动物营养学报    2020, Vol. 32 Issue (7): 2947-2958    PDF    
肌内脂肪沉积的营养调控与分子机制
王寒凝 , 祁智 , 李雪玲 , 相金柱     
内蒙古大学省部共建草原家畜生殖调控与繁育国家重点实验室, 呼和浩特 010070
摘要: 随着生活水平的提升,人们对肉品质的要求日益增高。肉品质主要受到肌内脂肪(IMF)含量、肌纤维类型及直径等影响。其中,IMF是指沉积在肌纤维与肌束之间的脂肪,其含量不同使肌肉中呈现不同程度的大理石花纹,直接影响色泽、风味、多汁性、嫩度等肉品质指标,与肉品质紧密相关。因此,提高IMF含量而不增加皮下脂肪含量有助于提升肉品质,满足人们对健康和口味的双重需求,提升经济价值。本文从IMF细胞来源、IMF含量与肉品质的关系、IMF沉积与营养调控、调控IMF沉积的分子机制等方面进行综述。
关键词: 肌内脂肪    肉品质    营养调控    分子机制    
Nutritional Regulation and Molecular Mechanism of Intramuscular Fat Deposition
WANG Hanning , QI Zhi , LI Xueling , XIANG Jinzhu     
The State Key Laboratory for Reproductive Regulation and Breeding of Grassland Livestock, Inner Mongolia University, Hohhot 010070, China
Abstract: As living standards improved, the requirement for meat quality in people's diet is growing. The meat quality is affected by intramuscular fat (IMF) contents, types and diameters of muscle fibers. IMF is the fat deposited between muscle fibers and muscle bundles. The IMF content variation, which is closely related to meat quality, leads to marbling in different degrees, directly affecting meat quality parameters including color, flavor, juiciness and tenderness. Therefore, increasing IMF content but not subcutaneous fat contributes to improving meat quality, satisfies the requirement of people to the health and tastes and raises economic values. This review discussed the IMF cell origin, relationship between IMF content and meat quality, IMF deposition and nutrition regulation, and molecular mechanism of IMF deposition.
Key words: IMF    meat quality    nutritional regulation    molecular mechanism    

随着人们生活水平的不断改善,消费者对肉品质的要求日益增高。肉品质受多种因素的影响,其中肌内脂肪(IMF)含量是重要的影响因素之一,如何通过调控IMF含量来改善肉品质是畜牧业面临的关键问题之一。已有较多研究报道了IMF含量与肉品质的关系及相关调控机制,本文将对此展开综述。

1 IMF细胞的来源

对于哺乳动物而言,脂肪组织主要沉积在皮下、腹腔、肌间、肌内。脂肪细胞数量在出生前和生长发育早期基本固定,脂肪沉积量由脂滴大小决定[1]。脂肪增殖主要包括2种形式:一是早期胚胎发育时期和出生期,受基因和母体营养调控实现脂肪细胞数量增加;二是胚胎发育后期及生长发育期,脂肪细胞体积增大[1-2]。不同部位的脂肪细胞按时间顺序形成并沉积为脂肪,肾周脂肪细胞在出生后基本停止增长,皮下和内脏脂肪细胞在出生后增长较少,生长期主要通过已有脂肪细胞增大实现脂肪沉积,IMF细胞形成较晚,大理石花纹主要在性成熟后开始明显沉积[3]。肌肉组织主要包括肌纤维、脂肪细胞、结缔组织等,肌肉和脂肪细胞的比例随IMF沉积量而变化。

哺乳动物体内脂肪组织主要存在3种脂肪细胞:白色、棕色、米色脂肪细胞[4]。白色和米色脂肪细胞由MYF5-/PAX7-干细胞分化而来,棕色脂肪细胞由MYF5+/PAX7+干细胞分化而来[5-6]。胚胎发育时期间充质细胞首先定型分化为肌肉细胞和脂肪-纤维细胞谱系,随后生肌祖细胞发育成肌纤维和卫星细胞,脂肪-纤维祖细胞发育成肌肉中的基质血管,而基质血管正是脂肪细胞、成纤维细胞及未分化的脂肪-纤维祖细胞存在之处[7-8]。关于IMF细胞来源及谱系追踪研究较少。研究表明,IMF细胞源于肌肉组织中PAX3-非卫星细胞(MYF5-/PAX3-细胞谱系)[9],也有报道称肌肉中分离的卫星细胞可增殖分化为脂肪细胞[10-11]。此外,诸多研究表明PDGFRa+非肌源性间充质细胞群是IMF细胞主要来源[12-14],PDGFRa+细胞群可分化为充满脂滴的脂肪细胞和纤维/脂肪生成祖细胞,PDGFRa+成纤维细胞定位在肌纤维和肌束之间,正是IMF沉积之处[12-13, 15]。因此,IMF细胞最有可能源自间充质细胞或肌肉卫星细胞,但干细胞或祖细胞群分化形成肌肉、脂肪、成纤维细胞的机制尚不清楚,目前IMF细胞的准确来源仍需进一步探索。

