Lipoprotein Lipase and Its Regulators: An Unfolding Story
Lipoprotein lipase (LPL) is one of the most important factors in systemic lipid partitioning and metabolism. It mediates intravascular hydrolysis of triglycerides packed in lipoproteins such as chylomicrons and very-low-density lipoprotein (VLDL). Since its initial discovery in the 1940s, its biolog...
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Veröffentlicht in: | Trends in endocrinology and metabolism 2021-01, Vol.32 (1), p.48-61 |
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Zusammenfassung: | Lipoprotein lipase (LPL) is one of the most important factors in systemic lipid partitioning and metabolism. It mediates intravascular hydrolysis of triglycerides packed in lipoproteins such as chylomicrons and very-low-density lipoprotein (VLDL). Since its initial discovery in the 1940s, its biology and pathophysiological significance have been well characterized. Nonetheless, several studies in the past decade, with recent delineation of LPL crystal structure and the discovery of several new regulators such as angiopoietin-like proteins (ANGPTLs), glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1 (GPIHBP1), lipase maturation factor 1 (LMF1) and Sel-1 suppressor of Lin-12-like 1 (SEL1L), have completely transformed our understanding of LPL biology.
Lipoprotein lipase (LPL) is a central player in triglyceride metabolism by catalyzing intravascular triglyceride hydrolysis. Loss-of-function Lpl causes familial chylomicronemia syndrome in humans and mice.The functional unit of LPL was thought to be a dimer, but recent studies have demonstrated that it may be a monomer.Given its pathophysiological importance in lipid partitioning, the maturation and activity of LPL is tightly controlled.In the endoplasmic reticulum (ER), the maturation and folding of nascent LPL protein requires lipase maturation factor 1 (LMF1) and Sel-1 suppressor of Lin-12-like 1 (SEL1L); and in the post-ER compartments, the activity of LPL is inhibited by angiopoietin-like protein (ANGPTL)3, 4 and 8 in a tissue-specific manner; in the endothelial lumen, LPL is associated with glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1 (GPIHBP1) and regulated by various apolipoproteins. |
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ISSN: | 1043-2760 1879-3061 1879-3061 |
DOI: | 10.1016/j.tem.2020.11.005 |