Repression of Adipose Tissue Fibrosis through a PRDM16-GTF2IRD1 Complex Improves Systemic Glucose Homeostasis. Academic Article uri icon

Overview

abstract

  • Adipose tissue fibrosis is a hallmark of malfunction that is linked to insulin resistance and type 2 diabetes; however, what regulates this process remains unclear. Here we show that the PRDM16 transcriptional complex, a dominant activator of brown/beige adipocyte development, potently represses adipose tissue fibrosis in an uncoupling protein 1 (UCP1)-independent manner. By purifying the PRDM16 complex, we identified GTF2IRD1, a member of the TFII-I family of DNA-binding proteins, as a cold-inducible transcription factor that mediates the repressive action of the PRDM16 complex on fibrosis. Adipocyte-selective expression of GTF2IRD1 represses adipose tissue fibrosis and improves systemic glucose homeostasis independent of body-weight loss, while deleting GTF2IRD1 promotes fibrosis in a cell-autonomous manner. GTF2IRD1 represses the transcription of transforming growth factor β-dependent pro-fibrosis genes by recruiting PRDM16 and EHMT1 onto their promoter/enhancer regions. These results suggest a mechanism by which repression of obesity-associated adipose tissue fibrosis through the PRDM16 complex leads to an improvement in systemic glucose homeostasis.

publication date

  • January 9, 2018

Research

keywords

  • Adipose Tissue
  • DNA-Binding Proteins
  • Glucose
  • Homeostasis
  • Muscle Proteins
  • Nuclear Proteins
  • Trans-Activators
  • Transcription Factors

Identity

PubMed Central ID

  • PMC5765755

Scopus Document Identifier

  • 85044737167

Digital Object Identifier (DOI)

  • 10.1016/j.cmet.2017.12.005

PubMed ID

  • 29320702

Additional Document Info

volume

  • 27

issue

  • 1