Id1 promotes obesity by suppressing brown adipose thermogenesis and white adipose browning

Mallikarjun Patil, Bal Krishan Sharma, Sawsan Elattar, Judith Chang, Shweta Kapil, Jinling Yuan, Ande Satyanarayana

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Obesity results from increased energy intake or defects in energy expenditure. Brown adipose tissue (BAT) is specialized for energy expenditure, a process called adaptive thermogenesis. Peroxisome proliferator-activated receptor γ coactivator 1α (PGC1α) controls BAT-mediated thermogenesis by regulating the expression of Ucp1. Inhibitor of differentiation 1 (Id1) is a helix-loop-helix transcription factor that plays an important role in cell proliferation and differentiation. We demonstrate a novel function of Id1 in BAT thermogenesis and programming of beige adipocytes in white adipose tissue (WAT). We found that adipose tissue-specific overexpression of Id1 causes age-associated and high-fat diet-induced obesity in mice. Id1 suppresses BAT thermogenesis by binding to and suppressing PGC1a transcriptional activity. In WAT, Id1 is mainly localized in the stromal vascular fraction, where the adipose progenitor/precursors reside. Lack of Id1 increases beige gene and Ucp1 expression in the WAT in response to cold exposure. Furthermore, brown-like differentiation is increased in Id1-deficient mouse embryonic fibroblasts. At the molecular level, Id1 directly interacts with and suppresses Ebf2 transcriptional activity, leading to reduced expression of Prdm16, which determines beige/brown adipocyte cell fate. Overall, the study highlights the existence of novel regulatory mechanisms between Id1/PGC1α and Id1/Ebf2 in controlling brown fat metabolism, which has significant implications in the treatment of obesity and its associated diseases, such as diabetes.

Original languageEnglish (US)
Pages (from-to)1611-1625
Number of pages15
JournalDiabetes
Volume66
Issue number6
DOIs
StatePublished - Jun 1 2017

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Brown Adipose Tissue
Thermogenesis
Obesity
White Adipose Tissue
Energy Metabolism
Brown Adipocytes
Peroxisome Proliferator-Activated Receptors
High Fat Diet
Energy Intake
Blood Vessels
Adipose Tissue
Cell Differentiation
Transcription Factors
Fibroblasts
Cell Proliferation
Gene Expression

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Id1 promotes obesity by suppressing brown adipose thermogenesis and white adipose browning. / Patil, Mallikarjun; Sharma, Bal Krishan; Elattar, Sawsan; Chang, Judith; Kapil, Shweta; Yuan, Jinling; Satyanarayana, Ande.

In: Diabetes, Vol. 66, No. 6, 01.06.2017, p. 1611-1625.

Research output: Contribution to journalArticle

Patil, M, Sharma, BK, Elattar, S, Chang, J, Kapil, S, Yuan, J & Satyanarayana, A 2017, 'Id1 promotes obesity by suppressing brown adipose thermogenesis and white adipose browning', Diabetes, vol. 66, no. 6, pp. 1611-1625. https://doi.org/10.2337/db16-1079
Patil M, Sharma BK, Elattar S, Chang J, Kapil S, Yuan J et al. Id1 promotes obesity by suppressing brown adipose thermogenesis and white adipose browning. Diabetes. 2017 Jun 1;66(6):1611-1625. https://doi.org/10.2337/db16-1079
Patil, Mallikarjun ; Sharma, Bal Krishan ; Elattar, Sawsan ; Chang, Judith ; Kapil, Shweta ; Yuan, Jinling ; Satyanarayana, Ande. / Id1 promotes obesity by suppressing brown adipose thermogenesis and white adipose browning. In: Diabetes. 2017 ; Vol. 66, No. 6. pp. 1611-1625.
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