title: Meteorin-like is a hormone that regulates immune-adipose interactions to increase beige fat thermogenesis.
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.
authors.affiliation: Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02115, USA; Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Rajesh R
authors.initials: RR
authors.lastname: Rao
authors.affiliation: Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02115, USA; Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Jonathan Z
authors.initials: JZ
authors.lastname: Long
authors.affiliation: Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02115, USA; Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: James P
authors.initials: JP
authors.lastname: White
authors.affiliation: Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02115, USA; Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Katrin J
authors.initials: KJ
authors.lastname: Svensson
authors.affiliation: Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02115, USA; Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Jesse
authors.initials: J
authors.lastname: Lou
authors.affiliation: Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02115, USA; Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Isha
authors.initials: I
authors.lastname: Lokurkar
authors.affiliation: Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Mark P
authors.initials: MP
authors.lastname: Jedrychowski
authors.affiliation: Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm 171-77, Sweden.
authors.forename: Jorge L
authors.initials: JL
authors.lastname: Ruas
authors.affiliation: Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02115, USA; Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Christiane D
authors.initials: CD
authors.lastname: Wrann
authors.affiliation: Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02115, USA; Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: James C
authors.initials: JC
authors.lastname: Lo
authors.affiliation: Exercise and Nutrition Research Group, Department of Exercise Sciences, Australian Catholic University, Fitzroy, Victoria 3065, Australia.
authors.forename: Donny M
authors.initials: DM
authors.lastname: Camera
authors.affiliation: Ember Therapeutics, Inc., 480 Arsenal Street, Building 1, Suite 101, Watertown, MA 02472, USA.
authors.forename: Jenn
authors.initials: J
authors.lastname: Lachey
authors.affiliation: Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Steven
authors.initials: S
authors.lastname: Gygi
authors.affiliation: Ember Therapeutics, Inc., 480 Arsenal Street, Building 1, Suite 101, Watertown, MA 02472, USA.
authors.forename: Jasbir
authors.initials: J
authors.lastname: Seehra
authors.affiliation: Exercise and Nutrition Research Group, Department of Exercise Sciences, Australian Catholic University, Fitzroy, Victoria 3065, Australia; Research Institute for Sport and Exercise Sciences, Liverpool John Moores University, Liverpool L3 2AJ, UK.
authors.forename: John A
authors.initials: JA
authors.lastname: Hawley
authors.affiliation: Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02115, USA; Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA. Electronic address: bruce_spiegelman@dfci.harvard.edu.
authors.forename: Bruce M
authors.initials: BM
authors.lastname: Spiegelman
mesh_terms: D002001:Adipose Tissue, Brown / Q000378:metabolism*; D000818:Animals; D005947:Glucose / Q000378:metabolism; D018793:Interleukin-13 / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D018482:Muscle, Skeletal / Q000378:metabolism; D009414:Nerve Growth Factors / Q000235:genetics / Q000378:metabolism*; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D022722:Thermogenesis; D014157:Transcription Factors / Q000235:genetics
chemical_list: D018793:Interleukin-13; D009414:Nerve Growth Factors; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C485290:Ppargc1a protein, mouse; D014157:Transcription Factors; C570859:cometin protein, mouse; D015847:Interleukin-4; D005947:Glucose