4-PBA reverses autophagic dysfunction and improves insulin sensitivity in adipose tissue of obese mice via Akt/mTOR signaling.

Autor: Guo Q; Department of Respiratory, The First Affiliated Hospital of Xi'an Jiaotong University, 277 Yanta West Street, Xi'an, Shaanxi 710061, China; Critical Care Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, 277 Yanta West Street, Xi'an, Shaanxi 710061, China., Xu L; Department of Endocrinology, The Affiliated Guangren Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, China., Li H; Key Laboratory of Environment and Genes Related to Diseases, Medical School of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China., Sun H; Key Laboratory of Environment and Genes Related to Diseases, Medical School of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China., Wu S; Center for Translational Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China. Electronic address: wushufangxian@126.com., Zhou B; Department of Respiratory, The First Affiliated Hospital of Xi'an Jiaotong University, 277 Yanta West Street, Xi'an, Shaanxi 710061, China. Electronic address: zb_bob@stu.xjtu.edu.cn.
Jazyk: angličtina
Zdroj: Biochemical and biophysical research communications [Biochem Biophys Res Commun] 2017 Mar 11; Vol. 484 (3), pp. 529-535. Date of Electronic Publication: 2017 Jan 30.
DOI: 10.1016/j.bbrc.2017.01.106
Abstrakt: 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.
(Copyright © 2017 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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