Reduced expression of Twist 1 is protective against insulin resistance of adipocytes and involves mitochondrial dysfunction.

Abstract:

:Insulin resistance (IR) has become a global epidemic that represents a serious hazard to public health. However, the precise mechanisms modulating IR have not been fully elucidated. The present study aimed to investigate the role of transcriptional factor Twist 1 in adipocyte IR and to further explore the molecular mechanism. An in vitro IR model based on cultured 3T3-L1 adipocytes was established under high glucose/insulin stimulation and an in vivo IR model in C57/BL6J mice induced by a high fat diet (HFD) was also developed. Lentivirus targeting Twist 1 silencing was introduced. The relationships between Twist 1 expression and IR state, mitochondrial dysfunction and the downstream insulin signaling pathway were assayed. Our results firstly showed the elevation of Twist 1 in IR adipocytes, and Twist 1 silencing attenuated IR. Then mitochondrial ultra-structural damage, elevated ROS, decreased MMP and ATP, and changes in mitochondrial biosynthesis-related genes in IR group indicated mitochondrial dysfunction. Further, the downstream IRS/PI3K/AKT/GluT4 pathway was showed involved in Twist 1-mediated IR. In total, we provide evidence of a protective role of Twist 1 silencing in relieving the IR state of adipocytes. Mitochondrial dysfunction and the downstream IRS/PI3K/AKT/GluT4 pathway were involved in this Twist 1-mediated IR.

journal_name

Sci Rep

journal_title

Scientific reports

authors

Lu S,Wang H,Ren R,Shi X,Zhang Y,Ma W

doi

10.1038/s41598-018-30820-z

subject

Has Abstract

pub_date

2018-08-22 00:00:00

pages

12590

issue

1

issn

2045-2322

pii

10.1038/s41598-018-30820-z

journal_volume

8

pub_type

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