2 IMF含量与肉品质的关系

IMF可提升肉的色泽、嫩度、多汁性、系水力及风味,是评价肉品质的重要指标[16]。IMF含量低使得肉质干且味道差[17],人们可接受的IMF最低含量是牛肉3%~4%、羊肉5%、猪肉2%[17-18]

IMF区别于其他脂肪组织的显著特点在于含有更多磷脂类物质,磷脂中富含软脂酸、硬脂酸、油酸、亚油酸等[19]。IMF中脂肪酸种类及含量影响肉的色泽:肉中氧合肌红蛋白氧化为高铁肌红蛋白,导致肉由红色转变为褐色,该过程常伴随IMF酸败现象发生,IMF中不饱和脂肪酸含量越高越易发生酸败[20]。多汁性取决于肉中水分含量及咀嚼时分泌的唾液,IMF会刺激唾液分泌,增加多汁性[20-21]。肉的嫩度是指切割时所需的剪切力,是咀嚼时口感好坏的重要指标,决定于肌纤维、结缔组织等含量及结构状态。IMF可切断肌肉纤维束间的交联结构,有利于咀嚼肉质时断裂肌肉纤维,从而改善肉的嫩度[22]。在不同物种中,IMF含量与系水力之间的关系不同:IMF含量与鸡肉系水力呈负相关[23];IMF含量对猪肉系水力无显著影响[24];牛肉大理石花纹等级对牛肉蒸煮损失影响显著,大理石花纹丰富,则IMF含量高,蒸煮损失小[25]

脂肪酸是脂肪中重要的化学物质,分为饱和脂肪酸和不饱和脂肪酸。不饱和脂肪酸包括单不饱和脂肪酸及多不饱和脂肪酸。其中,n-3和n-6多不饱和脂肪酸含量和比例会影响肥胖等疾病发生[26]。多不饱和脂肪酸也是不同肉品独特风味的关键所在[27],多不饱和脂肪酸加热后发生反应,产生醇、酮及酯类化学物质影响肉风味[28],因此脂肪酸种类及数量与肉风味紧密相关。对禽类肌肉脂肪酸组成比例的分析显示,鸡肉中油酸含量最高,其次分别为亚油酸、棕榈酸和硬脂酸;鸭和鹅肉中也是油酸含量最高,其次分别是棕榈酸和亚油酸[29]。对不同品种猪肌肉中脂肪酸含量进行检测,结果显示我国地方品种猪与外来品种猪的脂肪酸组成及含量存在差异[26]。在反刍动物中,IMF中饱和脂肪酸含量为45%~48%,单不饱和脂肪酸含量为35%~45%,多不饱和脂肪酸含量约为5%,肌肉中短链脂肪酸(C4~C10)含量低,中长链脂肪酸(C12~C22)含量高[20]。对羊肉而言,产生香味的主要成分是羰基化合物和不饱和脂肪酸,其中C6~C10脂肪酸是产生膻味的主要物质[20]

3 IMF沉积与营养调控

在动物生长发育过程中,饲料中的营养物质经过消化吸收,主要以肌肉和脂肪存在于体内。动物生长期是IMF形成的关键时间节点,通过营养手段可调控生长期IMF细胞的增殖和分化,促进间充质细胞分化为肌内脂肪前体细胞及IMF中甘油三酯累积[7]。饲粮中粗饲料与精饲料的比例、脂肪和葡萄糖的消化和吸收、饲料中维生素含量、母源营养代谢等均与IMF沉积紧密相关。

