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Mfge8 promotes obesity by mediating the uptake of dietary fats and serum fatty acids
- Source :
- Nature Medicine. 20:175-183
- Publication Year :
- 2014
- Publisher :
- Springer Science and Business Media LLC, 2014.
-
Abstract
- Fatty acids are integral mediators of energy storage, membrane formation and cell signaling. The pathways that orchestrate uptake of fatty acids remain incompletely understood. Expression of the integrin ligand Mfge8 is increased in human obesity and in mice on a high-fat diet, but its role in obesity is unknown. We show here that Mfge8 promotes the absorption of dietary triglycerides and the cellular uptake of fatty acid and that Mfge8-deficient (Mfge8(-/-)) mice are protected from diet-induced obesity, steatohepatitis and insulin resistance. Mechanistically, we found that Mfge8 coordinates fatty acid uptake through αvβ3 integrin- and αvβ5 integrin-dependent phosphorylation of Akt by phosphatidylinositide-3 kinase and mTOR complex 2, leading to translocation of Cd36 and Fatp1 from cytoplasmic vesicles to the cell surface. Collectively, our results imply a role for Mfge8 in regulating the absorption and storage of dietary fats, as well as in the development of obesity and its complications.
- Subjects :
- Blood Glucose
Blotting, Western
Adipose tissue
Mechanistic Target of Rapamycin Complex 2
Biology
Cell Fractionation
Real-Time Polymerase Chain Reaction
Article
General Biochemistry, Genetics and Molecular Biology
Mice
chemistry.chemical_compound
Insulin resistance
3T3-L1 Cells
In Situ Nick-End Labeling
medicine
Animals
Carbon Radioisotopes
Obesity
Phosphorylation
adipocyte protein 2
Triglycerides
DNA Primers
Mice, Knockout
chemistry.chemical_classification
Analysis of Variance
Microscopy, Confocal
TOR Serine-Threonine Kinases
Fatty Acids
Fatty acid
General Medicine
Flow Cytometry
Microarray Analysis
Milk Proteins
medicine.disease
Dietary Fats
Immunohistochemistry
Oncogene Protein v-akt
Oleic acid
chemistry
Biochemistry
Multiprotein Complexes
Antigens, Surface
Body Composition
biology.protein
Phosphatidylinositol 3-Kinase
MFGE8
Oleic Acid
Subjects
Details
- ISSN :
- 1546170X and 10788956
- Volume :
- 20
- Database :
- OpenAIRE
- Journal :
- Nature Medicine
- Accession number :
- edsair.doi.dedup.....bda51e2f1d099af218f4ae564264d831