脂肪酸移位酶CD36/SR-B2及其介导的长链脂肪酸跨膜转运
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摘要
长链脂肪酸是维持机体正常代谢的重要营养素,其吸收、转运和代谢对动物的健康、生长和生产具有重要意义。近年来,研究发现一些脂肪酸转运蛋白介导长链脂肪酸的跨膜转运。脂肪酸移位酶CD36/SR-B2是一种整合膜蛋白,能特异性介导脂肪酸在多种细胞中的跨膜转运。本文对CD36/SR-B2的由来、亚细胞定位、功能调控及其介导的长链脂肪酸跨膜转运进行概述,探讨其对脂质代谢的调控机制。
Long-chain fatty acids are important nutrients to maintain normal metabolism of the body,its absorption,transportation and metabolism have important influences on the health,growth and production of animals. In recent years,researchers have found that some fatty acid transporter proteins mediated the transportation of long-chain fatty acids across the membrane. The fatty acid translocase CD36/SR-B2 is an integrated membrane protein,which could specifically regulate the transmembrane transportation of fatty acids in many different types of cells. This paper reviewed the current understanding,subcellular localization,functional regulation of CD36/SR-B2 and the transmembrane transportation of long-chain fatty acids mediated by CD36/SRB2,and also discussed the regulation mechanism of lipid metabolism by CD36/SR-B2.[Chinese Journal of Animal Nutrition,2019,31( 6) : 2552-2559]
Long-chain fatty acids are important nutrients to maintain normal metabolism of the body,its absorption,transportation and metabolism have important influences on the health,growth and production of animals. In recent years,researchers have found that some fatty acid transporter proteins mediated the transportation of long-chain fatty acids across the membrane. The fatty acid translocase CD36/SR-B2 is an integrated membrane protein,which could specifically regulate the transmembrane transportation of fatty acids in many different types of cells. This paper reviewed the current understanding,subcellular localization,functional regulation of CD36/SR-B2 and the transmembrane transportation of long-chain fatty acids mediated by CD36/SRB2,and also discussed the regulation mechanism of lipid metabolism by CD36/SR-B2.[Chinese Journal of Animal Nutrition,2019,31( 6) : 2552-2559]
引文
[1]GLATZ J F C,LUIKEN J J F P.From fat to FAT(CD36/SR-B2):understanding the regulation of cellular fatty acid uptake[J].Biochimie,2017,136:21-26.
[2]KAZANTZIS M,STAHL A.Fatty acid transport proteins,implications in physiology and disease[J].Biochimica et Biophysica Acta:M olecular and Cell Biology of Lipids,2012,1821(5):852-857.
[3]ABUMRAD N A,EL-MAGHRABI M R,AMRI E Z,et al.Cloning of a rat adipocyte membrane protein implicated in binding or transport of long-chain fatty acids that is induced during preadipocyte differentiation.Homology w ith human CD36[J].Journal of Biological Chemistry,1993,268(24):17665-17668.
[4]GLATZ J F C,NABBEN M,HEATHER L C,et al.Regulation of the subcellular trafficking of CD36,a major determinant of cardiac fatty acid utilization[J].Biochimica et Biophysica Acta:M olecular and Cell Biology of Lipids,2016,1861(10):1461-1471.
[5]VAN NIEUWENHOVEN F A,LUIKEN J J F P,DEJONG Y F,et al.Stable transfection of fatty acid translocase(CD36)in a rat heart muscle cell line(H9c2)[J].Journal of Lipid Research,1998,39(10):2039-2047.
[6]FRANEKOVA V,ANGIN Y,HOEBERS N T H,et al.M arine omega-3 fatty acids prevent myocardial insulin resistance and metabolic remodeling as induced experimentally by high insulin exposure[J].American Journal of Physiology-Cell Physiology,2015,308(4):C297-C307.
[7]SMITH B K,JAIN S S,RIMBAUD S,et al.FAT/CD36 is located on the outer mitochondrial membrane,upstream of long-chain acyl-CoA synthetase,and regulates palmitate oxidation[J].Biochemical Journal,2011,437(1):125-134.
[8]石伯阳.牛乳腺上皮细胞转运蛋白的亚细胞定位及油酸转运研究[D].硕士学位论文.长沙:湖南农业大学,2014.
[9]MIKOSZ A,UKASZUK B,Z6)ENDZIAN-PI-OTROWSKA M,et al.Challenging of AS160/TBC1D4 alters intracellular lipid milieu in L6 myotubes incubated w ith palmitate[J].Journal of Cellular Physiology,2017,232(9):2373-2386.
