动物营养学报 >

2023 , Vol. 35 >Issue 9: 5545 - 5554

DOI: https://doi.org/10.12418/CJAN2023.511

综述

维生素D调控动物脂肪形成及脂肪组织代谢的研究进展

  • 符璐 ,
  • 苗健 ,
  • 张国华 ,
  • 卢建雄 , *
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  • 西北民族大学生命科学与工程学院,兰州 730124
* 卢建雄,教授,博士生导师,E-mail:

符璐(1998—),女,辽宁锦州人,硕士研究生,动物营养与饲料科学专业。E-mail:

Copy editor: 陈鑫

收稿日期: 2023-03-24

  网络出版日期: 2023-09-13

基金资助

国家自然科学基金项目(31860633)

西北民族大学中央高校基本科研业务费项目

收起

Research Advances in Regulation of Animal Adipogenesis and Adipose Tissue Metabolism by Vitamin D

  • FU Lu ,
  • MIAO Jian ,
  • ZHANG Guohua ,
  • LU Jianxiong , *
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  • College of Life Science and Engineering, Northwest Minzu University, Lanzhou 730124, China
* professor, E-mail:

Received date: 2023-03-24

  Online published: 2023-09-13

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摘要

维生素D(VD)除调节钙稳态和骨代谢外,也广泛参与细胞增殖和分化、免疫及细胞代谢等生物学过程。脂肪组织贮存VD,并在所表达的VD代谢酶的催化下,将其转化为活性形式1,25-二羟基维生素D3[1,25(OH)2D3],以自分泌、旁分泌和/或内分泌方式,通过VD受体产生其生物学效应。本文综述了VD在脂肪组织的贮存、代谢及对脂肪形成、脂肪因子分泌、炎症反应的影响和机制,并介绍了饲粮添加VD影响猪生长性能、肉品质和健康的研究进展,以期为采取营养措施控制猪脂肪沉积和改善肉品质提供参考。

关键词： 维生素D; 代谢; 生物学效应; 脂肪形成; 猪

本文引用格式

符璐 , 苗健 , 张国华 , 卢建雄 . 维生素D调控动物脂肪形成及脂肪组织代谢的研究进展[J]. 动物营养学报, 2023 , 35(9) : 5545 -5554 . DOI: 10.12418/CJAN2023.511

Abstract

In addition to regulating calcium homeostasis and bone metabolism, vitamin D (VD) is also widely involved in multiple biological processes, such as cell proliferation and differentiation, immunity and cell metabolism. Adipose tissues store VD and express vitamin D metabolizing enzymes, and convert VD into its active form 1α,25-dihydroxyvitamin D3 [1,25(OH)2D3]. 1,25(OH)2D3 exerts biological effects through vitamin D receptor (VDR) in an autocrine, paracrine and /or endocrine manner. It is reviewed on progresses in the storage, metabolism and the effect of VD on adipogenesis, adipocytokines and inflammation in adipose tissues in this paper. Moreover, the advances on the effects of supplementary VD in diet on growth performance and health of pigs is introduced, to provide the clues for taking nutritional measures to control fat deposition and improve pork quality.

Key words： vitamin D; metabolism; biological effect; adipogenesis; pig

维生素D(vitamin D,VD)是一类固醇类衍生物,因其侧链结构不同而有多种形式。VD兼具维生素和激素的特性,在动物体发挥功能的主要为麦角钙化醇(维生素D2, VD2)和胆钙化醇(维生素D3, VD3)。动物体VD除通过食物摄取外,也经紫外线照射在皮肤将7-脱氢胆固醇转化为VD3。VD对钙磷吸收、利用、代谢稳态及骨骼、牙齿的发育和健康起着关键调节作用。然而,近年的研究表明,脂肪组织作为VD的主要贮存场所,也表达VD羟化酶,催化生成VD的活性形式1,25-二羟基维生素D3[1,25(OH)2D3],以自分泌、旁分泌或内分泌方式影响非经典靶组织的生物学功能[1]。通过VD受体(vitamin D receptor,VDR)的介导,VD以其活性形式调节脂肪组织多种生物学过程,包括脂肪细胞增殖、分化和脂肪合成及脂肪细胞因子表达、炎症反应等。本文综述了VD在脂肪组织和脂肪细胞的代谢、生物学效应及其作用机制,并介绍了饲粮中添加VD对猪生长性能、健康及肉品质影响的研究进展,为探讨利用营养途径调控猪脂肪沉积及改善胴体质量和肉品质提供参考。

