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| Status |
Public on Feb 09, 2017 |
| Title |
Effect of Mut heterozygosity in skeletal muscle gene expression |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
Branched-chain amino acids (BCAA) have emerged as predictors of type 2 diabetes (T2D). However, their potential role in the pathogenesis of insulin resistance and T2D remains unclear. By integrating data from skeletal muscle gene expression and metabolomic analyses, we demonstrate evidence for perturbation in BCAA metabolism and fatty acid oxidation in skeletal muscle from insulin-resistant humans. Experimental modulation of BCAA flux in cultured cells alters fatty acid oxidation in parallel. Furthermore, heterozygosity for the BCAA metabolic enzyme methylmalonyl-CoA mutase (MUT) alters muscle lipid metabolism in vivo, resulting in increased muscle triacylglycerol (TAG) accumulation and increased body weight after high-fat feeding. Together, our results demonstrate that impaired muscle BCAA catabolism may contribute to the development of insulin resistance by reducing fatty acid oxidation and increasing TAG accumulation.
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| Overall design |
5-week-old Mut+/+ and Mut+/- male mice were fed a high-fat diet with 45% kcal from fat for 4 months. Mice were fasted overnight prior to sacrifice and quadriceps muscle was flash frozen in liquid nitrogen.
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| Contributor(s) |
Lerin C, Venditti CP, Patti ME |
| Citation(s) |
27689005 |
| |
| Submission date |
Mar 10, 2015 |
| Last update date |
Feb 11, 2019 |
| Contact name |
Grace Daher |
| Organization name |
Joslin Diabetes Center
|
| Street address |
1 Joslin Place
|
| City |
Boston |
| ZIP/Postal code |
02215 |
| Country |
USA |
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| Platforms (1) |
| GPL1261 |
[Mouse430_2] Affymetrix Mouse Genome 430 2.0 Array |
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| Samples (10)
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| Relations |
| BioProject |
PRJNA277882 |
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