[10]GLATZ J F C,LUIKEN J J F P.Fatty acids in cell signaling:historical perspective and future outlook[J].Prostaglandins,Leukotrienes and Essential Fatty Acids,2015,92:57-62.
[11]ADRIAN L,LENSKI M,TDTER K,et al.AMPKprevents palmitic acid-induced apoptosis and lipid accumulation in cardiomyocytes[J].Lipids,2017,52(9):737-750.
[12]CHANDA D,LUIKEN J J F P,GLATZ J F C.Signaling pathw ays involved in cardiac energy metabolism[J].FEBS Letters,2016,590(15):2364-2374.
[13]MIKOSZ A,UKASZUK B,Z6)ENDZIAN-PI-OTROWSKA M,et al.The effects of AS160 modulation on fatty acid transporters expression and lipid profile in L6 myotubes[J].Cellular Physiology and Biochemistry,2016,38(1):267-282.
[14]LUIKEN J J F P,CHANDA D,NABBEN M,et al.Post-translational modifications of CD36(SR-B2):implications for regulation of myocellular fatty acid uptake[J].Biochimica et Biophysica Acta:M olecular Basis of Disease,2016,1862(12):2253-2258.
[15]LACZY B,FLP N,ONAY-BESIKCI A,et al.A-cute regulation of cardiac metabolism by the hexosamine biosynthesis pathw ay and protein O-GlcNAcylation[J].PLoS One,2011,6(4):e18417.
[16]NEELS J G,GRIMALDI P A.Physiological functions of peroxisome proliferator-activated receptorβ[J].Physiological Review s,2014,94(3):795-858.
[17]YANG J,SAMBANDAM N,HAN X L,et al.CD36deficiency rescues lipotoxic cardiomyopathy[J].Circulation Research,2007,100(8):1208-1217.
[18]QIAO L P,ZOU C H,SHAO P,et al.Transcriptional regulation of fatty acid translocase/CD36 expression by CCAAT/enhancer-binding proteinα[J].Journal of Biological Chemistry,2008,283(14):8788-8795.
[19]MWAIKAMBO B R,YANG C,CHEMTOB S,et al.Hypoxia up-regulates CD36 expression and function via hypoxia-inducible factor-1-and phosphatidylinositol3-kinase-dependent mechanisms[J].Journal of Biological Chemistry,2009,284(39):26695-26707.
[20]MANSOR L S,DA LUZ SOUSA FIALHO M,YEAG,et al.Inhibition of sarcolemmal FAT/CD36 by sulfo-N-succinimidyl oleate rapidly corrects metabolism and restores function in the diabetic heart follow ing hypoxia/reoxygenation[J].Cardiovascular Research,2017,113(7):737-748.
[21]ZHANG P Z,GE Z J,WANG H D,et al.Prolactin improves hepatic steatosis via CD36 pathw ay[J].Journal of Hepatology,2018,68(6):1247-1255.
[22]BAATI N,FEILLET-COUDRAY C,FOURET G,et al.M yostatin deficiency is associated w ith lipidomic abnormalities in skeletal muscles[J].Biochimica et Biophysica Acta:M olecular and Cell Biology of Lipids,2017,1862(10):1044-1055.
[23]SUPRUNIUK E,MIKOSZ A,CHABOWSKI A,et al.The implication of PGC-1αon fatty acid transport across plasma and mitochondrial membranes in the insulin sensitive tissues[J].Frontiers in Physiology,2017,8:923.
[24]DA FONSECA F C P,DE BARROS MUCCI D,ASSUM PO R P,et al.Differential long-chain polyunsaturated fatty acids status and placental transport in adolescent pregnancies[J].Nutrients,2018,10(2):1-14.
[25]LI S S,WANG H C,WANG X X,et al.Betaine affects muscle lipid metabolism via regulating the fatty acid uptake and oxidation in finishing pig[J].Journal of Animal Science and Biotechnology,2017,8:72.
[26]ASTORINO T A,SCHUBERT M M.Changes in fat oxidation in response to various regimes of high intensity interval training(HIIT)[J].European Journal of Applied Physiology,2018,118(1):51-63.
[27]ROCHA-RODRIGUES S,RODRGUEZ A,BECER-RIL S,et al.Physical exercise remodels visceral adipose tissue and mitochondrial lipid metabolism in rats fed a high-fat diet[J].Clinical and Experimental Pharmacology and Physiology,2017,44(3):386-394.
[28]MANIO M C C,MATSUMURA S,MASUDA D,et al.CD36 is essential for endurance improvement,changes in w hole-body metabolism,and efficient PPAR-related transcriptional responses in the muscle w ith exercise training[J].Physiological Reports,2017,5(10):e13282.
