Novel GPIHBP1-independent pathway for clearance of plasma TGs in Angptl4 -/- Gpihbp1 -/- mice

Emily M Cushing; Kelli L Sylvers; Xun Chi; Shwetha K Shetty; Brandon S J Davies

doi:10.1194/jlr.M084749

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Novel GPIHBP1-independent pathway for clearance of plasma TGs in Angptl4 -/- Gpihbp1 -/- mice

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Novel GPIHBP1-independent pathway for clearance of plasma TGs in Angptl4 -/- Gpihbp1 -/- mice

Emily M Cushing, Kelli L Sylvers, Xun Chi, Shwetha K Shetty and Brandon S J Davies

Journal of lipid research, Vol.59(7), pp.1230-1243

07/2018

DOI: 10.1194/jlr.M084749

PMCID: PMC6027919

PMID: 29739862

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Abstract

Mice lacking glycosylphosphatidylinositol-anchored HDL-binding protein 1 (GPIHBP1) are unable to traffic LPL to the vascular lumen. Thus, triglyceride (TG) clearance is severely blunted, and mice are extremely hypertriglyceridemic. Paradoxically, mice lacking both GPIHBP1 and the LPL regulator, angiopoietin-like 4 (ANGPTL4), are far less hypertriglyceridemic. We sought to determine the mechanism by which double-knockout mice clear plasma TGs. We confirmed that, on a normal chow diet, plasma TG levels were lower in mice than in mice; however, the difference disappeared with administration of a high-fat diet. Although LPL remained mislocalized in double-knockout mice, plasma TG clearance in brown adipose tissue (BAT) increased compared with mice. Whole lipoprotein uptake was observed in the BAT of both and mice, but BAT lipase activity was significantly higher in the double-knockout mice. We conclude that mice clear plasma TGs primarily through a slow and noncanonical pathway that includes the uptake of whole lipoprotein particles.

lipoprotein lipase

lipase inhibition

lipoprotein metabolism

adipose tissue

glycosylphosphatidylinositol-anchored high density lipoprotein binding protein 1

triglycerides

lipolysis and fatty acid metabolism

chylomicrons

angiopoietin-like 4

Details

Title: Subtitle: Novel GPIHBP1-independent pathway for clearance of plasma TGs in Angptl4 -/- Gpihbp1 -/- mice
Creators: Emily M Cushing - Department of Biochemistry, Fraternal Order of Eagles Diabetes Research Center, and Obesity Research and Education Initiative, University of Iowa Carver College of Medicine, Iowa City, IA 52242
Kelli L Sylvers - Department of Biochemistry, Fraternal Order of Eagles Diabetes Research Center, and Obesity Research and Education Initiative, University of Iowa Carver College of Medicine, Iowa City, IA 52242
Xun Chi - Department of Biochemistry, Fraternal Order of Eagles Diabetes Research Center, and Obesity Research and Education Initiative, University of Iowa Carver College of Medicine, Iowa City, IA 52242
Shwetha K Shetty - Department of Biochemistry, Fraternal Order of Eagles Diabetes Research Center, and Obesity Research and Education Initiative, University of Iowa Carver College of Medicine, Iowa City, IA 52242
Brandon S J Davies - Department of Biochemistry, Fraternal Order of Eagles Diabetes Research Center, and Obesity Research and Education Initiative, University of Iowa Carver College of Medicine, Iowa City, IA 52242 Brandon-davies@uiowa.edu
Resource Type: Journal article
Publication Details: Journal of lipid research, Vol.59(7), pp.1230-1243
DOI: 10.1194/jlr.M084749
PMID: 29739862
PMCID: PMC6027919
NLM abbreviation: J Lipid Res
ISSN: 0022-2275
eISSN: 1539-7262
Publisher: United States
Grant note: R01 HL130146 / NHLBI NIH HHS T32 GM082729 / NIGMS NIH HHS
Language: English
Date published: 07/2018
Academic Unit: Fraternal Order of Eagles Diabetes Research Center; Biochemistry and Molecular Biology
Record Identifier: 9984025285502771

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