| Literature DB >> 24906147 |
Rajesh R Rao1, Jonathan Z Long1, James P White1, Katrin J Svensson1, Jesse Lou1, Isha Lokurkar1, Mark P Jedrychowski2, Jorge L Ruas3, Christiane D Wrann1, James C Lo1, Donny M Camera4, Jenn Lachey5, Steven Gygi2, Jasbir Seehra5, John A Hawley6, Bruce M Spiegelman7.
Abstract
Exercise training benefits many organ systems and offers protection against metabolic disorders such as obesity and diabetes. Using the recently identified isoform of PGC1-α (PGC1-α4) as a discovery tool, we report the identification of meteorin-like (Metrnl), a circulating factor that is induced in muscle after exercise and in adipose tissue upon cold exposure. Increasing circulating levels of Metrnl stimulates energy expenditure and improves glucose tolerance and the expression of genes associated with beige fat thermogenesis and anti-inflammatory cytokines. Metrnl stimulates an eosinophil-dependent increase in IL-4 expression and promotes alternative activation of adipose tissue macrophages, which are required for the increased expression of the thermogenic and anti-inflammatory gene programs in fat. Importantly, blocking Metrnl actions in vivo significantly attenuates chronic cold-exposure-induced alternative macrophage activation and thermogenic gene responses. Thus, Metrnl links host-adaptive responses to the regulation of energy homeostasis and tissue inflammation and has therapeutic potential for metabolic and inflammatory diseases.Entities:
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Year: 2014 PMID： 24906147 PMCID： PMC4131287 DOI： 10.1016/j.cell.2014.03.065
Source DB: PubMed Journal: Cell ISSN： 0092-8674 Impact factor: 41.582