1 脂肪组织及脂肪细胞VD代谢

1.1 VD及其代谢产物在脂肪组织的贮存、摄取和释放

脂肪组织贮存VD,VD及其代谢产物与脂滴结合,主要以胆钙化醇、25羟基维生素D3[25(OH)D3]和1,25(OH)2D3的形式存在[2]。机体65%以上的VD为VD3,其中73%的VD3贮存于脂肪组织。人内脏脂肪中VD含量比皮下脂肪高20%,女性肥胖者与体重正常者内脏脂肪和皮下脂肪VD的分布相似,但女性肥胖者脂肪组织VD含量更高[3]。脂肪组织胆钙化醇的积累存在明显的个体差异,且与血浆25(OH)D3含量无关,但脂肪组织中25(OH)D3的含量与血浆25(OH)D3含量呈正相关[4]。脂肪组织和脂肪细胞摄取VD的分子调控机制尚不清楚,但对25(OH)D3的摄取可能与低密度脂蛋白受体家族单程跨膜受体(Megalin)/内因子维生素B12受体(Cubilin)通路的介导有关[5]。Cubilin是小鼠脂肪组织和脂肪细胞摄取25(OH)D3的主要蛋白质,负责在Megalin蛋白内化之前隔离VD结合蛋白(vitamin D-binding protein,VDBP)-25(OH)D3复合物[6]。
脂肪组织可将VD缓慢释放到血液循环中,维持血液25(OH)D3的相对稳定。脂解作用参与VD的释放,在脂肪组织脂肪沉积过度后,具有脂解反应迟缓、血液VD水平低的特征。研究表明,肥胖患者脂肪组织功能的失调导致儿茶酚胺诱导的VD和25(OH)D3释放减少[7],β肾上腺素介导的腹部皮下脂肪组织脂解钝化,减缓1,25(OH)2D3的释放[8]。

1.2 VD在脂肪组织和脂肪细胞的代谢

无论外源性还是内源性VD均通过血液循环进入肝脏,经25-羟化酶催化合成25(OH)D3。25(OH)D3是VD的主要循环形式,其血清含量通常被作为VD营养状态的标志。多种微粒体细胞色素P450酶(microsomal cytochrome P450,CYP450)催化钙化醇25-羟基化,如CYP2C11、CYP3A4和CYP2J2,其中CYP27A1和CYP2R1是25-羟基化的关键酶[9]。人类脂肪组织检测到CYP27A1、CYP2R1和CYP2J2表达,表明脂肪组织及脂肪细胞可将VD羟基化为25(OH)D3[10]。Zoico等[11]也证明,3T3-L1脂肪细胞表达CYP27A1,从而发生25-羟基化生成25(OH)D3,且VD处理可上调CYP27A1表达。然而,CYP2R1基因敲除小鼠血清25(OH)D3含量仅比野生型降低50%,说明其他酶也参与维持血液25(OH)D3含量或补偿CYP2R1的功能障碍[12]。
25(OH)D3与VD结合蛋白(VDBP)结合,通过血液循环转运到肾脏及其他组织器官,经1α-羟基酶的作用转化为1,25(OH)2D3,活性大幅度提高,然后转运到靶器官与靶器官的核受体VDRn或膜受体VDRm结合,发挥其相应生物学效应[6]。在人类脂肪组织、前体脂肪细胞及新分化的脂肪细胞表达催化25(OH)D3转化为1,25(OH)2D3的1α-羟基化的关键酶CYP27B1[13]。同样,3T3-L1脂肪细胞表达CYP27B1,胆钙化醇可诱导其表达[11]。猪脂肪源间充质干细胞表达CYP27B1,其活性被抑制后,1,25(OH)2D3含量显著降低[14]。这些证据表明,脂肪组织及其脂肪细胞发生VD的1α-羟基化,能将非活性VD转化为其活性形式。
24-羟化酶CYP24A1催化25(OH)D3和1,25(OH)2D3分解为骨化酸和其他非活性代谢产物,1,25(OH)2D3可诱导CYP24A1表达,促进自身降解[15]。人类皮下脂肪组织和内脏脂肪组织表达CYP24A1,在人和小鼠脂肪细胞及猪脂肪源间充质干细胞也发现CYP24A1表达[14]。由此可见,VD的活性形式在脂肪组织和脂肪细胞可被降解,最终通过失活途径进行自我调节,从而保持相对稳定。

