New Wrinkles in Lipoprotein Lipase Biology

Overview

Journal Curr Opin Lipidol

Specialty Biochemistry

Date 2011 Nov 30

PMID 22123668

Citations 27

Authors

Brandon S J Davies

Anne P Beigneux

Loren G Fong

Stephen G Young

Affiliations

Soon will be listed here.

Abstract

Purpose Of Review: We summarize recent progress on GPIHBP1, a molecule that transports lipoprotein lipase (LPL) to the capillary lumen, and discuss several newly studied molecules that appear important for the regulation of LPL activity.

Recent Findings: LPL, the enzyme responsible for the lipolytic processing of triglyceride-rich lipoproteins, interacts with multiple proteins and is regulated at multiple levels. Several regulators of LPL activity have been known for years and have been investigated thoroughly, but several have been identified only recently, including an endothelial cell protein that transports LPL to the capillary lumen, a microRNA that reduces LPL transcript levels, a sorting protein that targets LPL for uptake and degradation, and a transcription factor that increases the expression of apolipoproteins that regulate LPL activity.

Summary: Proper regulation of LPL is important for controlling the delivery of lipid nutrients to tissues. Recent studies have identified GPIHBP1 as the molecule that transports LPL to the capillary lumen, and have also identified other molecules that are potentially important for regulating LPL activity. These new discoveries open new doors for understanding basic mechanisms of lipolysis and hyperlipidemia.

Citing Articles

A unified model for regulating lipoprotein lipase activity.

Zhang R, Zhang K Trends Endocrinol Metab. 2024; 35(6):490-504.

PMID: 38521668 PMC: 11663433. DOI: 10.1016/j.tem.2024.02.016.

FOS Inhibits the Differentiation of Intramuscular Adipocytes in Goats.

Hu T, Li Z, Gong C, Xiong Y, Sun S, Xing J Genes (Basel). 2023; 14(11).

PMID: 38003034 PMC: 10671551. DOI: 10.3390/genes14112088.

Analysis of key genes and pathways in breast ductal carcinoma .

Wu M, Zhao H Oncol Lett. 2020; 20(5):217.

PMID: 32963623 PMC: 7491034. DOI: 10.3892/ol.2020.12080.

Syndecan-1 Mediates Sorting of Soluble Lipoprotein Lipase with Sphingomyelin-Rich Membrane in the Golgi Apparatus.

Sundberg E, Deng Y, Burd C Dev Cell. 2019; 51(3):387-398.e4.

PMID: 31543446 PMC: 6832887. DOI: 10.1016/j.devcel.2019.08.014.

Lipoprotein lipase regulates hematopoietic stem progenitor cell maintenance through DHA supply.

Liu C, Han T, Stachura D, Wang H, Vaisman B, Kim J Nat Commun. 2018; 9(1):1310.

PMID: 29615667 PMC: 5882990. DOI: 10.1038/s41467-018-03775-y.

References

Coca-Prieto I, Kroupa O, Gonzalez-Santos P, Magne J, Olivecrona G, Ehrenborg E . Childhood-onset chylomicronaemia with reduced plasma lipoprotein lipase activity and mass: identification of a novel GPIHBP1 mutation. J Intern Med. 2011; 270(3):224-8. DOI: 10.1111/j.1365-2796.2011.02361.x. View

McConathy W, Alaupovic P . Studies on the isolation and partial characterization of apolipoprotein D and lipoprotein D of human plasma. Biochemistry. 1976; 15(3):515-20. DOI: 10.1021/bi00648a010. View

Calandra S, Priore Oliva C, Tarugi P, Bertolini S . APOA5 and triglyceride metabolism, lesson from human APOA5 deficiency. Curr Opin Lipidol. 2006; 17(2):122-7. DOI: 10.1097/01.mol.0000217892.00618.54. View

Sambandam N, Abrahani M, St Pierre E, Cam M, Rodrigues B . Localization of lipoprotein lipase in the diabetic heart: regulation by acute changes in insulin. Arterioscler Thromb Vasc Biol. 1999; 19(6):1526-34. DOI: 10.1161/01.atv.19.6.1526. View

Lee J, Giannikopoulos P, Duncan S, Wang J, Johansen C, Brown J . The transcription factor cyclic AMP-responsive element-binding protein H regulates triglyceride metabolism. Nat Med. 2011; 17(7):812-5. PMC: 3374483. DOI: 10.1038/nm.2347. View

Pennacchio L, Olivier M, Hubacek J, Cohen J, Cox D, Fruchart J . An apolipoprotein influencing triglycerides in humans and mice revealed by comparative sequencing. Science. 2001; 294(5540):169-73. DOI: 10.1126/science.1064852. View

