title: Identification of BMP and activin membrane-bound inhibitor (BAMBI) as a potent negative regulator of adipogenesis and modulator of autocrine/paracrine adipogenic factors.
abstract: Adipose tissue dysfunction underpins the association of obesity with type 2 diabetes. Adipogenesis is required for the maintenance of adipose tissue function. It involves the commitment and subsequent differentiation of preadipocytes and is coordinated by autocrine, paracrine, and endocrine factors. We previously reported that fibroblast growth factor-1 (FGF-1) primes primary human preadipocytes and Simpson Golabi Behmel syndrome (SGBS) preadipocytes and increases adipogenesis through a cascade involving extracellular signal-related kinase 1/2 (ERK1/2). Here, we aimed to use the FGF-1 system to identify novel adipogenic regulators. Expression profiling revealed bone morphogenetic protein (BMP) and activin membrane-bound inhibitor (BAMBI) as a putative FGF-1 effector. BAMBI is a transmembrane protein and modulator of paracrine factors that regulate adipogenesis, including transforming growth factor (TGF) superfamily members (TGF-β and BMP) and Wnt. Functional investigations established BAMBI as a negative regulator of adipogenesis and modulator of the anti- and proadipogenic effects of Wnt3a, TGF-β1, and BMP-4. Further studies showed that BAMBI expression levels are decreased in a mouse model of diet-induced obesity. Collectively, these findings establish BAMBI as a novel, negative regulator of adipogenesis that can act as a nexus to integrate multiple paracrine signals to coordinate adipogenesis. Alterations in BAMBI may play a role in the (patho)physiology of obesity, and manipulation of BAMBI may present a novel therapeutic approach to improve adipose tissue function.
authors.affiliation: Laboratory of Animal Fat Deposition and Muscle Development, College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, People's Republic of China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Luo
authors.forename: Louise J
authors.initials: LJ
authors.lastname: Hutley
authors.forename: Julie A
authors.initials: JA
authors.lastname: Webster
authors.forename: Yu-Hee
authors.initials: YH
authors.lastname: Kim
authors.forename: Dong-Fang
authors.initials: DF
authors.lastname: Liu
authors.forename: Felicity S
authors.initials: FS
authors.lastname: Newell
authors.forename: Charlotte H
authors.initials: CH
authors.lastname: Widberg
authors.forename: Anthony
authors.initials: A
authors.lastname: Bachmann
authors.forename: Nigel
authors.initials: N
authors.lastname: Turner
authors.forename: Carsten
authors.initials: C
authors.lastname: Schmitz-Peiffer
authors.forename: Johannes B
authors.initials: JB
authors.lastname: Prins
authors.forename: Gong-She
authors.initials: GS
authors.lastname: Yang
authors.forename: Jonathan P
authors.initials: JP
authors.lastname: Whitehead
mesh_terms: D050156:Adipogenesis / Q000187:drug effects / Q000235:genetics*; D054392:Adipokines / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D019898:Autocrine Communication / Q000187:drug effects / Q000235:genetics*; D002478:Cells, Cultured; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics; D055785:Gene Knockdown Techniques; D006801:Humans; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000302:isolation & purification / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D009765:Obesity / Q000235:genetics / Q000378:metabolism; D019899:Paracrine Communication / Q000187:drug effects / Q000235:genetics*; D034741:RNA, Small Interfering / Q000494:pharmacology
chemical_list: D054392:Adipokines; C485671:BAMBI protein, human; D008565:Membrane Proteins; D034741:RNA, Small Interfering