Adipocyte-secreted BMP8b mediates adrenergic-induced remodeling of the neuro-vascular network in adipose tissue.
Vanessa PellegrinelliVivian J PeirceLaura HowardSamuel VirtueDénes TüreiMartina SenzacquaAndrea FrontiniJeffrey W DalleyAntony R HortonGuillaume BidaultIlenia SeveriAndrew WhittleKamal RahmouniJulio Saez-RodriguezSaverio CintiAlun M DaviesAntonio Vidal-PuigPublished in: Nature communications (2018)
Activation of brown adipose tissue-mediated thermogenesis is a strategy for tackling obesity and promoting metabolic health. BMP8b is secreted by brown/beige adipocytes and enhances energy dissipation. Here we show that adipocyte-secreted BMP8b contributes to adrenergic-induced remodeling of the neuro-vascular network in adipose tissue (AT). Overexpression of bmp8b in AT enhances browning of the subcutaneous depot and maximal thermogenic capacity. Moreover, BMP8b-induced browning, increased sympathetic innervation and vascularization of AT were maintained at 28 °C, a condition of low adrenergic output. This reinforces the local trophic effect of BMP8b. Innervation and vascular remodeling effects required BMP8b signaling through the adipocytes to 1) secrete neuregulin-4 (NRG4), which promotes sympathetic axon growth and branching in vitro, and 2) induce a pro-angiogenic transcriptional and secretory profile that promotes vascular sprouting. Thus, BMP8b and NRG4 can be considered as interconnected regulators of neuro-vascular remodeling in AT and are potential therapeutic targets in obesity.
Keyphrases
- adipose tissue
- insulin resistance
- mesenchymal stem cells
- bone regeneration
- high fat diet induced
- high fat diet
- high glucose
- diabetic rats
- type diabetes
- public health
- healthcare
- metabolic syndrome
- drug induced
- gene expression
- transcription factor
- skeletal muscle
- risk assessment
- fatty acid
- bone marrow
- blood pressure
- endothelial cells
- human health
- body composition
- climate change
- social media
- health promotion