| First Author | Bednarski T | Year | 2016 |
| Journal | Biochim Biophys Acta | Volume | 1861 |
| Issue | 12 Pt A | Pages | 2029-2037 |
| PubMed ID | 27751891 | Mgi Jnum | J:250692 |
| Mgi Id | MGI:6105699 | Doi | 10.1016/j.bbalip.2016.10.005 |
| Citation | Bednarski T, et al. (2016) Stearoyl-CoA desaturase 1 deficiency reduces lipid accumulation in the heart by activating lipolysis independently of peroxisome proliferator-activated receptor alpha. Biochim Biophys Acta 1861(12 Pt A):2029-2037 |
| abstractText | Stearoyl-CoA desaturase 1 (SCD1) has recently been shown to be a critical control point in the regulation of cardiac metabolism and function. Peroxisome proliferator-activated receptor alpha (PPARalpha) is an important regulator of myocardial fatty acid uptake and utilization. The present study used SCD1 and PPARalpha double knockout (SCD1(-/-)/PPARalpha(-/-)) mice to test the hypothesis that PPARalpha is involved in metabolic changes in the heart that are caused by SCD1 downregulation/inhibition. SCD1 deficiency decreased the intracellular content of free fatty acids, triglycerides, and ceramide in the heart of SCD1(-/-) and SCD1(-/-)/PPARalpha(-/-) mice. SCD1 ablation in PPARalpha(-/-) mice decreased diacylglycerol content in cardiomyocytes. These results indicate that the reduction of fat accumulation in the heart associated with SCD1 deficiency occurs independently of the PPARalpha pathway. To elucidate the mechanism of the observed changes, we treated HL-1 cardiomyocytes with the SCD1 inhibitor A939572 and/or PPARalpha inhibitor GW6471. SCD1 inhibition decreased the level of lipogenic proteins and increased lipolysis, reflected by a decrease in the content of adipose triglyceride lipase inhibitor G0S2 and a decrease in the ratio of phosphorylated hormone-sensitive lipase (HSL) at Ser565 to HSL (pHSL[Ser565]/HSL). PPARalpha inhibition alone did not affect the aforementioned protein levels. Finally, PPARalpha inhibition decreased the phosphorylation level of 5''-adenosine monophosphate-activated protein kinase, indicating lower mitochondrial fatty acid oxidation. In summary, SCD1 ablation/inhibition decreased cardiac lipid content independently of the action of PPARalpha by reducing lipogenesis and activating lipolysis. The present data suggest that SCD1 is an important component in maintaining proper cardiac lipid metabolism. |