1.3 脂肪组织和脂肪细胞VD代谢的调节

已发现有多种因素通过影响VD代谢酶及其编码基因表达影响VD代谢。小鼠短期补充胆钙化醇,可通过下调皮下脂肪组织CYP27A1、CYP24A1和Cublin mRNA表达,减少脂肪细胞对25(OH)D3的摄取和25-羟基化,防止25(OH)D3在脂肪组织过度积累[6]。1,25(OH)2D3促进猪脂肪源间充质干细胞CYP24A1和CYP27B1表达,抑制CYP酶活性,显著降低活性VD水平,即1,25(OH)2D3可抑制活性VD合成,同时也促进其失活[14]。α-亚麻酸和亚油酸丰富的饲粮均降低肥育猪皮下脂肪组织和背最长肌VD含量,影响CYP2J2、CYP27A1、CYP2R1和CYP27B1表达水平,并存在组织部位的差异[16],然而尚不清楚是否通过影响VD代谢调控脂肪生成。
肥胖也对脂肪组织VD代谢产生影响。高脂饲粮诱导的肥胖小鼠,脂肪组织25(OH)D3积累增加,CYP2R1 mRNA表达水平提高,说明肥胖不仅有利于VD的摄取和贮存,也促进25-羟基化[17]。然而,肥胖人群皮下脂肪组织CYP2J2和CYP27B1表达降低,胖瘦人之间CYP24A1表达没有差异[10,18],但肥胖者体重减轻后其表达水平提高[10]。

2 VD对脂肪细胞和脂肪组织的生物学效应

脂肪细胞来源于间充质干细胞(mesenchymal stem cells,MSCs)。MSCs首先发育为前体脂肪细胞,然后终末分化为成熟脂肪细胞。前体脂肪细胞经历形态学和生物化学改变,转变为功能性脂肪细胞,执行脂质合成、脂肪酸跨膜运输、胰岛素信号应答和脂肪因子分泌等多种功能。因此,脂肪形成是前体脂肪细胞增殖、分化及脂肪合成等系列生物过程的结果。

