王红芳 杨维仁* 刘建新 杨在宾

（1.山东农业大学动物科技学院,泰安271018;2.浙江大学动物科技学院奶业科学研究所,杭州 310029）

在动物体内,脂类物质有着多重复杂的功能,例如作为能源物质、细胞膜的组分等。动物产品中的脂类物质与人类健康又有着密切的关系,例如乳脂成分和含量影响着乳制品的品质,进而影响人类健康。近年来研究表明,动物体内的脂类物质在动物体内的合成过程均受到固醇调控元件结合蛋白（sterol-regulation element binding proteins, SREBPs）的调控[1]。SREBPs能激活参与脂类（固醇类、脂肪酸、甘油三酯等）合成一连串酶的转录[2],是公认的脂类物质合成的关键调节因子。本文针对SREBPs的结构功能、组织分布、合成调节以及其对乳脂合成的调节进行全面综述。

1 SREBPs的结构、功能与组织分布

1.1 SREBPs的结构

SREBPs是调控胆固醇和脂肪酸合成及体内平衡的膜锚定转录因子[3-4],属于螺旋-环螺旋亮氨酸拉链家族（basic helix-loop-helix-leucine zip-per fam ily,bHLH-LZ）[5]。SREBPs的无活性前体蛋白结合于内质网膜上,约由1 150个氨基酸组成。整个蛋白质分为3个结构域:1）N端480个氨基酸区域,内包含转录激活区、富含丝氨酸和脯氨酸区、bHLH-LZ区;2）2个伸入到内质网内腔的疏水跨膜片段,这2个跨膜片段之间被一个约30个氨基酸大小的短环隔开;3）羧基端约590个氨基酸的区域,该区域是主要的调节区域,并且在羧基端形成了一个复杂的、能紧密结合于SREBPs裂解激活蛋白（SREBPs-cleacage-activating protein,SCAP）的区域,起到固醇感受器的作用[6-7]。目前发现,SREBPs由2个基因编码合成3个亚型SREBP-1a、SREBP-1c和SREBP-2,其中SREBP-1a和SREBP-1c来源于同一个基因SREBP-1,由于转录的起始位点不同使得SREBP-1a比SREBP-1c少了一段氨基酸序列,而SREBP-2亚型来源于单独的基因SREBP-2基因[8],与SREBP-1基因拥有45%的同源序列[9]。

1.2 SREBPs的功能与组织分布

SREBPs的3个亚型具有不同转录激活作用。SREBP-1c主要调节脂肪酸合成和胰岛素介导的葡萄糖代谢,尤其是脂肪形成;而SREBP-2主要与胆固醇代谢密切相关;SREBP-1a兼备了上述二者的作用[4]。SREBP-1a的转录激活作用比SREBP-1c要强,主要是因为它的N端转录激活区域较长[10]。上述三者除了作用不同外,在组织内的分布也有明显的区别,在人和小鼠等哺乳动物体内,SREBP-1c是优势表达的亚型,尤其是在肝脏、白色脂肪组织、骨骼肌、肾上腺和大脑中含量比较高,而SREBP-1a主要在体外培养的细胞系或者是细胞增殖程度高的组织中表达,例如脾脏和肠[11]。

2 SREBPs合成的调节

SREBPs合成的调节可以在不同的水平进行,包括转录水平和转录后水平的调节。

2.1 SREBPs在转录水平的调节

影响SREBPs转录调节的因素很多,机制也相当复杂,包括动物的营养水平、个别营养因子、激素、核激素受体和某些酶类等,这些因子相互制约和影响,形成了一个庞大、复杂、灵活、多变的SREBPs转录调节网络。

在啮齿动物的禁食后重新给饲的试验中,人们首次发现SREBP-1c的转录是可以调节的,给小鼠禁食后,小鼠的肝脏[12]、白色脂肪组织[13]和骨骼肌[14-15]中SREBP-1c的m RNA丰度明显减少,说明动物营养水平的高低可以调节SREBP-1c转录。但是对SREBPs的其他亚型没有明显影响。

