Regulation of Fatty Acid Uptake into Tissues: Lipoprotein Lipase- and CD36-mediated Pathways

Overview

Journal J Lipid Res

Publisher Elsevier

Specialty Biochemistry

Date 2008 Nov 27

PMID 19033209

Citations 191

Authors

Ira J Goldberg

Robert H Eckel

Nada A Abumrad

Affiliations

Soon will be listed here.

Abstract

Cells obtain FAs either from LPL-catalyzed hydrolysis of lipoprotein triglyceride or from unesterified FFAs associated with albumin. LPL also influences uptake of esterified lipids such as cholesteryl and retinyl esters that are not hydrolyzed in the plasma. This process might not involve LPL enzymatic activity. LPL is regulated by feeding/fasting, insulin, and exercise. Although a number of molecules may affect cellular uptake of FFAs, the best characterized is CD36. Genetic deletion of this multiligand receptor reduces FFA uptake into skeletal muscle, heart, and adipose tissue, and impairs intestinal chylomicron production and clearance of lipoproteins from the blood. CD36 is regulated by some of the same factors that regulate LPL, including insulin, muscle contraction, and fasting, in part, via ubiquitination. LPL and CD36 actions in various tissues coordinate biodistribution of fat-derived calories.

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References

Goudriaan J, den Boer M, Rensen P, Febbraio M, Kuipers F, Romijn J . CD36 deficiency in mice impairs lipoprotein lipase-mediated triglyceride clearance. J Lipid Res. 2005; 46(10):2175-81. DOI: 10.1194/jlr.M500112-JLR200. View

Abumrad N, Harmon C, Ibrahimi A . Membrane transport of long-chain fatty acids: evidence for a facilitated process. J Lipid Res. 1998; 39(12):2309-18. View

Kratky D, Zimmermann R, Wagner E, Strauss J, Jin W, Kostner G . Endothelial lipase provides an alternative pathway for FFA uptake in lipoprotein lipase-deficient mouse adipose tissue. J Clin Invest. 2005; 115(1):161-7. PMC: 539186. DOI: 10.1172/JCI15972. View

Sattler W, Levak-Frank S, Radner H, Kostner G, Zechner R . Muscle-specific overexpression of lipoprotein lipase in transgenic mice results in increased alpha-tocopherol levels in skeletal muscle. Biochem J. 1996; 318 ( Pt 1):15-9. PMC: 1217581. DOI: 10.1042/bj3180015. View

Greenwood M . The relationship of enzyme activity to feeding behavior in rats: lipoprotein lipase as the metabolic gatekeeper. Int J Obes. 1985; 9 Suppl 1:67-70. View

Hajri T, Hall A, Jensen D, Pietka T, Drover V, Tao H . CD36-facilitated fatty acid uptake inhibits leptin production and signaling in adipose tissue. Diabetes. 2007; 56(7):1872-80. DOI: 10.2337/db06-1699. View

Sukonina V, Lookene A, Olivecrona T, Olivecrona G . Angiopoietin-like protein 4 converts lipoprotein lipase to inactive monomers and modulates lipase activity in adipose tissue. Proc Natl Acad Sci U S A. 2006; 103(46):17450-5. PMC: 1859949. DOI: 10.1073/pnas.0604026103. View

Augustus A, Yagyu H, Haemmerle G, Bensadoun A, Vikramadithyan R, Park S . Cardiac-specific knock-out of lipoprotein lipase alters plasma lipoprotein triglyceride metabolism and cardiac gene expression. J Biol Chem. 2004; 279(24):25050-7. DOI: 10.1074/jbc.M401028200. View

Merkel M, Weinstock P, Chajek-Shaul T, Radner H, Yin B, Breslow J . Lipoprotein lipase expression exclusively in liver. A mouse model for metabolism in the neonatal period and during cachexia. J Clin Invest. 1998; 102(5):893-901. PMC: 508954. DOI: 10.1172/JCI2912. View

10.

Berk P, Stump D . Mechanisms of cellular uptake of long chain free fatty acids. Mol Cell Biochem. 1999; 192(1-2):17-31. View

11.

ZILVERSMIT D . A proposal linking atherogenesis to the interaction of endothelial lipoprotein lipase with triglyceride-rich lipoproteins. Circ Res. 1973; 33(6):633-8. DOI: 10.1161/01.res.33.6.633. View

12.

Nassir F, Wilson B, Han X, Gross R, Abumrad N . CD36 is important for fatty acid and cholesterol uptake by the proximal but not distal intestine. J Biol Chem. 2007; 282(27):19493-501. DOI: 10.1074/jbc.M703330200. View

13.

Yamashita S, Hirano K, Kuwasako T, Janabi M, Toyama Y, Ishigami M . Physiological and pathological roles of a multi-ligand receptor CD36 in atherogenesis; insights from CD36-deficient patients. Mol Cell Biochem. 2006; 299(1-2):19-22. DOI: 10.1007/s11010-005-9031-4. View

14.

Wu G, Zhang L, Gupta J, Olivecrona G, Olivecrona T . A transcription-dependent mechanism, akin to that in adipose tissue, modulates lipoprotein lipase activity in rat heart. Am J Physiol Endocrinol Metab. 2007; 293(4):E908-15. DOI: 10.1152/ajpendo.00634.2006. View

15.

Babaev V, Fazio S, Gleaves L, Carter K, Semenkovich C, Linton M . Macrophage lipoprotein lipase promotes foam cell formation and atherosclerosis in vivo. J Clin Invest. 1999; 103(12):1697-705. PMC: 408384. DOI: 10.1172/JCI6117. View

16.

MacArthur J, Bishop J, Stanford K, Wang L, Bensadoun A, Witztum J . Liver heparan sulfate proteoglycans mediate clearance of triglyceride-rich lipoproteins independently of LDL receptor family members. J Clin Invest. 2007; 117(1):153-64. PMC: 1716206. DOI: 10.1172/JCI29154. View

17.

Miranda M, Sorkin A . Regulation of receptors and transporters by ubiquitination: new insights into surprisingly similar mechanisms. Mol Interv. 2007; 7(3):157-67. DOI: 10.1124/mi.7.3.7. View

18.

Chawla A, Lee C, Barak Y, He W, Rosenfeld J, Liao D . PPARdelta is a very low-density lipoprotein sensor in macrophages. Proc Natl Acad Sci U S A. 2003; 100(3):1268-73. PMC: 298762. DOI: 10.1073/pnas.0337331100. View

19.

Merkel M, Heeren J, Dudeck W, Rinninger F, Radner H, Breslow J . Inactive lipoprotein lipase (LPL) alone increases selective cholesterol ester uptake in vivo, whereas in the presence of active LPL it also increases triglyceride hydrolysis and whole particle lipoprotein uptake. J Biol Chem. 2001; 277(9):7405-11. DOI: 10.1074/jbc.M107914200. View

20.

Yost T, JENSEN D, Haugen B, Eckel R . Effect of dietary macronutrient composition on tissue-specific lipoprotein lipase activity and insulin action in normal-weight subjects. Am J Clin Nutr. 1998; 68(2):296-302. DOI: 10.1093/ajcn/68.2.296. View