2.1 VD调控细胞成脂分化

VD对脂肪形成的影响已有许多研究,然而,对不同细胞源的研究得出不同结果。对3T3-L1前体脂肪细胞的研究表明,1,25(OH)2D3显著抑制细胞成脂分化,减少脂质积累[19]。1,25(OH)2D3通过下调增强子结合蛋白α(CCAAT/enhancer binding protein α,C/EBPα)、C/EBPβ、过氧化物酶体增殖物激活受体γ (peroxisome proliferators-activated receptors γ,PPARγ)及脂肪酸结合蛋白(fatty acid-binding protein,FABP)等成脂分化重要调节因子的表达,阻断成脂分化程序,抑制脂肪形成[20-21]。1,25(OH)2D3及过表达VDR均可抑制小鼠棕色脂肪细胞成脂分化及PPARγ的反式激活活性[22]。1,25(OH)2D3通过增强自噬和调节磷脂酰肌醇3-激酶(PI3K)/蛋白激酶B(Akt)/哺乳动物雷帕霉素靶蛋白(mTOR)/细胞肿瘤抗原p53(p53)信号通路,抑制白色脂肪细胞棕色化及其标志基因表达[19]。然而,尽管1,25(OH)2D3以剂量依赖和时间依赖方式作用于多个靶点抑制3T3-L1细胞分化,但只影响成脂分化的早期事件。
细胞成脂分化是C/EBPα、C/EBPβ和PPARγ等多种转录调控因子协同作用的复杂生物学过程,其中PPARγ是其他因子不可替代的关键转录因子[23]。VD对成脂分化的抑制作用可能涉及多个调控通路。1,25(OH)2D3通过下调PPARγ和C/EBPβ表达,并诱导C/EBPβ的辅阻遏物ETO蛋白,进一步降低C/EBPβ活性,抑制3T3-L1前体脂肪细胞分化[24]。Wnt/β-连环蛋白(β-catenin)通路在成脂分化期间通常被下调,Cianferotti等[25]对骨髓基质干细胞的研究发现,1,25(OH)2D3下调dickkopf相关蛋白1(dickkopf-related protein 1,DKK1)和分泌型卷曲相关蛋白2(secreted frizzled-related protein 2,SFRP2)等Wnt信号通路的抑制因子表达,抑制成脂分化及脂肪细胞标志基因FABP和Adipsin表达。细胞外信号调节激酶(extracellular signal-regulated kinase,ERK)是丝裂原活化蛋白激酶(mitogen activated protein kinase,MAPK)信号之一,1,25(OH)2D3通过抑制ERK表达和磷酸化,下调C/EBPα、PPARγ、C/EBPβ及维持WNT/β-catenin信号通路,抑制3T3-L1细胞分化[20]。此外,1,25(OH)2D3对PPARγ活性的拮抗及VDR蛋白稳定性的影响,也是成脂分化调控过程的重要环节[21]。
与上述对3T3-L1脂肪细胞系等的抗成脂作用相反,1,25(OH)2D3促进人和小鼠原代前体脂肪细胞分化,上调FABP4、脂联素和PPARγ表达[13]。25(OH)D3通过诱导11-β-羟基类固醇脱氢酶1(11β-hydroxysteroid dehydrogenase 1,HSD11β1)及PPARγ、C/EBP等成脂分化基因表达,促进小鼠脂肪MSCs成脂分化,增强胰岛素诱导的葡萄糖摄取[26]。25(OH)D3和1,25(OH)2D3促进人皮下前体脂肪细胞分化及FABP4和脂蛋白脂肪酶(lipoproteinlipase,LPL)表达[13],促进人脂肪源MSCs成脂分化及脂肪酸合酶(fatty acid synthase,FAS)、FABP4和PPARγ表达[27]。
VD对细胞成脂分化研究结果的差异分歧显然与细胞的来源及其生物学特性有关,但也可能与其时间依赖性和剂量依赖性有关。在3T3-L1脂肪细胞分化早期,转录因子C/EBPβ对启动分化程序发挥重要作用,并反式激活成脂关键因子C/EBPα和PPARγ转录表达[28]。1,25(OH)2D3以剂量依赖方式抑制3T3-L1细胞分化及C/EBPα和PPARγ转录表达,但对分化启始后24~48 h的细胞分化和C/EBPβ表达无显著影响,表明VD仅抑制3T3-L1细胞成脂分化程序的早期事件[21]。在分化后期,1,25(OH)2D3提高C/EBPα和PPARγ表达,但对C/EBPβ表达没有显著影响。此外,作为VD发挥效应的核受体VDR,在脂肪细胞分化早期表达,随着分化的进程其表达水平显著降低[13]。然而,VD影响细胞成脂分化的时间依赖性是否取决于C/EBPβ和/或VDR及二者间的相互关系尚不明确。
此外,高剂量(10 nmol/L)1,25(OH)2D3促进人脂源性间充质干细胞成脂分化及PPARγ、C/EBPα表达,而低剂量(0.1 nmol/L)抑制其成脂分化,下调C/EBPα表达,但对PPARγ表达没有显著影响[29]。0.1~1 nmol/L浓度的1,25(OH)2D3抑制猪前体脂肪细胞分化,降低PPARγ和FAS表达,但浓度为10~100 nmol/L时,促进猪前体脂肪细胞分化,上调PPARγ和FAS表达[30]。然而,VD对动物体内脂肪形成的影响是否存在这种剂量依赖性尚不清楚。
VD也通过多种途径调节脂肪代谢,影响脂肪酸组成。1,25(OH)2D3通过上调沉默信息调节因子1(silent information regulator 1,Sirt1)表达和AMPK磷酸化等非胰岛素依赖性信号通路,上调葡萄糖转运子4(glucose transporter 4,Glut4)表达及易位到细胞表面,促进胰岛素受体底物1 (IRS1)/PI3K/磷脂酰肌醇三磷酸(PIP3)/Akt/蛋白激酶Cζ(PKCζ)信号级联,增强葡萄糖摄取[31]。然而,1,25(OH)2D3可通过下调丙酮酸羧化酶,降低葡萄糖作为底物从头脂肪酸合成的利用率,上调脂肪酸β-氧化和脂解酶相关基因表达,减少3T3-L1脂肪细胞脂质积累[32]。VD通过降低从头脂肪合成关键酶基因的表达,减少肝脏和皮下脂肪组织甘油三酯积累[33]。此外,Ji等[34]关于VDR敲除小鼠的研究证明,VD配体结合的VDR与长链脂肪酸延伸酶3(fatty acid elongase 3,Elovl3)基因启动子近端区域的负反应元件结合,抑制Elovl3基因表达,以组织特异性方式调控脂肪组织脂肪酸组成,影响C18-C24饱和与单不饱和脂肪酸含量。

