The role of autophagy in high-fat diet-induced insulin resistance of adipose tissues in mice

PeerJ

article

Yovita Permata Budi¹  Yi-Hsuan Li³  Chien Huang³  Mu-En Wang⁴  Yi-Chun Lin⁵  De-Shien Jong³  Chih-Hsien Chiu³  Yi-Fan Jiang¹ 

[1] Graduate Institute of Molecular and Comparative Pathobiology, National Taiwan University;School of Veterinary Medicine, National Taiwan University;Department of Animal Science and Technology, National Taiwan University;Department of Pathology, Duke University;Department of Animal Science, National Chung Hsing University

关键词: Obesity;    High-fat diet;    Autophagy;    Insulin resistance;    ER stress;    Apoptosis;   

DOI  :  10.7717/peerj.13867

学科分类：社会科学、人文和艺术（综合）

来源: Inra

【 摘 要 】

AimsStudies have observed changes in autophagic flux in the adipose tissue of type 2 diabetes patients with obesity. However, the role of autophagy in obesity-induced insulin resistance is unclear. We propose to confirm the effect of a high-fat diet (HFD) on autophagy and insulin signaling transduction from adipose tissue to clarify whether altered autophagy-mediated HFD induces insulin resistance, and to elucidate the possible mechanisms in autophagy-regulated adipose insulin sensitivity.MethodsEight-week-old male C57BL/6 mice were fed with HFD to confirm the effect of HFD on autophagy and insulin signaling transduction from adipose tissue. Differentiated 3T3-L1 adipocytes were treated with 1.2 mM fatty acids (FAs) and 50 nM Bafilomycin A1 to determine the autophagic flux. 2.5 mg/kg body weight dose of Chloroquine (CQ) in PBS was locally injected into mouse epididymal adipose (10 and 24 h) and 40 µM of CQ to 3T3-L1 adipocytes for 24 h to evaluate the role of autophagy in insulin signaling transduction.ResultsThe HFD treatment resulted in a significant increase in SQSTM1/p62, Rubicon expression, and C/EBP homologous protein (CHOP) expression, yet the insulin capability to induce Akt (Ser473) and GSK3β (Ser9) phosphorylation were reduced. PHLPP1 and PTEN remain unchanged after CQ injection. In differentiated 3T3-L1 adipocytes treated with CQ, although the amount of phospho-Akt stimulated by insulin in the CQ-treated group was significantly lower, CHOP expressions and cleaved caspase-3 were increased and bafilomycin A1 induced less accumulation of LC3-II protein.ConclusionLong-term high-fat diet promotes insulin resistance, late-stage autophagy inhibition, ER stress, and apoptosis in adipose tissue. Autophagy suppression may not affect insulin signaling transduction via phosphatase expression but indirectly causes insulin resistance through ER stress or apoptosis.

【 授权许可】

CC BY