Mfge8 promotes obesity by mediating the uptake of dietary fats and serum fatty acids
| العنوان: | Mfge8 promotes obesity by mediating the uptake of dietary fats and serum fatty acids |
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| المؤلفون: | Kevin M. Tharp, Andreas Stahl, Kamran Atabai, Stephen Sakuma, Scott M. Turner, Yuk Yin Cheung, Ajay Chawla, Amin Khalifeh-Soltani, Yifu Qiu, William McKleroy |
| المصدر: | Nature Medicine. 20:175-183 |
| بيانات النشر: | Springer Science and Business Media LLC, 2014. |
| سنة النشر: | 2014 |
| مصطلحات موضوعية: | 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 |
| الوصف: | 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. |
| تدمد: | 1546-170X 1078-8956 |
| DOI: | 10.1038/nm.3450 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::bda51e2f1d099af218f4ae564264d831 https://doi.org/10.1038/nm.3450 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....bda51e2f1d099af218f4ae564264d831 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 1546170X 10788956 |
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| DOI: | 10.1038/nm.3450 |