| First Author | Drosatos K | Year | 2011 |
| Journal | Am J Physiol Endocrinol Metab | Volume | 300 |
| Issue | 3 | Pages | E489-99 |
| PubMed ID | 21139071 | Mgi Jnum | J:172319 |
| Mgi Id | MGI:5006911 | Doi | 10.1152/ajpendo.00569.2010 |
| Citation | Drosatos K, et al. (2011) Cardiomyocyte lipids impair beta-adrenergic receptor function via PKC activation. Am J Physiol Endocrinol Metab 300(3):E489-99 |
| abstractText | Normal hearts have increased contractility in response to catecholamines. Because several lipids activate PKCs, we hypothesized that excess cellular lipids would inhibit cardiomyocyte responsiveness to adrenergic stimuli. Cardiomyocytes treated with saturated free fatty acids, ceramide, and diacylglycerol had reduced cellular cAMP response to isoproterenol. This was associated with increased PKC activation and reduction of beta-adrenergic receptor (beta-AR) density. Pharmacological and genetic PKC inhibition prevented both palmitate-induced beta-AR insensitivity and the accompanying reduction in cell surface beta-ARs. Mice with excess lipid uptake due to either cardiac-specific overexpression of anchored lipoprotein lipase, PPARgamma, or acyl-CoA synthetase-1 or high-fat diet showed reduced inotropic responsiveness to dobutamine. This was associated with activation of protein kinase C (PKC)alpha or PKCdelta. Thus, several lipids that are increased in the setting of lipotoxicity can produce abnormalities in beta-AR responsiveness. This can be attributed to PKC activation and reduced beta-AR levels. |
