title: Id1 Promotes Obesity by Suppressing Brown Adipose Thermogenesis and White Adipose Browning.
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 ofUcp1Inhibitor 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 ofId1causes age-associated and high-fat diet-induced obesity in mice. Id1 suppresses BAT thermogenesis by binding to and suppressing PGC1α 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 inId1-deficient mouse embryonic fibroblasts. At the molecular level, Id1 directly interacts with and suppresses Ebf2 transcriptional activity, leading to reduced expression ofPrdm16, 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.
authors.affiliation: Department of Biochemistry and Molecular Biology, Molecular Oncology and Biomarkers Program, Georgia Cancer Center, Augusta University, Augusta, GA.
authors.forename: Mallikarjun
authors.initials: M
authors.lastname: Patil
authors.affiliation: Department of Biochemistry and Molecular Biology, Molecular Oncology and Biomarkers Program, Georgia Cancer Center, Augusta University, Augusta, GA.
authors.forename: Bal Krishan
authors.initials: BK
authors.lastname: Sharma
authors.affiliation: Department of Biochemistry and Molecular Biology, Molecular Oncology and Biomarkers Program, Georgia Cancer Center, Augusta University, Augusta, GA.
authors.forename: Sawsan
authors.initials: S
authors.lastname: Elattar
authors.affiliation: Department of Biochemistry and Molecular Biology, Molecular Oncology and Biomarkers Program, Georgia Cancer Center, Augusta University, Augusta, GA.
authors.forename: Judith
authors.initials: J
authors.lastname: Chang
authors.affiliation: Department of Biochemistry and Molecular Biology, Molecular Oncology and Biomarkers Program, Georgia Cancer Center, Augusta University, Augusta, GA.
authors.forename: Shweta
authors.initials: S
authors.lastname: Kapil
authors.affiliation: Department of Biochemistry and Molecular Biology, Molecular Oncology and Biomarkers Program, Georgia Cancer Center, Augusta University, Augusta, GA.
authors.forename: Jinling
authors.initials: J
authors.lastname: Yuan
authors.affiliation: Department of Biochemistry and Molecular Biology, Molecular Oncology and Biomarkers Program, Georgia Cancer Center, Augusta University, Augusta, GA sande@augusta.edu.
authors.forename: Ande
authors.initials: A
authors.lastname: Satyanarayana
mesh_terms: D000069797:Adipocytes, Beige / Q000378:metabolism*; D002001:Adipose Tissue, Brown / Q000378:metabolism*; D052436:Adipose Tissue, White / Q000378:metabolism*; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics; D003080:Cold Temperature; D004268:DNA-Binding Proteins / Q000235:genetics; D059305:Diet, High-Fat; D005786:Gene Expression Regulation; D051798:Inhibitor of Differentiation Protein 1 / Q000235:genetics*; D051379:Mice; D008822:Mice, Transgenic; D009765:Obesity / Q000235:genetics*; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D022722:Thermogenesis / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics; D000071256:Uncoupling Protein 1 / Q000235:genetics
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D004268:DNA-Binding Proteins; D051798:Inhibitor of Differentiation Protein 1; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D014157:Transcription Factors; D000071256:Uncoupling Protein 1; C489922:Ebf2 protein, mouse; C497455:Idb1 protein, mouse; C485290:Ppargc1a protein, mouse; C521133:Prdm16 protein, mouse; C000604372:Ucp1 protein, mouse