2.2 母体VD缺乏影响子代脂肪组织生物学编程

妊娠期摄入充足的VD对胎儿发育至关重要,母体VD缺乏将引起后代未来的代谢紊乱,产生一系列不良后果[35]。近来的研究表明,母体VD缺乏影响子代脂肪组织代谢的编程。VD缺乏母鼠所产雄性幼鼠体重较低,由于脂肪组织转录谱改变,成年后易于肥胖和葡萄糖稳态受损,但对同窝雌鼠没有显著影响[36]。与此一致,大鼠妊娠前和妊娠期缺乏VD,可促进其雄性后代前体脂肪细胞增殖与分化,形成肥胖表型[37]。小鼠母体VD缺乏可造成雄性后代子宫内生长迟缓,易于形成肥胖和葡萄糖不耐受等肥胖表型[38]。这种现象可能与表观遗传变化包括后代基因启动子和CpG岛的甲基化差异[37]及肝脏和生殖细胞DNA甲基化中断有关[39]。此外,母鼠VD缺乏以性别依赖方式激活后代脂肪组织炎症反应通路,并可能与核因子-κB(nuclear factor-kappa B,NF-κB)信号通路的激活相关[40]。

2.3 VD调控脂肪组织脂肪因子分泌

脂肪细胞分泌瘦素、脂联素和抵抗素等多种脂肪因子,以内分泌、旁分泌或自分泌等方式,调控机体代谢及能量平衡。研究表明,VD调节许多脂肪因子的分泌[24]。脂联素是一种由分化的脂肪细胞特异性产生的血清蛋白,具有抗炎和胰岛素增敏作用。与其他脂肪因子不同,血液脂联素浓度与体质指数呈负相关。肥胖儿童由于VD缺乏,导致脂联素水平降低[41],2型糖尿病患者补充VD,可显著提高血清脂联素水平[42]。
瘦素由脂肪细胞分泌,其血清水平与体脂含量呈正相关。瘦素作用于中枢神经系统的受体,抑制食欲,增加能量消耗,并通过抑制脂肪生成和促进脂解控制脂质代谢[43]。CYP27B1基因敲除小鼠由于缺乏1α-羟化酶,瘦素水平降低,饲粮消耗明显增加,而VDR敲除小鼠由于血清瘦素含量降低,采食量升高但机体消瘦[44]。1,25(OH)2D3提高野生型小鼠脂肪组织瘦素基因mRNA表达和血清瘦素水平,促进其脂肪组织培养物瘦素表达和分泌,但对VDR缺失小鼠无显著影响[45]。Kaneko等[46]报道,1,25(OH)2D3抑制小鼠脂肪细胞瘦素表达至少84%,但诱导人胶质母细胞瘤细胞瘦素表达15.1倍,说明VD可能通过调控瘦素表达调节食物摄入。由此可见,VD通过调节瘦素水平影响机体能量稳态和脂质代谢,但可能具有组织细胞特异性。