有试验证明胰岛素能诱导SREBP-1c的转录。例如,在离体的脂肪细胞[13]、肝细胞[16]中加入胰岛素,发现SREBP-1c的转录上调,在人体的脂肪组织和肌肉中也有类似发现[17-18]。将糖尿病小鼠与正常小鼠相比较,SREBP-1c的转录活性降低,注入胰岛素后,SREBP-1c的转录会明显上调[19]。由此可见,不论是离体细胞还是活体动物中,胰岛素都有诱导SREBP-1c转录的作用。其效应途径可能是通过3-磷脂酰肌醇激酶[phosphatidy l inositol 3 kinase,PI（3）-K]来实现的[20-21],并且有资料显示其下游作用元件可能是蛋白激酶B（protein kinase B, PKB）和蛋白激酶C（protein kinase C, PKC）[21-24]。

肝脏X受体α（liver X receptorα,LXRα）是一种核激素受体,它可以被氧化固醇激活（胆固醇的衍生物）,激活的LXRα可以诱导SREBP-1c的转录。有研究证明,缺乏LXRα的动物,SREBP-1c呈现出了较低的基因表达量,但是肝脏X受体β（liver X receptorβ,LXRβ）基因的敲除,却对SREBP-1c的转录无影响[25-26]。饲喂动物高胆固醇饲粮或者是LXRα促效药都能激活LXRα,从而促进SREBP-1c的转录[26-28],有人曾提出,LXRα诱导SREBP-1c转录是为了使其进一步诱导脂肪酸的合成,能使得更多的脂肪酸和游离的胆固醇结合生成胆固醇酯,使过高的胆固醇浓度得到缓解[29]。LXRα也可以直接诱导个别脂肪酸生成基因的转录,例如脂肪酸合成酶（fat acid synthetase,FAS）[30]、乙酰辅酶A羧化酶（acetyl CoA carboxylase,ACC）[31]。但是饲喂SREBP-1c基因无效的小鼠（SREBP-1c null mice）LXRα促效药却不能有效促进脂肪酸合成[32],这说明SREBP-1c是LXRα诱导脂肪酸合成的必要中间元件。

也有资料显示雄性激素和孕酮能诱导SREBP-1c的转录[33-35],但机理尚无报道,一般认为这些激素有诱导脂肪合成的作用,而SREBP-1c被认为是这一诱导过程中的中间调节物。

此外,一磷酸腺苷活化蛋白激酶（AM P-activated protein kinase,AMPK）对SREBP-1c的转录有抑制作用[36]。AMPK是一种催化AMP生成ATP的酶,通常在动物体供能不足的情况下,AMPK活性增强,此时,往往伴随着动用体脂分解供能,因此AM PK活性增强会促进脂肪酸分解,并通过抑制SREBP-1c的转录来抑制脂肪酸合成。

至于SREBP-1a和SREBP-2的转录,常在固醇缺乏的情况下被激活,SREBP-1a的转录激活通常在体外培养的细胞中实现[11]。而SREBP-2的转录主要是通过一个前馈机制,在SREBP-2基因中有固醇调节元件（stero l regulation elem ent,SRE）,细胞核中的SREBP-2（nSREBP-2）结合于SRE上,能激活SREBP-2自身的转录[37],有资料显示SREBP-1c也有类似的前馈调节[38-39]。

2.2 SREBPs在转录后水平的调节

SREBPs转录后水平的调节,概括起来可以分为3个途径:固醇介导的SCAP/SREBPs复合物从内质网到高尔基体的转运和加工活化过程,活化后的SREBPs的修饰过程以及泛素-26S蛋白酶体对活性nSREBPs的降解作用。

SREBPs翻译后的加工活化过程主要受细胞内固醇水平的调节。SREBPs基因转录成m RNA后,继而被翻译成蛋白质,该蛋白质无生物活性,被称为SREBPs的前体蛋白。SREBPs前体蛋白与SCAP紧密结合并锚定在内质网膜上。当细胞内固醇含量较充足时,SCAP与内质网上的insig蛋白（insulinsensitive protein,一种胰岛素敏感蛋白）结合,使得SREBPs前体蛋白停留在内质网膜上,不参加后续的加工过程;当细胞内固醇含量低于生理要求时, SCAP与insig蛋白断裂,此时SCAP起到一个运输和伴侣蛋白的作用,以小泡的形式运载着SREBPs前体蛋白到达高尔基体,在高尔基体的加工过程主要是由水解酶S1P（site 1 protease）和S2P（site 2 p rotease）起作用,经2步水解反应,释放出N端的转录激活区[40]。加工后的蛋白质是一个二聚体,称之为成熟的SREBPs,经细胞内核质转运受体（importinβ,负责细胞内大部分蛋白质和核酸分子的跨核膜转运）运输进入细胞核[41]内发挥作用。