Grosskopf I, Baroukh N, Lee S, Kamari Y, Harats D, Rubin E . Apolipoprotein A-V deficiency results in marked hypertriglyceridemia attributable to decreased lipolysis of triglyceride-rich lipoproteins and removal of their remnants. Arterioscler Thromb Vasc Biol. 2005; 25(12):2573-9. DOI: 10.1161/01.ATV.0000186189.26141.12. View

Wang H, Astarita G, Taussig M, Bharadwaj K, DiPatrizio N, Nave K . Deficiency of lipoprotein lipase in neurons modifies the regulation of energy balance and leads to obesity. Cell Metab. 2011; 13(1):105-13. PMC: 3034302. DOI: 10.1016/j.cmet.2010.12.006. View

Beigneux A, Davies B, Tat S, Chen J, Gin P, Voss C . Assessing the role of the glycosylphosphatidylinositol-anchored high density lipoprotein-binding protein 1 (GPIHBP1) three-finger domain in binding lipoprotein lipase. J Biol Chem. 2011; 286(22):19735-43. PMC: 3103352. DOI: 10.1074/jbc.M111.242024. View

10.

Doolittle M, Singh N, Chang C, Schotz M . Synthesis and regulation of lipoprotein lipase in the hippocampus. J Lipid Res. 1990; 31(7):1307-13. View

11.

Desai P, Bunker C, Ukoli F, Kamboh M . Genetic variation in the apolipoprotein D gene among African blacks and its significance in lipid metabolism. Atherosclerosis. 2002; 163(2):329-38. DOI: 10.1016/s0021-9150(02)00012-6. View

12.

Henderson H, Leisegang F, Hassan F, Hayden M, Marais D . A novel Glu421Lys substitution in the lipoprotein lipase gene in pregnancy-induced hypertriglyceridemic pancreatitis. Clin Chim Acta. 1998; 269(1):1-12. DOI: 10.1016/s0009-8981(97)00144-7. View

13.

Tan M, Sata T, HAVEL R . The significance of lipoprotein lipase in rat skeletal muscles. J Lipid Res. 1977; 18(3):363-70. View

14.

Kinnunen P, Jackson R, Smith L, Gotto Jr A, Sparrow J . Activation of lipoprotein lipase by native and synthetic fragments of human plasma apolipoprotein C-II. Proc Natl Acad Sci U S A. 1977; 74(11):4848-51. PMC: 432053. DOI: 10.1073/pnas.74.11.4848. View

15.

Weinstein M, Yin L, Beigneux A, Davies B, Gin P, Estrada K . Abnormal patterns of lipoprotein lipase release into the plasma in GPIHBP1-deficient mice. J Biol Chem. 2008; 283(50):34511-8. PMC: 2596386. DOI: 10.1074/jbc.M806067200. View

16.

Vilaro S, Camps L, Reina M, Perez-Clausell J, Llobera M, Olivecrona T . Localization of lipoprotein lipase to discrete areas of the guinea pig brain. Brain Res. 1990; 506(2):249-53. DOI: 10.1016/0006-8993(90)91258-i. View

17.

Wang J, Hegele R . Homozygous missense mutation (G56R) in glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1 (GPI-HBP1) in two siblings with fasting chylomicronemia (MIM 144650). Lipids Health Dis. 2007; 6:23. PMC: 2039732. DOI: 10.1186/1476-511X-6-23. View

18.

Chen T, Li Z, Tu J, Zhu W, Ge J, Zheng X . MicroRNA-29a regulates pro-inflammatory cytokine secretion and scavenger receptor expression by targeting LPL in oxLDL-stimulated dendritic cells. FEBS Lett. 2011; 585(4):657-63. DOI: 10.1016/j.febslet.2011.01.027. View

19.

Beigneux A, Franssen R, Bensadoun A, Gin P, Melford K, Peter J . Chylomicronemia with a mutant GPIHBP1 (Q115P) that cannot bind lipoprotein lipase. Arterioscler Thromb Vasc Biol. 2009; 29(6):956-62. PMC: 2811263. DOI: 10.1161/ATVBAHA.109.186577. View

20.

Ginsberg H, Le N, Goldberg I, Gibson J, Rubinstein A, Norum R . Apolipoprotein B metabolism in subjects with deficiency of apolipoproteins CIII and AI. Evidence that apolipoprotein CIII inhibits catabolism of triglyceride-rich lipoproteins by lipoprotein lipase in vivo. J Clin Invest. 1986; 78(5):1287-95. PMC: 423815. DOI: 10.1172/JCI112713. View