2.4 VD调节脂肪组织炎症反应

脂肪组织含有丰富的与脂肪细胞相互作用的调节性T细胞和B细胞、自然杀伤 (natural killer,NK)细胞、树突状细胞及巨噬细胞等免疫细胞,其中脂质相关巨噬细胞(lipid-associated macrophages,LAM)以Trem2信号依赖方式调节脂质代谢、脂肪细胞肥大和炎症反应[47]。研究表明,VD降低脂多糖诱导的急性炎症小鼠和食物诱导的代谢性炎症小鼠脂肪细胞促炎细胞因子和趋化因子水平[48]。人血清促炎细胞因子白细胞介素(interleukin,IL)6和肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)含量与25(OH)D3含量呈负相关,而超重和肥胖患者血浆脂联素水平与25(OH)D3含量存在负相关[49]。缺乏VD的2型糖尿病人补充VD可降低血清IL-6、纤溶酶原激活物抑制物-1和纤维蛋白原水平,减轻氧化应激和炎症[42]。补充VD的小鼠虽然不能改善高脂高糖饲喂诱导的肥胖及脂肪细胞肥大和葡萄糖稳态,但可通过AMPK/NF-κB信号通路降低脂肪组织IL-6、TNF-α等促炎因子及趋化因子表达,有助于减轻脂肪组织炎症[33,50]。
体外研究也表明,VD减少脂肪细胞趋化因子和细胞因子释放。1,25(OH)2D3通过抑制NF-κB和MAPK信号通路,对脂肪细胞产生抗炎作用[51]。Toll样受体(Toll-like receptors,TLR)是一种跨膜蛋白,通过启动信号级联,导致NF-κB等转录因子激活,调控细胞因子表达。VD可通过降低TLR表达抑制NF-κB信号通路,减少促炎细胞因子表达和分泌[48]。

3 VD作用的分子调控机制

VD的基因组效应依赖于1,25(OH)2D3对核受体VDR的激活,并涉及表观基因组的变化,导致转录组和蛋白质组改变[52]。VDR广泛表达于各类组织细胞[53],1,25(OH)2D3通过VDR以组织和细胞特异性方式直接或间接调控上千个靶基因表达[52],包括NF-κB、C/EBP及信号转导和转录激活因子5(signal transducer and activator of transcription 5,STAT5)[54]。前体脂肪细胞及脂肪细胞分化早期表达VDR,用siRNA敲除3T3-L1细胞VDR,脂肪形成被抑制[20]。用1,25(OH)2D3处理可阻滞VDR+/+细胞成脂分化,但对VDR-/-细胞无显著影响[21]。可见,VD通过与其配体VDR结合,调控下游靶基因表达及脂肪形成。
研究表明,VDR与维甲酸X受体(retinoid X receptor,RXR)形成异二聚体后易位到细胞核,在靶基因启动子区的VD反应元件(vitamin D response elements,VDRE)与DNA结合。在缺乏1,25(OH)2D3时,无配体结合的VDR异二聚体可以结合基因组DNA,但随后与共阻遏蛋白和组蛋白去乙酰化酶形成复合物[53]。相反,当存在1,25(OH)2D3时,配体激活的VDR征募辅激活因子和组蛋白乙酰转移酶,导致转录激活[1]。肥胖者脂肪组织VDR表达较体重正常者显著提高[18],也支持了脂肪细胞VD活性形式代谢物的基因组效应。
VD及其活性代谢物也通过表观遗传效应发挥其调控功能[37],这些效应包括通过调节DNA甲基转移酶和/或去甲基化酶的表达,影响DNA甲基化[55]。VD缺乏导致DNA甲基化程度降低,诱导脂肪组织组蛋白去乙酰化酶及IL-12A、NF-κB等脂肪因子表达[56]。VD也可通过激活组蛋白乙酰转移酶和组蛋白去乙酰化酶调控组蛋白乙酰化,以及组蛋白甲基化和去甲基化,调控转录因子的染色质可及性[57]。此外,VD参与调节miRNA表达,人类脂肪组织VDR的表达可能受miR-125a-5p、miR-125b-5p和miR-214-3p等miRNA的调控,并影响促炎细胞因子IL-6、IL-8和IL-1 mRNA表达[18]。然而,VD及其代谢物对其他表观遗传机制的影响仍有待研究。
与需要若干小时经历RNA和蛋白质合成才能实现的基因组效应相比,VD激活信号通路的快速反应只需几秒至几分钟,排除了通过激活VDR转录表达参与的过程,即VD的作用存在无需VDR参与的非基因组效应[58]。研究证实,活性形式的VD促进磷脂酶A2、磷脂酰肌醇-3激酶与钙转运蛋白等质膜蛋白相互作用,促使第二信使如钙离子(Ca2+)、环磷酸腺苷和磷脂酰肌醇3,4,5三磷酸产生,最终激活蛋白激酶C、MAPK和Ca2+-钙调蛋白激酶Ⅱγ,以及介导Ca2+和氯离子(Cl-)通道开放,影响多种生物学过程[59]。这些通过膜受体快速启动的非基因组效应依赖于蛋白质二硫键异构酶家族A成员3(protein disulfide-isomerase 3,PDIA3)[58,60]。PDIA3在脂肪细胞表达,可能是胰岛素抵抗和脂代谢异常相关内质网应激的早期标志物[61],但在脂肪细胞VD的非基因组效应中该蛋白质的作用尚不清楚。