成熟的SREBPs进入细胞核后,还要经过一系列的修饰才能发挥作用。在细胞核内,成熟的SREBPs转录激活作用一般通过共价键修饰或者通过与其他蛋白质的相互作用来调节[13]。进一步研究发现,胰岛素也能调节细胞核内成熟的SREBP-2和SREBP-1a的转录激活作用,这一调节主要通过活化的促细胞分裂蛋白激酶（m itogen-activated protein kinase,MAPK）途径来实现。Ser-117是成熟的SREBP-1a的MAPK途径的磷酸化位点[42]。体内和体外的试验结果证明:成熟SREBP-2的磷酸化位点是Ser-432和Ser-455[43]。但是,成熟SREBPs通过MAPK途径的磷酸化来调节转录激活的说法是有争议的,Ser-117也存在于SREBP-1c中,试验却证明了,SREBP-1c并没有通过MAPK的磷酸化途径来调节转录激活[44-45]。

具有转录催化活性的SREBPs在细胞核内还要受到泛素-26S蛋白酶体的快速降解。Botolin等[46]用试验证明加入26S的蛋白酶抑制剂后, SREBPs相对于未添加抑制剂组更加稳定,目的基因的表达也相应提高。

3 SREBPs对乳脂合成的调节

乳脂的成分很复杂,包括甘油三酯、甘油二酯、甘油一酯、甘油、游离脂肪酸和胆固醇等。其中甘油二酯、甘油一酯、甘油、长链脂肪酸是极低密度脂蛋白（V LDL）在乳腺毛细血管中在脂蛋白酯酶（LPL）的作用下分解生成,后被乳腺上皮细胞吸收,在乳腺上皮细胞内重新合成甘油三酯;中短链脂肪酸和少量胆固醇是乳腺上皮细胞内源合成的。Peterson等[47]用试验证明了,SREBPs也广泛分布于牛的乳腺组织中,即在乳腺组织中,SREBPs可以调节乳脂的生成。SREBPs的不同亚型作用的靶基因不同,它通过对不同靶基因的转录调节作用来实现对乳脂的内源合成和外源摄取的调节:SREBP-1c优先活化脂肪酸合成的相关酶,如FAS、ACC等,进而影响乳腺组织内中短链脂肪酸的内源合成;而SREBP-2则优先活化胆固醇生物合成的相关基因,如羟甲基戊二酸单酰CoA合酶（hydroxymet hylglutaryl CoA synthase HMG CoA synthase）和羟甲基戊二酸单酰CoA还原酶（hydroxym et hylglutaryl CoA reductase,HMG CoA reductase）等酶的基因[48-49],这些基因参与乳脂中的胆固醇酯的合成;另外,SREBPs的目的基因还包括脂肪酸转运蛋白（FATP）基因,甘油酯合成相关酶基因,例如:甘油-1-磷酸脂酰基转移酶（AGPAT）基因,长链脂肪酸酰基辅酶A合成酶（ACSL）基因[50],这些基因分别与乳腺长链脂肪酸的外源吸收和乳中甘油酯的合成有关。综上所述,SREBPs对乳脂含量和成分的调节有3个途径:1）可以通过影响甘油酯合成原料（中短链脂肪酸和胆固醇）的合成来间接影响乳脂的合成;2）可以通过调节脂肪酸转运蛋白来调节乳腺对脂类物质的吸收,进而影响乳脂含量;3）直接调节甘油酯合成相关酶来调节乳脂的合成。

4 小 结

SREBPs与脂肪酸合成有着密切的关系, SREBPs在奶牛的乳腺组织中广泛分布,对奶牛乳脂的调控有着重要意义。从分子水平探索SREBPs调控乳脂的机理,可为生产中常见的奶牛乳脂合成降低提供理论依据,进而起到指导生产的作用。

[1] SH IMANO H.Stero l regulatory element-binding p roteins（SREBPs）:transcrip tional regulators of lipid regulators of lipid synthetic genes[J].Progress in Lipid Research,2001,40（6）:439-452.

[2] MCPHERSON R,GAUTHIER A.Molecular regulation of SREBP function:the Insig-SCAP connection and iso form-specific modu lation of lipid synthesis[J].Biochem istry and Cell Biology,2004,82 （1）:201-211.

