Adipocyte-secreted BMP8b mediates adrenergic-induced remodeling of the neuro-vascular network in adipose tissue.

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.

An analysis of global research funding for the frontotemporal dementias: 1998-2008.

BACKGROUND: To better understand the status of frontotemporal dementia (FTD) research, and identify opportunities to accelerate translational research, we analyzed international funding for FTD and related dementias between 1998 and 2008. METHODS: Search terms were compiled to define the clinical spectrum of FTD and all known mechanisms. Funders were asked to return grants that contained these search terms in the title or abstract. Grants were classified according to the most reasonably achieved stated aim using a classification scheme of research activities that was developed to map grants along the continuum from basic research to clinical trials of treatments. RESULTS: This analysis captured 613 grants ($432,167,275), from 19 private and public funders from 7 countries and the European Union. National Institutes of Health contributed $360 million (MM), 53% of grants and 83% of total funding. Foundations contributed $43 MM, 35% of grants and 10% of total funding, an increase in recent years. A total of $319 MM (74%, funding) went toward basic research, of which 10% was dedicated to preclinical treatment development, clinical treatment evaluation, and developing detection, diagnostic, and imaging technologies and reagents. CONCLUSIONS: FTD received moderate funding over the past decade, which has decreased almost five-fold during this period. A sizable proportion of FTD funding supported mechanisms shared with Alzheimer's disease. Few programs advanced past validating target models and into drug discovery and preclinical development, indicating that the knowledge gained from recent research has still not advanced into treatment development. Quantitative analysis of funding highlighted under-resourced areas as well as redundant efforts, enabling a more strategic approach toward advancing FTD drug discovery and development.