4 VD影响猪生长性能、健康和肉品质

在饲养标准规定的营养需要量的基础上,添加VD有助于改善猪的生长性能和健康。饲粮添加50 μg/kg的25(OH)D3,除改善断奶仔猪骨质量和钙消化率[62-63]、生长肥育猪骨矿物质含量和骨质强度[64]外,可改善仔猪和生长猪的生长性能[62-63]、抗氧化能力及肠道分泌型免疫球蛋白A(secretory immunoglobulin A,sIgA)分泌和微生物β多样性[62],提高生长肥育猪抗氧化能力、改善肉品质和肠道微生物组成[64]。母猪饲粮添加50 μg/kg的25(OH)D3可提高哺乳仔猪断奶前生长速度[65-66]、改善母猪及其仔猪营养状况,并增加初生仔猪初级肌纤维数量[67]。妊娠期母猪补充50 μg/kg VD3可改善哺乳仔猪肠道功能和菌群结构[68]。饲粮添加高剂量25(OH)D3可提高断奶仔猪血清25(OH)D3含量,增加辅助性T细胞和细胞毒性T细胞,改善免疫和抗氧化性能[69]。
猪是脂肪沉积能力最强的动物之一,控制皮下脂肪沉积及适当提高肌内脂肪含量对于提高养猪生产效益和改善猪肉品质意义重大。不同浓度1,25(OH)2D3可改变活性氧(ROS)含量和还原型谷胱甘肽(GSH)/氧化型谷胱甘肽(GSSG)比值,调节细胞氧化还原状态,影响体外培养猪前体脂肪细胞分化[70]。饲粮添加适量25(OH)D3(50 μg/kg),猪背最长肌饱和及单不饱和脂肪酸含量显著降低[63]。然而,VD对猪脂肪组织发育及脂肪沉积的作用仍知之甚少。

5 小结与展望

脂肪细胞分化是动物脂肪沉积的细胞学基础。脂肪的沉积和分布是营养物质与遗传因子相互作用的结果,皮下脂肪影响胴体质量,而肌内脂肪直接影响猪肉品质。利用营养物质调控脂肪形成及肉品质,是动物产品安全、健康生产的重要措施。在人和啮齿动物体内外的研究均已证明,VD对脂肪组织和脂肪细胞产生多种生物学效应,通过多种途径调节脂肪形成。然而,脂肪形成是多种调控因子共同作用的复杂生物学过程,各种成脂因子在脂肪细胞发育的不同阶段发挥着不同作用;动物遗传背景不同,脂肪细胞的发育从胎儿到出生后的各生长阶段存在时间差异。因此,亟待明确VD在动物体内脂肪形成中的作用及其发挥作用的时间效应。

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