期刊
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
卷 484, 期 3, 页码 529-535出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2017.01.106
关键词
Akt/mTOR signaling; Autophagy; Insulin resistance; 4-PBA
资金
- National Natural Science Foundation of China [81370899, 81472038, 81500016]
Background: 4-phenyl butyric acid (4-PBA) has been considered as a key regulator of insulin resistance in obesity. However the mechanism of 4-PBA involved in insulin resistance remains elusive. Methods: We evaluated the effect of 4-PBA on abnormal autophagy and endoplasmic reticulum (ER) stress in obese mice. 4-PBA was administered in obese mice and adipocyte models, and metabolic parameters, autophagy markers, ER stress indicators, Akt/mTOR signaling and insulin signaling molecular were assessed. Results: 4-PBA treatment not only reversed autophagic dysfunction and ER stress, but also improved impaired insulin signaling in tunicamycin-induced adipocytes, and 4-PBA also inhibited activated ER stress and elevated insulin sensitivity in adipocytes with Atg7 siRNA. Additionally, administration of 4-PBA improves glucose tolerance and insulin sensitivity in obese mice via regulating abnormal autophagy and ER stress in adipose tissue. The protective effects of 4-PBA were nullified by suppression of Akt and mTOR in adipocytes, suggesting that 4-PBA inhibits autophagy and restores insulin sensitivity via Akt/mTOR signaling partially. Conclusions: 4-PBA reverses autophagic dysfunction and improves insulin sensitivity in adipose tissue of obese mice via Akt/mTOR signaling partly, which could be regarded as novel opportunities for treatment of insulin resistance. (C) 2017 Elsevier Inc. All rights reserved.
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