title: BMP4-mediated brown fat-like changes in white adipose tissue alter glucose and energy homeostasis.
abstract: Expression of bone morphogenetic protein 4 (BMP4) in adipocytes of white adipose tissue (WAT) produces "white adipocytes" with characteristics of brown fat and leads to a reduction of adiposity and its metabolic complications. Although BMP4 is known to induce commitment of pluripotent stem cells to the adipocyte lineage by producing cells that possess the characteristics of preadipocytes, its effects on the mature white adipocyte phenotype and function were unknown. Forced expression of a BMP4 transgene in white adipocytes of mice gives rise to reduced WAT mass and white adipocyte size along with an increased number of a white adipocyte cell types with brown adipocyte characteristics comparable to those of beige or brite adipocytes. These changes correlate closely with increased energy expenditure, improved insulin sensitivity, and protection against diet-induced obesity and diabetes. Conversely, BMP4-deficient mice exhibit enlarged white adipocyte morphology and impaired insulin sensitivity. We identify peroxisome proliferator-activated receptor gamma coactivator 1-α (PGC1α) as the target of BMP signaling required for these brown fat-like changes in WAT. This effect of BMP4 on WAT appears to extend to human adipose tissue, because the level of expression of BMP4 in WAT correlates inversely with body mass index. These findings provide a genetic and metabolic basis for BMP4's role in altering insulin sensitivity by affecting WAT development.
authors: Key Laboratory of Molecular Medicine, the Ministry of Education, Department of Biochemistry and Molecular Biology,  Fudan University Shanghai Medical College, Shanghai 200032, People's Republic of  China.
authors: Shu-Wen
authors: SW
authors: Qian
authors: Yan
authors: Y
authors: Tang
authors: Xi
authors: X
authors: Li
authors: Yuan
authors: Y
authors: Liu
authors: You-You
authors: YY
authors: Zhang
authors: Hai-Yan
authors: HY
authors: Huang
authors: Rui-Dan
authors: RD
authors: Xue
authors: Hao-Yong
authors: HY
authors: Yu
authors: Liang
authors: L
authors: Guo
authors: Hui-Di
authors: HD
authors: Gao
authors: Yan
authors: Y
authors: Liu
authors: Xia
authors: X
authors: Sun
authors: Yi-Ming
authors: YM
authors: Li
authors: Wei-Ping
authors: WP
authors: Jia
authors: Qi-Qun
authors: QQ
authors: Tang
mesh_terms: D041721:3T3-L1 Cells; D051698:Activating Transcription Factor 2 / Q000378:metabolism; D052437:Adipocytes, Brown / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D052438:Adipocytes, White / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D002001:Adipose Tissue, Brown / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure; D052436:Adipose Tissue, White / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism* / Q000648:ultrastructure; D000818:Animals; D055415:Bone Morphogenetic Protein 4 / Q000235:genetics* / Q000378:metabolism*; D059305:Diet, High-Fat; D004734:Energy Metabolism / Q000187:drug effects; D050556:Fatty Acid-Binding Proteins / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D005947:Glucose / Q000378:metabolism*; D006706:Homeostasis / Q000187:drug effects; D006801:Humans; D007328:Insulin / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008928:Mitochondria / Q000378:metabolism / Q000648:ultrastructure; D009929:Organ Size / Q000187:drug effects; D010101:Oxygen Consumption / Q000187:drug effects; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D010641:Phenotype; D013851:Thinness / Q000378:metabolism / Q000473:pathology; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D051698:Activating Transcription Factor 2; C497106:Atf2 protein, mouse; D055415:Bone Morphogenetic Protein 4; C493411:Fabp4 protein, mouse; D050556:Fatty Acid-Binding Proteins; D007328:Insulin; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C485290:Ppargc1a protein, mouse; D015534:Trans-Activators; D014157:Transcription Factors; D048051:p38 Mitogen-Activated Protein Kinases; D005947:Glucose
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