The metabolic "switch" AMPK regulates cardiac heparin-releasable lipoprotein lipase.
The "fuel gauge" AMP-activated protein kinase (AMPK) facilitates ATP production to meet energy demands during metabolic stress. Given the importance of lipoprotein lipase (LPL) in providing hearts with fatty acids (FA), the preferred substrate consumed by the heart, the objective of the present study was to investigate whether activation of AMPK influences LPL at its functionally relevant location, the coronary lumen. Hearts from overnight-fasted rats were first perfused with heparin to release LPL, and homogenates from these hearts were then used to measure total and phospho-AMPK-alpha by Western blotting. Manipulation of AMPK activity [with drugs like adenine 9-beta-D-arabinofuranoside (Ara-A) and insulin (that inhibit) or perhexiline and oligomycin (that stimulate)] and its influence on LPL was also determined. Fasting augmented the activity of both AMPK and luminal LPL on immediate removal of hearts, effects that still remained even after in vitro perfusion of hearts for 1 h. Inhibition of AMPK in fasted hearts using an inhibitor like Ara-A or through provision of insulin markedly lowered the enhanced luminal LPL activity. In contrast, AMPK activators, like perhexiline and oligomycin, produced a significant elevation in heparin-releasable LPL activity. Thus, with fasting or drugs that influence AMPK, a strong correlation between this metabolic switch and cardiac LPL activity was established. Our data suggest that, in addition to its direct role in promoting FA oxidation, AMPK-mediated recruitment of LPL to the coronary lumen could represent an immediate compensatory response by the heart to guarantee FA supply.
Division of Pharmacology and Toxicology, Faculty of Pharmaceutical Sciences, The University of British Columbia, Vancouver, British Columbia, Canada.
Ding
D
An
Thomas
T
Pulinilkunnil
Dake
D
Qi
Sanjoy
S
Ghosh
Ashraf
A
Abrahani
Brian
B
Rodrigues
D000263:Adenylate Kinase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000818:Animals; D004734:Energy Metabolism / Q000502:physiology*; D005215:Fasting / Q000502:physiology; D005227:Fatty Acids / Q000378:metabolism; D006493:Heparin / Q000378:metabolism; D066298:In Vitro Techniques; D008071:Lipoprotein Lipase / Q000378:metabolism*; D008297:Male; D009206:Myocardium / Q000201:enzymology*; D010766:Phosphorylation; D051381:Rats; D017208:Rats, Wistar
D005227:Fatty Acids; D006493:Heparin; D000263:Adenylate Kinase; D008071:Lipoprotein Lipase