| First Author | Jiang LQ | Year | 2016 |
| Journal | Am J Physiol Endocrinol Metab | Volume | 310 |
| Issue | 1 | Pages | E51-60 |
| PubMed ID | 26530149 | Mgi Jnum | J:235824 |
| Mgi Id | MGI:5803760 | Doi | 10.1152/ajpendo.00209.2015 |
| Citation | Jiang LQ, et al. (2016) Diacylglycerol kinase-delta regulates AMPK signaling, lipid metabolism, and skeletal muscle energetics. Am J Physiol Endocrinol Metab 310(1):E51-60 |
| abstractText | Decrease of AMPK-related signal transduction and insufficient lipid oxidation contributes to the pathogenesis of obesity and type 2 diabetes. Previously, we identified that diacylglycerol kinase-delta (DGKdelta), an enzyme involved in triglyceride biosynthesis, is reduced in skeletal muscle from type 2 diabetic patients. Here, we tested the hypothesis that DGKdelta plays a role in maintaining appropriate AMPK action in skeletal muscle and energetic aspects of contraction. Voluntary running activity was reduced in DGKdelta(+/-) mice, but glycogen content and mitochondrial markers were unaltered, suggesting that DGKdelta deficiency affects skeletal muscle energetics but not mitochondrial protein abundance. We next determined the role of DGKdelta in AMPK-related signal transduction and lipid metabolism in isolated skeletal muscle. AMPK activation and signaling were reduced in DGKdelta(+/-) mice, concomitant with impaired lipid oxidation and elevated incorporation of free fatty acids into triglycerides. Strikingly, DGKdelta deficiency impaired work performance, as evident by altered force production and relaxation dynamics in response to repeated contractions. In conclusion, DGKdelta deficiency impairs AMPK signaling and lipid metabolism, thereby highlighting the deleterious role of excessive lipid metabolites in the development of peripheral insulin resistance and type 2 diabetes pathogenesis. DGKdelta deficiency also influences skeletal muscle energetics, which may lead to low physical activity levels in type 2 diabetes. |