[3] HORTON JD,GOLDSTEIN J L,BROWN M S. SREBPs:activators o f the comp lete p rogram of cho lesterol and fatty acid synthesis in the liver[J]. The Journal of Clinical Investigation,2002,109: 1125-1131.

[4] DELPH INE E,BRONWYN H,PASCALE B,et al.SREBP transcrip tion factors:master regulators o f lipid homeostasis[J].Biochim ie,2004,86: 839-848.

[5] HUA X,SAKA IJ,HO Y K,et al.Hairpin orientation o f sterol regulatory elemen t-binding p rotein-2 in cellmembranes as determ ined by protease protection[J].The Journal of Bio logical Chem istry, 1995,270:29422-29427.

[6] BROWN M S,GOLDSTEIN J L.The SREBP pathw ay:regulation o f cholestero l metabo lism by proteolysis o f amembrane-bound transcription factor[J].Cell,1997,89（3）:331-340.

[7] HORTON JD,SH IMOM URA I.Sterol regulatory elem ent-binding proteins:activators of cholestero l and fatty acid biosynthesis[J].Current Opinion in Lipidology,1999,10（2）:143-150.

[8] TONTONOZ P,K IM J B,GRAVES R A,et al. ADD 1:a novel helix-loop-helix transcrip tion factor associated with adipocy te determ ination and differentiation[J].Molecular and Cellular Biology,1993,13:4753-4759.

[9] HUA X,YOKOYAMA C,WU J,et al.SREBP-2,a second basic-helix-loop-helix-leuc ine zipper protein t hat stim ulates t ranscrip tion by binding to a sterol regulatory element[J].Proceedings of the National A cademy Sciences o f United States o f A-merica,1993,90（24）:11603-11607.

[10] SH IMANO H,HORTON J D,SH IMOMURA I, et al.Iso form 1c o f sterol regu latory element binding protein is less active than isoform 1a in livers of transgenic m ice and in cultured cells[J].The Journal o f Clinical Investigation,1997,99:846-854.

[11] SH IMOMURA I,SH IMANO H,HORTON J D, et al.D ifferential expression o f exons 1a and 1c in mRNAs for sterol regulatory element binding protein-1 in hum an andm ouse organs and cu ltured cells [J].The Journal o f Clinical Investigation,1997, 99:838-845.

[12] HORTON JD,BASHMAKOV Y,SH IMOMURA I,et al.Regulation of sterol regulatory element binding proteins in livers o f fasted and refed m ice [J].Proceedings of the National Academ y Sciences of United States of America,1998,95:5987-5992.

[13] KIM JB,SARRAF P,WRIGHT M,et al.Nutritional and insulin regu lation o f fatty acid synthetase and lep tin gene expression through ADD 1/SREBP-1[J].The Journal of C linical Investigation,1998, 101:1-9.

[14] BIZEAU M E,MACLEAN PS,JOHNSON G C, et al.Skeletal muscle stero l regulatory element binding p rotein-1c decreases with food dep rivation and increasesw ith feeding in rats[J].The Journal of Nutrition,2003,133:1787-1792.

[15] COMMERFORD S R,PENG L,DUBE J J,et al.In vivoregu lation of SREBP-1c in ske letalmuscle: effects of nutritional status,glucose,insulin,and lep tin[J].American Journal of Physiology Regulatory,Integrative and Comparative Physiology, 2004,287:R218-R227.

[16] FORETZ M,PACOT C,DUGA IL I,et al. ADD1/SREBP-1c is required in the ac tivation of hepatic lipogenic gene expression by glucose[J]. Mo lecular and Cellu lar Biology,1999,19:3760-3768.

[17] DUCLUZEAU P H,PERRETTI N,LAVILLE M,et al.Regulation by insulin of gene expression in human ske letalm uscle and adipose tissue.Evidence for specific de fects in type2 diabetes[J].D iabetes,2001,50:1134-1142.

[18] SEWTER C,BERGER D,CONSID INE R V,et al.H uman obesity and type2 diabetes are associated w ith alterations in SREBP1 isoform expression that are rep roducedex vivoby tumor necrosis factor-alpha[J].D iabetes,2002,51:1035-1041.

[19] SH IMOM URA I,BASHMAKOV Y,IKEM OTO S,et al.Insulin selectively increases SREBP-1c m RNA in the livers of rats with strep tozotocin-induced diabetes[J].Proceedings of the National A-cademy Sciences of United States o f Am erica, 1999,96:13656-13661.