3.1 饲粮中粗饲料与精饲料的比例

反刍动物饲粮中,粗饲料是主要的乙酸盐来源,包括玉米秸秆等,精饲料是主要的葡萄糖来源,包括玉米、豆粕等。精饲料中的谷物经瘤胃和小肠吸收后产生挥发性脂肪酸和糖类物质,以此产生能量满足机体需求。饲粮中淀粉含量提高会促进骨骼肌中间充质细胞向脂肪前体细胞分化,增加生长期IMF利用葡萄糖作为脂肪酸从头合成的比例,通过调控IMF中脂肪代谢基因[如过氧化物酶体增殖物激活受体γ(PPARγ)、CCAAT增强子结合蛋白α(C/EBPα)等]表达促进IMF生成[7]。谷物类型及加工处理会影响IMF含量,促进雪花肉形成。与薏米和高粱比,玉米经反刍动物小肠消化产生更多葡萄糖促进IMF形成;与普通碾碎加工方式相比,蒸汽压片处理促进玉米等谷物在瘤胃和小肠中吸收,促进IMF形成[30]。谷物含量较高的饲粮增加动物个体总脂肪含量,也增加IMF含量[31]。研究表明,分别给公牛饲喂“70%精饲料+30%青贮玉米秸秆”和“30%精饲料+70%青贮玉米秸秆”,测定背最长肌和半腱肌中IMF含量,结果显示“70%精料+30%青贮玉米秸秆”组比“30%精料+70%青贮玉米秸秆”组IMF含量要高[32];总消化营养成分相同情况下,“10%粗饲料+90%精饲料”饲喂的育肥和牛IMF含量约为31.7%,而“35%粗饲料+65%精饲料”饲喂的育肥和牛IMF含量在22.9%左右,但2组牛肉中皮下、肠系膜、肌间脂肪含量没有显著差异[33]。给新生牛提前断奶并采用高精料喂养,会激活PPARγ和C/EBPα等通路刺激脂肪前体细胞分化及脂肪沉积,促进牛IMF沉积[34-35]

3.2 脂肪及葡萄糖的消化吸收

甘油三酯摄入、合成及降解之间的平衡影响IMF沉积,甘油三酯的合成是关键因素,甘油三酯的合成需以脂肪酸和甘油为原料。用于合成甘油三酯的脂肪酸主要来源于从头合成及饮食中摄入的脂肪酸,反刍动物的脂肪酸从头合成主要发生在脂肪组织中,人和啮齿类动物脂肪酸从头合成主要发生在肝脏组织中。ATP柠檬酸裂解酶是糖代谢与产生脂肪酸的直接桥梁,是脂肪酸从头合成的关键酶。与皮下脂肪相比,IMF具有更高的ATP柠檬酸裂解酶活性;IMF中高表达葡萄糖转运蛋白,该蛋白负责脂肪组织中葡萄糖的摄入[17]。饮食来源的脂肪酸主要来源于甘油三酯脂蛋白的转运,增加饲粮中油脂含量会影响IMF沉积[31]。甘油三酯合成中所需甘油主要来源于葡萄糖,葡萄糖也是能量的重要来源,因此,增加葡萄糖供给对IMF沉积有重要作用。饲粮中的淀粉在瘤胃中降解为丙酸,丙酸被吸收后进入肝脏,经糖异生途径合成葡萄糖,淀粉进入小肠后在胰腺淀粉酶作用下也分解为葡萄糖。在动物育肥期,增加饲粮中葡萄糖合成所需的丙酸盐含量同样有利于IMF沉积[30, 36]。饲粮中约90%的油脂以脂肪酸形式进入十二指肠而被消化吸收。添加乳化剂可促进高能量高油脂饲粮的消化和吸收促进IMF沉积,胆汁酸可通过脂肪乳化促进脂肪消化和吸收,促进IMF沉积[37]

3.3 饲粮中维生素含量

维生素A、维生素C、维生素D均参与调控IMF形成。在育肥的前期和中期,限制饲粮中维生素A含量或摄入低剂量β-胡萝卜素(维生素A的前体物质)会促进IMF沉积[38]。维生素A抑制脂肪细胞分化,在牛脂肪前体细胞培养中添加维生素A会降低脂肪生成标志物甘油-3-磷酸脱氢酶活性[30];在啮齿类动物中,母鼠饮食中摄入维生素A会促进胎儿脂肪组织的血管生成,提高脂肪祖细胞的密度,也可促进后代小鼠生长[39];维生素A初级代谢产物视黄酸也能够增加人胚胎干细胞中生肌细胞群[40]。维生素C有抗氧化作用,通过抑制细胞外信号调节激酶(ERK)信号通路促进小鼠脂肪前体细胞3T3-L1的成脂分化[41],也能促进绵羊脂肪前体细胞的成脂分化[42];饲粮中加入维生素C可提高牛IMF含量[43-44]。体外细胞试验结果表明维生素D通过抑制PPARγ抑制脂肪细胞生成[45],但相关动物饲喂试验报道较少。维生素D受体(VDR)与PPARγ竞争结合类视黄醇X受体(RXR),高比例的VDR/RXR结合可能降低PPARγ/RXR二聚体形成抑制脂肪发生[30]。与维生素A不同,限制饲粮中维生素D含量不会影响雪花牛肉含量[46]

