title: Bromodomain-containing protein 2 induces insulin resistance via the mTOR/Akt signaling pathway and an inflammatory response in adipose tissue.
abstract: Insulin resistance is a major metabolic abnormality in a large majority of patients with type II diabetes. Bromodomain-containing protein 2 (Brd2), a transcriptional co-activator/co-repressor with switch mating type/sucrose non-fermenting (SWI/SNF)-like functions that regulates chromatin, suppresses adipocyte differentiation and regulates pancreatic β-cell biology. However, the effects of Brd2 on insulin resistance remain unknown. Here, overexpression of Brd2 in white adipose tissue of wild-type (WT) mice led to insulin resistance. Brd2 overexpression induced the expression of nuclear Factor-κΒ (NF-κΒ) target genes, mainly involving proinflammatory and chemotactic factors, in adipocytes. Furthermore, it decreased the expression of DEP domain containing mTOR-interacting protein (Deptor) to enhance mechanistic target of rapamycin (mTOR) signaling, thus blocking insulin signaling. Collectively, these results provided evidence for a novel role of Brd2 in chronic inflammation and insulin resistance, suggesting its potential in improving insulin resistance and treating metabolic disorders.
authors.affiliation: The Key Laboratory of Metabolism and Molecular Medicine, The Ministry of Education, Department of Biochemistry and Molecular Biology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
authors.forename: Ruixin
authors.initials: R
authors.lastname: Sun
authors.affiliation: The Key Laboratory of Metabolism and Molecular Medicine, The Ministry of Education, Department of Biochemistry and Molecular Biology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Wu
authors.affiliation: The Key Laboratory of Metabolism and Molecular Medicine, The Ministry of Education, Department of Biochemistry and Molecular Biology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
authors.forename: Weihua
authors.initials: W
authors.lastname: Hou
authors.affiliation: The Key Laboratory of Metabolism and Molecular Medicine, The Ministry of Education, Department of Biochemistry and Molecular Biology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
authors.forename: Zujun
authors.initials: Z
authors.lastname: Sun
authors.affiliation: The Key Laboratory of Metabolism and Molecular Medicine, The Ministry of Education, Department of Biochemistry and Molecular Biology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
authors.forename: Yuxiong
authors.initials: Y
authors.lastname: Wang
authors.affiliation: The Key Laboratory of Metabolism and Molecular Medicine, The Ministry of Education, Department of Biochemistry and Molecular Biology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
authors.forename: Huanhuan
authors.initials: H
authors.lastname: Wei
authors.affiliation: The Key Laboratory of Metabolism and Molecular Medicine, The Ministry of Education, Department of Biochemistry and Molecular Biology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Mo
authors.affiliation: The Key Laboratory of Metabolism and Molecular Medicine, The Ministry of Education, Department of Biochemistry and Molecular Biology, Shanghai Medical College, Fudan University, Shanghai 200032, China. Electronic address: minyu@shmu.edu.cn.
authors.forename: Min
authors.initials: M
authors.lastname: Yu
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000378:metabolism; D052436:Adipose Tissue, White / Q000378:metabolism*; D000818:Animals; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism*; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D005947:Glucose / Q000378:metabolism; D007249:Inflammation / Q000235:genetics / Q000473:pathology*; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance / Q000235:genetics; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics; D000076222:Mechanistic Target of Rapamycin Complex 1 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D016328:NF-kappa B / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding / Q000235:genetics; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*; D014157:Transcription Factors; D014158:Transcription, Genetic; D000092468:Bromodomain Containing Proteins
chemical_list: D002868:Chromosomal Proteins, Non-Histone; D005947:Glucose; D007328:Insulin; D047908:Intracellular Signaling Peptides and Proteins; D000076222:Mechanistic Target of Rapamycin Complex 1; D016328:NF-kappa B; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; D014157:Transcription Factors; C490844:Brd2 protein, mouse; D000092468:Bromodomain Containing Proteins; C570841:deptor protein, mouse
keywords: Brd2; Inflammation; Insulin resistance; Insulin signaling pathway; mTOR signaling