Does long-term metformin treatment increase cardiac lipoprotein lipase?
Abstract
Acute activation of adenosine monophosphate-activated protein kinase (AMPK) or jumps in cardiac work increased cardiac endothelial lipoprotein lipase (LPL), yet it is unclear whether chronic AMPK activation maintains this elevated LPL. To activate AMPK chronically, metformin at low (300 mg/kg/d) and high dose (600 mg/kg/d) was administered in drinking water for 14 days. Control, metformin-treated, and 5-amino-imidazole-4-carboxamide riboside (AICAR)-treated (0.5 mmol/L) ex vivo hearts were perfused to investigate uptake of triacylglycerol and cardiac LPL activity. For perfused rat hearts, increased uptake of labeled Intralipid and β-oxidation of Intralipid-fatty acid were noted for both AICAR (P < .05) and high-dose metformin (P < .01). Intralipid incorporation into tissue lipids was decreased by AICAR (P < .05) and increased after high-dose metformin (P < .05), the increase manifest as enhanced triacylglycerol deposition (P < .05). Low-dose metformin did not alter lipid uptake or tissue deposition. Both high-dose metformin and AICAR decreased cardiac acetyl-coenzyme A carboxylase activity (P < .01). Heparin-releasable LPL was increased after treatment with AICAR (P < .05) and high-dose metformin (P < .01). Low-dose metformin did not alter cardiac LPL. High-dose metformin doubled immunoreactive AMPK and phospho-AMPK protein (P < .001) and increased phosphorylation of p38-mitogen-activated protein kinase (P < .05). After heparin pretreatment, the rate of recruitment of LPL to…
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