[20] AZZO UT-M ARNICHE D,BECARD D,GUICHARD C,et al.Insulin ef fects on sterol regulatory-elem ent-binding p rotein-1c（SREBP-1c）transcrip tional activity in rathepatocy tes[J].The Biochem ical Journal,2000,350（Pt.2）:389-393.

[21] FLEISCHMANN M,IYNEDJIAN P B.Regulation o f stero l regu latorye lement binding p rotein 1 gene expression in liver:ro le of insulin and p rotein kinase B/cAkt[J].The Biochem ical Journal,2000, 349:13-17.

[22] RIBAUX P G,IYNEDIJIAN P B.Analysis of the role o f p rotein kinase B（cAKT）in insulin-dependent induction o f glucokinase and stero l regulatory element-binding protein 1（SREBP1）mRNAs in hepatocy tes[J].The Biochem ical Journal,2003, 376:697-705.

[23] MATSUMOTO M,OGAWA W,AK IMOTO K,et al.PKC lam bda in liver mediates insulin-induced SREBP-1c expression and determ ines both hepatic lipid content and overall insu lin sensitivity[J].The Journal of Clinical Investigation,2003,112:935-944.

[24] PORSTM ANN T,GRIFFITHS B,CHUNG Y L, et al.PKB/Ak t induces transcription of enzymes involved in cholesterol and fatty acid biosynthesis via activation o f SREBP[J].Oncegene,2005,24 （43）:6465-6481.

[25] PEET D J,TURLEY SD,MA W,et al.Cholesterol and bile acidmetabolism are impaired inm ice lacking the nuclear oxystero l recep tor LXR alpha [J].Cell,1998,93:693-704.

[26] REPA J J,LIANG G,OU J,et al.Regulation of mouse sterol regulatory element-binding protein-1c gene（SREBP-1c）by oxysterol recep tors,LXR alpha and LXR beta[J].Genes and Developm ent, 2000,14:2819-2830.

[27] SCHULTZ J R,TU H,LUK A,et al.Role of LXRs in control of lipogenesis[J].Genes and Development,2000,14:2831-2838.

[28] LAFFITTE B A,CHAO L C,LI J,et al.Activation o f liver X recep tor imp roves glucose tolerance through coordinate regulation o f g lucose metabolism in liver and adipose tissue[J].Proceedings of the National A cadem y Sciences o f United States of America,2003,100:5419-5424.

[29] REPA J J,LIANG G,OU J,et al.Regulation of mouse stero l regulatory elementbinding p rotein-1c gene（SREBP-1c）by oxysterol receptors,LXR alpha and LXR beta[J].Genes Developmen t,2000, 14:2819-2830.

[30] JOSEPH SB,LAFFITTE B A,PATEL PH,et al. Direct and indirect mechanisms for regulation of fatty acid synthase gene expression by liver X recep tors[J].The Journal o f Biological Chem istry, 2002,277:11019-11025.

[31] ZHANG Y,YIN L,HILLGARTNERF B.SREBP-1 integrates the ac tions of thyroid hormone,insu lin, cAMP,and medium-chain fatty acids on ACC alpha transcrip tion in hepatocy tes[J].Journal of Lipid Research,2003,44:356-368.

[32] LIANG G,YANG J,HORTON JD,et al.D im inished hepatic response to fasting/refeeding and liver X receptor agonists in m ice with selective deficiency o f sterol regu latory element-binding p rotein-1c[J].The Journal o f Bio logical Chem istry,2002, 277:9520-9528.

[33] HEEMERS H,MAES B,FOUFELLE F,et al. Androgens stimulate lipogenic gene expression in prostate cancer cells by ac tivation of the sterol regu latory element-binding p rotein cleavage activating p rotein/sterol regulatory element-binding p rotein pathw ay[J].Molecular Endocrinology,2001,15: 1817-1828.

[34] HEEM ERS H,VANDERHOYDONC F,ROSKAMS T,etal.Androgens stimulate coordinated lipogenic gene exp ression in norm al target tissuesin vivo[J].M olecular and Cellular Endocrinology, 2003,205:21-31.

[35] LACASA D,LE LIEPVRE X,FERRE P,et al. Progesterone stim ulates adipocyte determ ination and dif ferentiation 1/sterol regulatory e lem entbinding protein 1c gene exp ression.Potential mechanism for the lipogenic effect o f progesterone in adipose tissue[J].The Journal o f Bio logical Chem istry,2001,276:11512-11516.

