title: Acute intralipid infusion reduces cardiac luminal lipoprotein lipase but recruits additional enzyme from cardiomyocytes.
abstract: OBJECTIVE
  Lipoprotein lipase (LPL) metabolizes the triglyceride (TG) core of lipoproteins. We evaluated whether circulating lipids can regulate LPL by influencing the transfer of enzyme from the myocyte to the endothelial lumen.
  
  
  METHODS
  Acute intralipid (IL, 10% and 20%) infusion was performed in male Wistar rats. After 3 h, insulin resistance was assessed using a euglycemic hyperinsulinemic clamp. Cardiac LPL activity was determined by retrogradely perfusing the hearts with heparin. Immunogold electron microscopy visualized LPL, and heparanase was detected by immunofluorescence. Cardiac myocytes were also isolated, and heparin-releasable LPL activity was measured.
  
  
  RESULTS
  IL infusion increased both plasma and cardiac lipids. Circulating basal plasma LPL activity increased for the duration of the infusion. Compared to control (CON) hearts, there was a substantial decrease in heparin-releasable LPL activity at the vascular lumen following 3 h of IL infusion, an effect unrelated to changes in gene and protein expression or whole-body insulin resistance. Although constant perfusion of CON hearts with heparin stripped off most of the luminal bound LPL, hearts from IL-infused animals continued to release excessive amounts of the enzyme, suggesting buildup of LPL within endothelial cells or at the endothelial basolateral surface. Immunogold labeling confirmed this observation and demonstrated robust anti-LPL staining at these sites, only in IL hearts. Perfusing hearts from IL-rats in vitro, in the absence of TG, allowed the accumulated enzyme pool to transfer to the coronary lumen.
  
  
  CONCLUSIONS
  Our data suggest that acute amplification of lipids reduces cardiac luminal LPL but facilitates additional recruitment of cardiomyocyte enzyme. Should this mechanism occur globally, it could contribute towards management of hyperlipidemia.
authors.affiliation: Division of Pharmacology and Toxicology, Faculty of Pharmaceutical Sciences, The University of British Columbia, 2146 East Mall, Vancouver, BC, Canada V6T 1Z3.
authors.forename: Dake
authors.initials: D
authors.lastname: Qi
authors.forename: Kuo-Hsing
authors.initials: KH
authors.lastname: Kuo
authors.forename: Ashraf
authors.initials: A
authors.lastname: Abrahani
authors.forename: Ding
authors.initials: D
authors.lastname: An
authors.forename: Yadan
authors.initials: Y
authors.lastname: Qi
authors.forename: Jessica
authors.initials: J
authors.lastname: Heung
authors.forename: Girish
authors.initials: G
authors.lastname: Kewalramani
authors.forename: Thomas
authors.initials: T
authors.lastname: Pulinilkunnil
authors.forename: Sanjoy
authors.initials: S
authors.lastname: Ghosh
authors.forename: Sheila M
authors.initials: SM
authors.lastname: Innis
authors.forename: Brian
authors.initials: B
authors.lastname: Rodrigues
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D005227:Fatty Acids / Q000032:analysis / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D015870:Gene Expression; D005947:Glucose / Q000494:pharmacology; D005966:Glucuronidase / Q000032:analysis / Q000378:metabolism; D006493:Heparin / Q000378:metabolism; D007262:Infusions, Intravenous; D007328:Insulin / Q000494:pharmacology; D007333:Insulin Resistance; D008055:Lipids / Q000008:administration & dosage* / Q000032:analysis / Q000097:blood; D008071:Lipoprotein Lipase / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D008297:Male; D016253:Microscopy, Immunoelectron; D009206:Myocardium / Q000737:chemistry / Q000201:enzymology*; D032383:Myocytes, Cardiac / Q000201:enzymology; D010477:Perfusion; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014280:Triglycerides / Q000032:analysis / Q000378:metabolism; D000099175:Heparanase
chemical_list: D005227:Fatty Acids; D005947:Glucose; D005966:Glucuronidase; D006493:Heparin; D007328:Insulin; D008055:Lipids; D008071:Lipoprotein Lipase; D014280:Triglycerides; D000099175:Heparanase