Authors: Tim J Schulz Antonia Graja Tian Lian Huang Ruidan Xue Ding An Sophie PoehleKronawitter Matthew D Lynes Alexander Tolkachov Lindsay E O’Sullivan Michael F Hirshman Michael Schupp Laurie J Goodyear Yuji Mishina YuHua Tseng
Publish Date: 2016/05/21
Volume: 59, Issue: 8, Pages: 1769-1777
Abstract
Adipose tissue dysfunction is a prime risk factor for the development of metabolic disease Bone morphogenetic proteins BMPs have previously been implicated in adipocyte formation Here we investigate the role of BMP signalling in adipose tissue health and systemic glucose homeostasisWe employed the Cre/loxP system to generate mouse models with conditional ablation of BMP receptor 1A in differentiating and mature adipocytes as well as tissueresident myeloid cells Metabolic variables were assessed by glucose and insulin tolerance testing insulinstimulated glucose uptake and gene expression analysisConditional deletion of Bmpr1a using the aP2 also known as Fabp4Cre strain resulted in a complex phenotype Knockout mice were clearly resistant to agerelated impairment of insulin sensitivity during normal and highfatdiet feeding and showed significantly improved insulinstimulated glucose uptake in brown adipose tissue and skeletal muscle Moreover knockouts displayed significant reduction of variables of adipose tissue inflammation Deletion of Bmpr1a in myeloid cells had no impact on insulin sensitivity while ablation of Bmpr1a in mature adipocytes partially recapitulated the initial phenotype from aP2Cre driven deletion Cocultivation of macrophages with preadipocytes lacking Bmpr1a markedly reduced expression of proinflammatory genesOur findings show that altered BMP signalling in adipose tissue affects the tissue’s metabolic properties and systemic insulin resistance by altering the pattern of immune cell infiltration The phenotype is due to ablation of Bmpr1a specifically in preadipocytes and maturing adipocytes rather than an immune cellautonomous effect Mechanistically we provide evidence for a BMPmediated direct crosstalk between preadipocytes and macrophages
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