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Irisin Stimulates Browning of White Adipocytes Through Mitogen-Activated Protein Kinase p38 MAP Kinase and ERK MAP Kinase Signaling
- Source :
- Diabetes
- Publication Year :
- 2014
- Publisher :
- American Diabetes Association, 2014.
-
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.
- Subjects :
- Male
MAPK/ERK pathway
medicine.medical_specialty
MAP Kinase Signaling System
Pyridines
Betatrophin
Adipose Tissue, White
Endocrinology, Diabetes and Metabolism
Adipose tissue
White adipose tissue
Biology
p38 Mitogen-Activated Protein Kinases
Pichia
Rats, Sprague-Dawley
Mice
Adipose Tissue, Brown
3T3-L1 Cells
Commentaries
Internal medicine
Nitriles
Adipocytes
Butadienes
Internal Medicine
medicine
Animals
Glucose homeostasis
Caenorhabditis elegans Proteins
Extracellular Signal-Regulated MAP Kinases
Protein kinase A
Kinase
Imidazoles
Membrane Transport Proteins
Dietary Fats
FNDC5
Recombinant Proteins
Fibronectins
Rats
Mice, Inbred C57BL
Endocrinology
Mutation
Mitochondrial Uncoupling Proteins
Protein Binding
Subjects
Details
- ISSN :
- 1939327X and 00121797
- Volume :
- 63
- Database :
- OpenAIRE
- Journal :
- Diabetes
- Accession number :
- edsair.doi.dedup.....2bc8cc474869726dce6d6eead421644a
- Full Text :
- https://doi.org/10.2337/db13-1106