[29]BONEN A,PAROLIN M L,STEINBERG G R,et al.Triacylglycerol accumulation in human obesity and type 2 diabetes is associated w ith increased rates of skeletal muscle fatty acid transport and increased sarcolemmal FAT/CD36[J].FASEB Journal,2004,18(10):1144-1146.
[30]GARBACZ W G,LU P P,MILLER T M,et al.Hepatic overexpression of CD36 improves glycogen homeostasis and attenuates high-fat diet-induced hepatic steatosis and insulin resistance[J].M olecular and Cellular Biology,2016,36(21):2715-2727.
[31]BONEN A,JAIN S S,SNOOK L A,et al.Extremely rapid increase in fatty acid transport and intramyocellular lipid accumulation but markedly delayed insulin resistance after high fat feeding in rats[J].Diabetologia,2015,58(10):2381-2391.
[32]STEINBUSCH L K M,WIJNEN W,SCHWENK RW,et al.Differential regulation of cardiac glucose and fatty acid uptake by endosomal pH and actin filaments[J].American Journal of Physiology-Cell Physiology,2010,298(6):C1549-C1559.
[2]KAZANTZIS M,STAHL A.Fatty acid transport proteins,implications in physiology and disease[J].Biochimica et Biophysica Acta:M olecular and Cell Biology of Lipids,2012,1821(5):852-857.
[3]ABUMRAD N A,EL-MAGHRABI M R,AMRI E Z,et al.Cloning of a rat adipocyte membrane protein implicated in binding or transport of long-chain fatty acids that is induced during preadipocyte differentiation.Homology w ith human CD36[J].Journal of Biological Chemistry,1993,268(24):17665-17668.
[4]GLATZ J F C,NABBEN M,HEATHER L C,et al.Regulation of the subcellular trafficking of CD36,a major determinant of cardiac fatty acid utilization[J].Biochimica et Biophysica Acta:M olecular and Cell Biology of Lipids,2016,1861(10):1461-1471.
[5]VAN NIEUWENHOVEN F A,LUIKEN J J F P,DEJONG Y F,et al.Stable transfection of fatty acid translocase(CD36)in a rat heart muscle cell line(H9c2)[J].Journal of Lipid Research,1998,39(10):2039-2047.
[6]FRANEKOVA V,ANGIN Y,HOEBERS N T H,et al.M arine omega-3 fatty acids prevent myocardial insulin resistance and metabolic remodeling as induced experimentally by high insulin exposure[J].American Journal of Physiology-Cell Physiology,2015,308(4):C297-C307.
[7]SMITH B K,JAIN S S,RIMBAUD S,et al.FAT/CD36 is located on the outer mitochondrial membrane,upstream of long-chain acyl-CoA synthetase,and regulates palmitate oxidation[J].Biochemical Journal,2011,437(1):125-134.
[8]石伯阳.牛乳腺上皮细胞转运蛋白的亚细胞定位及油酸转运研究[D].硕士学位论文.长沙:湖南农业大学,2014.
[9]MIKOSZ A,UKASZUK B,Z6)ENDZIAN-PI-OTROWSKA M,et al.Challenging of AS160/TBC1D4 alters intracellular lipid milieu in L6 myotubes incubated w ith palmitate[J].Journal of Cellular Physiology,2017,232(9):2373-2386.
[10]GLATZ J F C,LUIKEN J J F P.Fatty acids in cell signaling:historical perspective and future outlook[J].Prostaglandins,Leukotrienes and Essential Fatty Acids,2015,92:57-62.
[11]ADRIAN L,LENSKI M,TDTER K,et al.AMPKprevents palmitic acid-induced apoptosis and lipid accumulation in cardiomyocytes[J].Lipids,2017,52(9):737-750.
[12]CHANDA D,LUIKEN J J F P,GLATZ J F C.Signaling pathw ays involved in cardiac energy metabolism[J].FEBS Letters,2016,590(15):2364-2374.
[13]MIKOSZ A,UKASZUK B,Z6)ENDZIAN-PI-OTROWSKA M,et al.The effects of AS160 modulation on fatty acid transporters expression and lipid profile in L6 myotubes[J].Cellular Physiology and Biochemistry,2016,38(1):267-282.
[14]LUIKEN J J F P,CHANDA D,NABBEN M,et al.Post-translational modifications of CD36(SR-B2):implications for regulation of myocellular fatty acid uptake[J].Biochimica et Biophysica Acta:M olecular Basis of Disease,2016,1862(12):2253-2258.
