title: BMP4 Cross-talks With Estrogen/ERα Signaling to Regulate Adiposity and Glucose Metabolism in Females.
abstract: Similar to estrogens, bone morphogenetic protein 4 (BMP4) promotes the accumulation of more metabolically active subcutaneous fat and reduction of visceral fat. However, whether there is a cross-talk between BMP4 and estrogen signaling remained unknown. Herein, we found that BMP4 deficiency in white adipose tissue (WAT) increased the estrogen receptor α (ERα) level and its signaling, which prevented adult female mice from developing high fat diet (HFD)-induced obesity and insulin resistance; estrogens depletion up regulated BMP4 expression to overcome overt adiposity and impaired insulin sensitivity with aging, and failure of BMP4 regulation due to genetic knockout led to more fat gain in aged female mice. This mutual regulation between BMP4 and estrogen/ERα signaling may also happen in adipose tissue of women, since the BMP4 level significantly increased after menopause, and was inversely correlated with body mass index (BMI). These findings suggest a counterbalance between BMP4 and estrogen/ERα signaling in the regulation of adiposity and relative metabolism in females.
authors: Key Laboratory of Metabolism and Molecular Medicine, The Ministry of Education, Department of Biochemistry and Molecular Biology, Fudan University Shanghai Medical College, Shanghai 200032, PR China.
authors: Shu-Wen
authors: SW
authors: Qian
authors: Key Laboratory of Metabolism and Molecular Medicine, The Ministry of Education, Department of Biochemistry and Molecular Biology, Fudan University Shanghai Medical College, Shanghai 200032, PR China.
authors: Yan
authors: Y
authors: Liu
authors: Key Laboratory of Metabolism and Molecular Medicine, The Ministry of Education, Department of Biochemistry and Molecular Biology, Fudan University Shanghai Medical College, Shanghai 200032, PR China.
authors: Jue
authors: J
authors: Wang
authors: Shanghai Key Laboratory of Female Reproductive Endocrine Related Disease, Obstetrics and Gynecology Hospital of Fudan University, Shanghai 200090, PR China.
authors: Ji-Chan
authors: JC
authors: Nie
authors: Key Laboratory of Metabolism and Molecular Medicine, The Ministry of Education, Department of Biochemistry and Molecular Biology, Fudan University Shanghai Medical College, Shanghai 200032, PR China.
authors: Meng-Yuan
authors: MY
authors: Wu
authors: Key Laboratory of Metabolism and Molecular Medicine, The Ministry of Education, Department of Biochemistry and Molecular Biology, Fudan University Shanghai Medical College, Shanghai 200032, PR China.
authors: Yan
authors: Y
authors: Tang
authors: Key Laboratory of Metabolism and Molecular Medicine, The Ministry of Education, Department of Biochemistry and Molecular Biology, Fudan University Shanghai Medical College, Shanghai 200032, PR China.
authors: Ya-Xin
authors: YX
authors: Zhao
authors: Key Laboratory of Metabolism and Molecular Medicine, The Ministry of Education, Department of Biochemistry and Molecular Biology, Fudan University Shanghai Medical College, Shanghai 200032, PR China.
authors: Xi
authors: X
authors: Li
authors: Key Laboratory of Metabolism and Molecular Medicine, The Ministry of Education, Department of Biochemistry and Molecular Biology, Fudan University Shanghai Medical College, Shanghai 200032, PR China.
authors: Hai-Yan
authors: HY
authors: Huang
authors: Key Laboratory of Metabolism and Molecular Medicine, The Ministry of Education, Department of Biochemistry and Molecular Biology, Fudan University Shanghai Medical College, Shanghai 200032, PR China.
authors: Liang
authors: L
authors: Guo
authors: Shanghai Key Laboratory of Female Reproductive Endocrine Related Disease, Obstetrics and Gynecology Hospital of Fudan University, Shanghai 200090, PR China.
authors: Xi-Shi
authors: XS
authors: Liu
authors: Shanghai Key Laboratory of Female Reproductive Endocrine Related Disease, Obstetrics and Gynecology Hospital of Fudan University, Shanghai 200090, PR China.
authors: Cong-Jian
authors: CJ
authors: Xu
authors: Key Laboratory of Metabolism and Molecular Medicine, The Ministry of Education, Department of Biochemistry and Molecular Biology, Fudan University Shanghai Medical College, Shanghai 200032, PR China. Electronic address: qqtang@shmu.edu.cn.
authors: Qi-Qun
authors: QQ
authors: Tang
mesh_terms: D017667:Adipocytes / Q000378:metabolism; D000273:Adipose Tissue / Q000378:metabolism; D050154:Adiposity / Q000235:genetics; D000367:Age Factors; D000818:Animals; D015992:Body Mass Index; D055415:Bone Morphogenetic Protein 4 / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D059305:Diet, High-Fat; D047628:Estrogen Receptor alpha / Q000378:metabolism*; D004967:Estrogens / Q000378:metabolism* / Q000494:pharmacology; D005260:Female; D005786:Gene Expression Regulation; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D007333:Insulin Resistance; D008659:Metabolic Diseases / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D023421:Models, Animal; D009765:Obesity / Q000378:metabolism; D011485:Protein Binding; D055550:Protein Stability; D015398:Signal Transduction
chemical_list: D055415:Bone Morphogenetic Protein 4; D047628:Estrogen Receptor alpha; D004967:Estrogens; D005947:Glucose
keywords: BMP4; ERα; Estrogen; Glucose metabolism; White adipose tissue