title: Intrinsic and extrinsic regulation of cardiac lipoprotein lipase following diabetes.
abstract: Cardiac lipoprotein lipase (LPL) is a pivotal enzyme controlling heart metabolism by providing the majority of fatty acids required by this organ. From activation in cardiomyocytes to secretion to the vascular lumen, cardiac LPL is regulated by multiple pathways, which are altered during diabetes. Hence, dimerization/activation of LPL is modified following diabetes, a process controlled by lipase maturation factor 1. The role of AMP-activated protein kinase, protein kinase D, and heparan sulfate proteoglycans, intrinsic factors that regulate the intracellular transport of LPL is also shifted, and is discussed. More recent studies have identified several exogenous factors released from endothelial cells (EC) and adipose tissue that are required for proper functioning of LPL. In response to hyperglycemia, both active and latent heparanase are released from EC to facilitate LPL secretion. Diabetes also increased the expression of glycosylphosphatidylinositol-anchored high density lipoprotein-binding protein 1 (GPIHBP1) in EC, which mediates the transport of LPL across EC. Angiopoietin-like protein 4 secreted from the adipose tissue has the potential to reduce coronary LPL activity. Knowledge of these intrinsic and extrinsic factors could be used develop therapeutic targets to normalize LPL function, and maintain cardiac energy homeostasis after diabetes.
authors.affiliation: Faculty of Pharmaceutical Sciences, The University of British Columbia, 2405 Wesbrook Mall, Vancouver, BC V6T 1Z3, Canada.
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Faculty of Pharmaceutical Sciences, The University of British Columbia, 2405 Wesbrook Mall, Vancouver, BC V6T 1Z3, Canada. Electronic address: rodrigue@mail.ubc.ca.
authors.forename: Brian
authors.initials: B
authors.lastname: Rodrigues
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D003920:Diabetes Mellitus / Q000097:blood / Q000201:enzymology* / Q000235:genetics; D058065:Diabetic Cardiomyopathies / Q000097:blood / Q000201:enzymology* / Q000235:genetics; D042783:Endothelial Cells / Q000378:metabolism; D004734:Energy Metabolism; D004789:Enzyme Activation; D005227:Fatty Acids / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D008071:Lipoprotein Lipase / Q000235:genetics / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000201:enzymology*; D015398:Signal Transduction
chemical_list: D001786:Blood Glucose; D005227:Fatty Acids; C548261:LPL protein, human; D008071:Lipoprotein Lipase
keywords: Cardiomyocytes; Diabetes; Endothelial cells; Heart metabolism; Lipoprotein lipase; Post-translational regulation