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  • Title: beta-Agonist stimulation produces changes in cardiac AMPK and coronary lumen LPL only during increased workload.
    Author: An D, Kewalramani G, Qi D, Pulinilkunnil T, Ghosh S, Abrahani A, Wambolt R, Allard M, Innis SM, Rodrigues B.
    Journal: Am J Physiol Endocrinol Metab; 2005 Jun; 288(6):E1120-7. PubMed ID: 15687106.
    Abstract:
    Given the importance of lipoprotein lipase (LPL) in cardiac and vascular pathology, the objective of the present study was to investigate whether the beta-agonist isoproterenol (Iso) influences cardiac LPL. Incubation of quiescent cardiomyocytes with Iso for 60 min had no effect on basal, intracellular, or heparin-releasable (HR)-LPL activity. Similarly, Iso did not change HR-LPL in Langendorff isolated hearts that do not beat against an afterload. In the intact animal, LPL activity at the vascular lumen increased significantly in the Iso-treated group, together with a substantial increase in rate-pressure product. This LPL increase was likely via mechanisms regulated by activation of AMP-activated protein kinase (AMPK) and inactivation of acetyl-CoA carboxylase (ACC280). In glucose-perfused hearts, simply switching from Langendorff to the isolated working heart (that beats against an afterload) induced increases in AMPK and ACC280 phosphorylation and enhanced HR-LPL activity. Provision of insulin and albumin-bound palmitic acid to the working heart was able to reverse these effects. In these hearts, introduction of Iso to the buffer perfusate duplicated the effects seen when this beta-agonist was given in vivo. Our data suggest that Iso can influence HR-LPL only during conditions of increased workload, mechanical performance and excessive energy expenditure, and likely in an AMPK-dependent manner.
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