[36] MCFADDEN JW,CORL B A.Activation of AMP-activated p rotein kinase（AMPK）inhibits fatty acid synthesis in bovine mamm ary epithelial cells[J]. Biochem istry and Biophysical Research Communication,2009,390（3）:388-393.

[37] SATO R,INOUE J,KAWABE Y,et al.Steroldependen t transcrip tional regulation of stero l regulatory element-binding p rotein-2[J].The Journal o f Bio logical Chem istry,1996,271:26461-26464. [38] AMEM IYA-KUDO M,SHIMANO H,YOSHIKAWA T,et al.Promoter analysis of themouse sterol regu latory elementbinding p rotein-1c gene[J].The Journal o f Biological Chem istry,2000,275: 31078-31085.

[39] HORTON JD,GOLDSTEIN J L,BROWN M S. SREBPs:activators o f the comp lete p rogram of cho lesterol and fatty acid synthesis in the liver[J]. The Journal of Clinical Investigation,2002,109: 1125-1131.

[40] RAWSON R B.The SREBP pathw ay-insights from Insigs and insec ts[J].Nature Reviews M olecular Cell Biolog,2003,4（8）:631-640.

[41] LEE S J,SEK IMOTO T,YAMASH ITA E,et al. The struc ture of im portin-beta bound to SREBP-2: nuclear import of a transcription factor[J].Science,2003,302:1571-1575.

[42] ROTH G,KOTZKA J,KREMER L,et al.MAP kinases Erk1/2 phosphory late sterol regulatory element-binding p rotein（SREBP）-1a at serine 117in vitro[J].The Journal of Biological Chem istry, 2000,275:33302-33307.

[43] KOTZKA J,LEHRS,ROTH G,etal.Insulin-ac-tivated Erk-m itogen-activated protein kinases phosphory late sterol regulatory element-binding protein-2 at serine residues 432 and 455in vivo[J]. The Journal of Biological Chem istry,2004,279: 22404-22411.

[44] WANG D,SUL H S.Insulin stimulation o f the fatty acid synthase p rom oter is mediated by the phosphatidylinositol 3-kinase pathw ay.Involvement of protein kinase B/Ak t[J].The Journal of Biological Chem istry,1998,273:25420-25426.

[45] IYNEDJIAN P B,ROTH R A,FLEISCHMANN M,et al.Ac tivation o f p rotein kinase B/cAk t in hepatocytes is suf ficient for the induction of exp ression of the gene encoding glucokinase[J].The Biochem ical Journal,2000,351（Pt.3）:621-627. [46] BOTOLIN D,WANG Y,CHRISTIAN B,et al. Docosahexaneoic acid（22∶6,n-3）regu lates rat hepatocyte SREBP-1 nuclear abundance by Erkand 26S proteasome-dependent pathw ays[J].Journal o f Lipid Research,2006,47:181-190.

[47] PETERSON D G,MATITASHV ILI E A,BAUMAN D E.The inhibitory effect o ftrans-10,cis-12 CLA on lipid synthesis in bovinem ammary epithelial cells invo lves reduced proteolytic activation o f the transcrip tion factor SREBP-1[J].The Journal o f Nutrition,2004,134:2523-2527.

[48] PAI J,GURYEV O,BROWN M S,et al.Differential stimu lation o f cholestero l and unsaturated fatty acid biosynt hesis in cells exp ressing individual nuclear sterol regulatory element-binding proteins [J].The Journal o f Biological Chem istry,1998, 273（40）:26138-26148.

[49] HORTON JD,SH IMOMURAL I,BROWN M S, et al.Activation o f cholesterol synthesis in p reference to fatty acid synt hesis in liver and adipose tissue of t ransgenic m ice overproducing sterol regulatory element-binding p rotein-2[J].The Journal of Clinical Investigation,1998,101（11）:2331-2339. [50] BIONAZ M,LOOR JJ.ACSL1,AGPAT 6,FABP3, LPIN1,and SLC27A 6 are the most abundant isoforms in bovine mammary tissue and their expression is af fected by stage of lactation[J].The Journalof Nutrition,2008,138:1019-1024.

*Correspond ing au thor,p rofessor,E-m ail:w ryang@sdau.edu.cn

（编辑 武海龙）