| First Author | Chen Y | Year | 2019 |
| Journal | FASEB J | Volume | 33 |
| Issue | 12 | Pages | 13722-13733 |
| PubMed ID | 31585505 | Mgi Jnum | J:298723 |
| Mgi Id | MGI:6472487 | Doi | 10.1096/fj.201901474RR |
| Citation | Chen Y, et al. (2019) Deficiency in the short-chain acyl-CoA dehydrogenase protects mice against diet-induced obesity and insulin resistance. FASEB J 33(12):13722-13733 |
| abstractText | Acyl-CoA dehydrogenases (CADs) participate in mitochondrial fatty acid oxidation; abnormal fatty acid oxidation is associated with obesity and related metabolic disorders. We decipher the impact of short-chain CAD (SCAD) on adiposity and insulin resistance. BALB/cBy strain mice derived from BALB/c strain are deficient in SCAD activity because of a spontaneous deletion in the acyl-CoA dehydrogenases (Acads) gene. Adiposity, lipogenesis, and insulin sensitivity were compared in BALB/c and BALB/cBy mice subjected to high-fat diets (HFDs). A whole hepatic transcriptome profiling experiment with microarrays was performed to evaluate the mechanisms by which SCAD deficiency protects against insulin resistance. Acads-deficient mice were significantly resistant to HFD-induced obesity and insulin resistance as compared with control mice. Reduced obesity results from decreased triglyceride content due to activation of AMPK in liver that would reduce hepatic content of malonyl-CoA, resulting in decreased hepatic de novo lipogenesis. Improved insulin sensitivity was associated with reduced diacylglycerol content commensurate with reduced PKC-epsilon activity and increased protein kinase B (AKT) activation in liver and skeletal muscle. Additionally, Acads-deficient mice displayed significantly higher expression of the endoplasmic chaperone 78-kDa glucose-regulated protein, which was further associated with the AKT activation in the primary hepatocytes. Modulation of SCAD expression may therefore be a novel therapeutic approach to manage and prevent obesity and related metabolic diseases, such as diabetes.-Chen, Y., Chen, J., Zhang, C., Yang, S., Zhang, X., Liu, Y., Su, Z. Deficiency in the short-chain acyl-CoA dehydrogenase protects mice against diet-induced obesity and insulin resistance. |
