title: Irisin stimulates browning of white adipocytes through mitogen-activated protein kinase p38 MAP kinase and ERK MAP kinase signaling.
abstract: The number and activity of brown adipocytes are linked to the ability of mammals to resist body fat accumulation. In some conditions, certain white adipose tissue (WAT) depots are readily convertible to a ''brown-like'' state, which is associated with weight loss. Irisin, a newly identified hormone, is secreted by skeletal muscles into circulation and promotes WAT "browning" with unknown mechanisms. In the current study, we demonstrated in mice that recombinant irisin decreased the body weight and improved glucose homeostasis. We further showed that irisin upregulated uncoupling protein-1 (UCP-1; a regulator of thermogenic capability of brown fat) expression. This effect was possibly mediated by irisin-induced phosphorylation of the p38 mitogen-activated protein kinase (p38 MAPK) and extracellular signal-related kinase (ERK) signaling pathways. Inhibition of the p38 MAPK by SB203580 and ERK by U0126 abolished the upregulatory effect of irisin on UCP-1. In addition, irisin also promoted the expression of betatrophin, another newly identified hormone that promotes pancreatic β-cell proliferation and improves glucose tolerance. In summary, our data suggest that irisin can potentially prevent obesity and associated type 2 diabetes by stimulating expression of WAT browning-specific genes via the p38 MAPK and ERK pathways.
authors.affiliation: Center for Stem Cell and Regenerative Medicine, The Second Hospital of Shandong University, Jinan, People's Republic of China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Rui
authors.initials: R
authors.lastname: Li
authors.forename: Yan
authors.initials: Y
authors.lastname: Meng
authors.forename: Shiwu
authors.initials: S
authors.lastname: Li
authors.forename: William
authors.initials: W
authors.lastname: Donelan
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhao
authors.forename: Lei
authors.initials: L
authors.lastname: Qi
authors.forename: Mingxiang
authors.initials: M
authors.lastname: Zhang
authors.forename: Xingli
authors.initials: X
authors.lastname: Wang
authors.forename: Taixing
authors.initials: T
authors.lastname: Cui
authors.forename: Li-Jun
authors.initials: LJ
authors.lastname: Yang
authors.forename: Dongqi
authors.initials: D
authors.lastname: Tang
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D002001:Adipose Tissue, Brown / Q000187:drug effects / Q000378:metabolism; D052436:Adipose Tissue, White / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D002070:Butadienes / Q000494:pharmacology; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism; D004041:Dietary Fats; D048049:Extracellular Signal-Regulated MAP Kinases / Q000235:genetics / Q000378:metabolism*; D005353:Fibronectins / Q000008:administration & dosage / Q000235:genetics / Q000494:pharmacology*; D007093:Imidazoles / Q000494:pharmacology; D020935:MAP Kinase Signaling System / Q000502:physiology*; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D000071245:Mitochondrial Uncoupling Proteins; D009154:Mutation; D009570:Nitriles / Q000494:pharmacology; D010843:Pichia / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*
chemical_list: D002070:Butadienes; D029742:Caenorhabditis elegans Proteins; D004041:Dietary Fats; C577593:FNDC5 protein, human; D005353:Fibronectins; D007093:Imidazoles; D026901:Membrane Transport Proteins; D000071245:Mitochondrial Uncoupling Proteins; D009570:Nitriles; D011725:Pyridines; D011994:Recombinant Proteins; C113580:U 0126; C507109:UCP-4 protein, C elegans; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580