3.4 母源营养代谢

母体怀孕时期,胎儿获取的营养直接影响其出生后个体的生长发育,脂肪组织的发育和肌肉发育同时发生在胎儿发育的特定时间段内,母源营养状态直接影响胎儿及后代IMF形成[47-48]。反刍动物的脂肪生成起始于妊娠中期,妊娠中期到后期是胎儿脂肪生成的关键阶段,通过调控母源营养可促进间充质细胞分化为脂肪细胞,脂肪细胞数量增长将提高IMF含量,进而促进大理石花纹形成[49-50]。动物出生后,间充质细胞分化来的脂肪-纤维细胞谱系仍存在与基质血管细胞中,作为分化为脂肪细胞的前体细胞,动物的营养及生理状态影响脂肪细胞数量,影响IMF生成[7]。母源营养过剩会导致胎儿和后代个体IMF细胞数量增多[51-52],同时也会提高胶原含量[53];母源营养缺失会减少后代肌肉纤维数量、降低IMF含量,增加整个机体脂肪含量[54]。已有报道称,母源营养状态会通过表观遗传学影响胎儿及后代个体的生长及脂肪组织发育等[30, 55-56]

4 调控IMF沉积的分子机制

IMF沉积受到遗传、饲料成分等因素影响,这些因素最终通过特定的基因网络[如PPARγC/EBPα、锌指蛋白423(ZFP423)、脂肪酸结合蛋白(FABP)4等]及信号通路[如腺苷酸活化蛋白激酶(AMPK)、WNT、促分裂素原活化蛋白激酶(MAPK)等]发挥调控作用(图 1)。

PPARγ:过氧化物酶体增殖物激活受体γ peroxisome proliferators-activated receptor γ;ZFP423:锌指蛋白423 zinc finger protein 423;C/EBPα:CCAAT增强子结合蛋白α CCAAT enhancer binding protein α;FABP4:脂肪酸结合蛋白4 fatty acid binding protein 4;AMPK:腺苷酸活化蛋白激酶AMP-activated protein kinase;MAPK:促分裂素原活化蛋白激酶mitogen-activated protein kinase;FAS:脂肪酸合成酶fatty acid synthetase;ACC:乙酰辅酶A羧化酶acetyl-CoA carboxylase;LPL:脂蛋白脂酶lipoprotein lipase;HSL:激素敏感脂酶hormone-sensitive triglyceride lipase;核受体共激活因子3:NCOA3 nuclear receptor coactivator 3;支链α-酮酸脱氢酶复合体:BCKDHA branched-chain α-ketoacid dehydrogenase complex;钙感应受体:CASR calcium sensing receptor;Krüppel样因子13:KLF13 Krüppel-like factor 13。 图 1 IMF沉积的调控网络 Fig. 1 Regulatory networks of IMF deposition
4.1 调控IMF沉积的关键基因

