beta-Agonist stimulation produces changes in cardiac AMPK and coronary lumen LPL only during increased workload

• Published in: American journal of physiology: endocrinology and metabolism 2005-06, Vol.288 (6), p.E1120-E1127
• Main Authors: An, Ding, Kewalramani, Girsh, Qi, Dake, Pulinilkunnil, Thomas, Ghosh, Sanjoy, Abrahani, Ashraf, Wambolt, Rich, Allard, Michael, Innis, Sheila M, Rodrigues, Brian
• Format: Article
• Language: English
• Subjects: Acetyl-CoA Carboxylase - metabolism; Adrenergic beta-Agonists - pharmacology; AMP-Activated Protein Kinases; Animals; Blotting, Western; Endothelium, Vascular - metabolism; Heart - drug effects; Heart - physiology; In Vitro Techniques; Isoproterenol - pharmacology; Lipoprotein Lipase - genetics; Lipoprotein Lipase - metabolism; Male; Multienzyme Complexes - metabolism; Myocardial Contraction - drug effects; Myocardial Contraction - physiology; Myocardium - enzymology; Myocytes, Cardiac - enzymology; Phosphorylation; Physical Conditioning, Animal - physiology; Protein-Serine-Threonine Kinases - metabolism; Rats; Rats, Wistar; Reverse Transcriptase Polymerase Chain Reaction; RNA - chemistry; RNA - genetics; Stimulation, Chemical
• ISSN: 0193-1849; 1522-1555
• DOI: 10.1152/ajpendo.00588.2004

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.