[15]LACZY B,FLP N,ONAY-BESIKCI A,et al.A-cute regulation of cardiac metabolism by the hexosamine biosynthesis pathw ay and protein O-GlcNAcylation[J].PLoS One,2011,6(4):e18417.
[16]NEELS J G,GRIMALDI P A.Physiological functions of peroxisome proliferator-activated receptorβ[J].Physiological Review s,2014,94(3):795-858.
[17]YANG J,SAMBANDAM N,HAN X L,et al.CD36deficiency rescues lipotoxic cardiomyopathy[J].Circulation Research,2007,100(8):1208-1217.
[18]QIAO L P,ZOU C H,SHAO P,et al.Transcriptional regulation of fatty acid translocase/CD36 expression by CCAAT/enhancer-binding proteinα[J].Journal of Biological Chemistry,2008,283(14):8788-8795.
[19]MWAIKAMBO B R,YANG C,CHEMTOB S,et al.Hypoxia up-regulates CD36 expression and function via hypoxia-inducible factor-1-and phosphatidylinositol3-kinase-dependent mechanisms[J].Journal of Biological Chemistry,2009,284(39):26695-26707.
[20]MANSOR L S,DA LUZ SOUSA FIALHO M,YEAG,et al.Inhibition of sarcolemmal FAT/CD36 by sulfo-N-succinimidyl oleate rapidly corrects metabolism and restores function in the diabetic heart follow ing hypoxia/reoxygenation[J].Cardiovascular Research,2017,113(7):737-748.
[21]ZHANG P Z,GE Z J,WANG H D,et al.Prolactin improves hepatic steatosis via CD36 pathw ay[J].Journal of Hepatology,2018,68(6):1247-1255.
[22]BAATI N,FEILLET-COUDRAY C,FOURET G,et al.M yostatin deficiency is associated w ith lipidomic abnormalities in skeletal muscles[J].Biochimica et Biophysica Acta:M olecular and Cell Biology of Lipids,2017,1862(10):1044-1055.
[23]SUPRUNIUK E,MIKOSZ A,CHABOWSKI A,et al.The implication of PGC-1αon fatty acid transport across plasma and mitochondrial membranes in the insulin sensitive tissues[J].Frontiers in Physiology,2017,8:923.
[24]DA FONSECA F C P,DE BARROS MUCCI D,ASSUM PO R P,et al.Differential long-chain polyunsaturated fatty acids status and placental transport in adolescent pregnancies[J].Nutrients,2018,10(2):1-14.
[25]LI S S,WANG H C,WANG X X,et al.Betaine affects muscle lipid metabolism via regulating the fatty acid uptake and oxidation in finishing pig[J].Journal of Animal Science and Biotechnology,2017,8:72.
[26]ASTORINO T A,SCHUBERT M M.Changes in fat oxidation in response to various regimes of high intensity interval training(HIIT)[J].European Journal of Applied Physiology,2018,118(1):51-63.
[27]ROCHA-RODRIGUES S,RODRGUEZ A,BECER-RIL S,et al.Physical exercise remodels visceral adipose tissue and mitochondrial lipid metabolism in rats fed a high-fat diet[J].Clinical and Experimental Pharmacology and Physiology,2017,44(3):386-394.
[28]MANIO M C C,MATSUMURA S,MASUDA D,et al.CD36 is essential for endurance improvement,changes in w hole-body metabolism,and efficient PPAR-related transcriptional responses in the muscle w ith exercise training[J].Physiological Reports,2017,5(10):e13282.
[29]BONEN A,PAROLIN M L,STEINBERG G R,et al.Triacylglycerol accumulation in human obesity and type 2 diabetes is associated w ith increased rates of skeletal muscle fatty acid transport and increased sarcolemmal FAT/CD36[J].FASEB Journal,2004,18(10):1144-1146.
[30]GARBACZ W G,LU P P,MILLER T M,et al.Hepatic overexpression of CD36 improves glycogen homeostasis and attenuates high-fat diet-induced hepatic steatosis and insulin resistance[J].M olecular and Cellular Biology,2016,36(21):2715-2727.
[31]BONEN A,JAIN S S,SNOOK L A,et al.Extremely rapid increase in fatty acid transport and intramyocellular lipid accumulation but markedly delayed insulin resistance after high fat feeding in rats[J].Diabetologia,2015,58(10):2381-2391.
[32]STEINBUSCH L K M,WIJNEN W,SCHWENK RW,et al.Differential regulation of cardiac glucose and fatty acid uptake by endosomal pH and actin filaments[J].American Journal of Physiology-Cell Physiology,2010,298(6):C1549-C1559.