fat diet, palmitic acid-induced insulin resistance in skeletal muscle and interventional effects of fenofibrate
10.3969/j.issn.1001-1978.2014.11.016
- VernacularTitle:内质网应激介导高脂及棕榈酸致骨骼肌胰岛素抵抗及非诺贝特的干预机制初探
- Author:
Yingying BAO
;
Yunxia LU
;
Guanjun CHEN
;
Jingjing CHENG
;
Qiu ZHANG
- Publication Type:Journal Article
- Keywords:
endoplasmic reticulum stress;
skeletal muscle;
high-fat diet;
palmitic acid;
fenofibrate;
insu-lin resistance
- From:
Chinese Pharmacological Bulletin
2014;(11):1557-1563
- CountryChina
- Language:Chinese
-
Abstract:
Aim To investigate endoplasmic reticulum stress ( ERS)-mediated high-fat diet and palmitic acid-induced insulin resistance ( IR) in skeletal muscle and interventional effects of fenofibrate both in vivo and in vitro tests. Methods Female SD rats were randomly subjected to a standard control diet ( SCD) or high-fat diet ( HFD) for 20 weeks, then the HFD group was di-vided into high-fat-diet group and high-fat-diet group treated with fenofibrate ( HFD +FF, 30 mg · kg-1 · d-1 ) for another 8 weeks. The changes of IR and ex-pression of peroxisome proliferator-activated receptor α( PPARα) , glucose regulated protein 78 ( GRP78 ) and transcription factors GADD153 ( CHOP ) were as-sessed respectively. C2C12 myotubes were divided into normal control group ( NC ) , model group ( palmitic acid, PA) , postive control drug group ( tunicamycin, TM) and treatment group ( fenofibric acid, FA+PA) , the expressions of GRP78 and CHOP were assessed re-spectively. Insulin-stimulated phosphorylation of Akt was also analyzed to detect changes of insulin sensitivi-ty in C2 C12 . Results The high-fat diet induced obvi-ous IR and upregulated ERS markers GRP78 and CHOP in skeletal muscle of rats, and these responses were attenuated by treatment with fenofibrate. Incuba-tion of myotubes with palmitic acid or tunicamycin sig-nificantly increased expression of ERS markers GRP78 and CHOP. Meanwhile, insulin-stimulated phosphoryl-ation of Akt was inhibited obviously. Pre-incubation with FA markedly inverted PA-induced ERS and insu-lin-stimulated phosphorylation of Akt. Conclusion Fenofibrate ( fenofibric acid) has obvious effects of IR on skeletal muscle tissues and cells, which may be re-lated with reduced expression of GRP78 and CHOP in ERS.
