Transgenic expression and genetic variation of Lmf1 affect LPL activity in mice and humans.

Arteriosclerosis, Thrombosis, and Vascular Biology
M HosseiniMiklós Péterfy

Abstract

Lipoprotein lipase (LPL) is a principal enzyme in lipoprotein metabolism, tissue lipid utilization, and energy metabolism. LPL is synthesized by parenchymal cells in adipose, heart, and muscle tissues followed by secretion to extracellular sites, where lipolyic function is exerted. The catalytic activity of LPL is attained during posttranslational maturation, which involves glycosylation, folding, and subunit assembly within the endoplasmic reticulum. A lipase-chaperone, lipase maturation factor 1 (Lmf1), has recently emerged as a critical factor in this process. Previous studies demonstrated that loss-of-function mutations of Lmf1 result in diminished lipase activity and severe hypertriglyceridemia in mice and human subjects. The objective of this study is to investigate whether, beyond its role as a required factor in lipase maturation, variation in Lmf1 expression is sufficient to modulate LPL activity in vivo. To assess the effects of Lmf1 overexpression in adipose and muscle tissues, we generated aP2-Lmf1 and Mck-Lmf1 transgenic mice. Characterization of relevant tissues revealed increased LPL activity in both mouse strains. In the omental and subcutaneous adipose depots, Lmf1 overexpression was associated with increased L...Continue Reading

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Citations

Mar 19, 2015·The Journal of Biological Chemistry·R Grace WaltonBrian S Finlin
Oct 4, 2017·Lipids in Health and Disease·Wenjing WuJin Zhang
Aug 28, 2020·Frontiers in Endocrinology·Debapriya Basu, Karin E Bornfeldt
Sep 29, 2021·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Hao LiWeiping J Zhang

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