PPARγ是与甲状腺素相关的核受体家族成员,主要存在于动物白色脂肪组织中,可激活脂蛋白脂酶(LPL)等脂肪细胞标志物表达。C/EBPα是碱性亮氨酸拉链转录因子家族成员。不同因素对IMF沉积的调控通过调控PPARγC/EBPα表达影响IMF脂肪分化。例如,过表达成纤维细胞生长因子21(FGF21)抑制PPARγ等基因表达,调控山羊IMF形成[57];成纤维细胞生长因子10(FGF10)通过促进C/EBPαPPARγ表达促进山羊IMF前体细胞成脂分化[58];过表达DNA甲基转移酶3A(DNMT3A)抑制PPARγ等基因表达,调控猪IMF形成[59];miR-425-5p负调控PPARγFABP4等表达,抑制猪IMF前体细胞成脂分化[60];bta-miR-130a/b通过作用于靶基因PPARγ和细胞色素P450 2U1(CYP2U1)调控牛脂肪前体细胞成脂分化[61]。脂肪细胞分化早期,磷酸化的C/EBPβ与信号传导转录激活因子5A(STAT5A)等转录因子被招募到结合位点,激活PPARγ表达[62]C/EBPα的DNA结合位点存在基因调控区域并具有抑制有丝分裂的作用,C/EBPα的表达可诱导许多脂肪细胞分化的标志物[如FABP4、瘦素(Leptin)、磷酸烯醇式丙酮酸羧激酶(PEPCK)等]的表达。脂肪细胞分化早期阶段C/EBPα开始表达,直接结合PPARγ启动子区域启动PPARγ表达,PPARγ的表达进一步促进C/EBPα表达,形成自我强化的调控循环[63]。脂肪细胞的C/EBPα和PPARγ协调作用将开启脂滴合成等脂肪分化过程[64],C/EBPα与PPARγ共同作用也可诱导非脂肪细胞分化为成熟脂肪细胞。在3T3-L1细胞或成纤维细胞中表达C/EBPα均可诱导这些细胞分化为成熟的脂肪细胞。PPARγ单独作用也可促进脂肪细胞分化,成纤维细胞和间充质细胞中过表达PPARγ会促进细胞分化为白色脂肪细胞,激活PPARγ可诱导脂肪酸结合蛋白等相关蛋白表达[65]

转录调控因子ZFP423是脂肪细胞早期定型分化过程中的重要调控因子,对IMF沉积具有重要作用。ZFP423可促进牛肌肉基质血管细胞分化为脂肪细胞,过表达ZFP423促进成脂分化,同时纤连蛋白表达上调;敲降ZFP423后牛基质血管细胞分化为脂肪细胞的能力减弱[66]。bta-miR-23a直接作用于ZFP423抑制牛肌内纤维-脂肪祖细胞中脂滴积累和脂肪相关基因表达[67]。ZFP423可通过扩大骨形态发生蛋白(BMPs)的效应调控PPARγ的表达而决定白色脂肪生成命运,在小鼠NIH3T3细胞中过表达ZFP423可激活PPARγ表达,促进细胞分化为脂肪细胞;3T3-L1细胞中敲降ZFP423会抑制PPARγ的表达,进而阻碍细胞成脂分化[68]。成年小鼠成熟脂肪细胞中敲除ZFP423的试验结果显示,ZFP423通过抑制早期B-细胞因子2(EBF2)活性抑制已分化白色脂肪细胞中产热基因的表达[69]

FABP是一类同源性较高的胞内蛋白质,在脂肪酸的吸收、转运及代谢过程中发挥重要作用。FABP高亲和力的结合脂肪酸,将脂肪酸从细胞膜转运到脂肪酸氧化位点及其与甘油三酯和磷酸的合成位点,促进脂肪酸摄入及细胞间转运,因此,FABP可通过影响脂肪酸代谢调控IMF含量[70]。在山羊骨骼肌发育过程中,FABP3高表达于60日龄山羊骨骼肌中,90日龄后其表达下调;FABP4在3日龄时表达最低,随后升高至60日龄时达到顶峰。而且,FABP3的转录水平与IMF含量紧密关联,参与调控山羊脂肪沉积和IMF沉积[71]。此外,FABP3和FABP4是调控猪体脂性状的关键基因[72],也是调控雪花牛肉的关键因子[73];在鸡的脂肪细胞中过表达FABP4会促进脂滴积累[74]

脂肪酸的合成与分解与脂肪代谢密切相关,是脂质的必需成分,因此脂肪酸在IMF沉积中具有重要作用。脂肪代谢酶表达量决定动物脂肪沉积量。脂肪酸合成酶(FAS)和乙酰辅酶A羧化酶(ACC)是脂肪酸合成的限速酶。ACC是长链脂肪酸从头合成的限速酶,其活性影响肌肉组织中脂肪代谢。FAS与肌肉和脂肪中脂肪酸含量密切相关,FAS表达量升高,体内甘油三酯含量增加,导致脂肪沉积。在动物育肥阶段,饲喂高能量水平饲粮促进肌肉中FAS表达,提高脂肪含量[75]ACCFAS表达量与牛IMF含量呈正相关,而在禽类动物上,FAS主要在肝脏的脂肪沉积中发挥作用[76]。LPL和激素敏感脂酶(HSL)均是脂肪酸分解相关酶,将甘油三酯水解成非酯化的游离脂肪酸和甘油,在调控脂肪沉积中具有核心作用[77]。LPL产生于脂肪和肌肉组织中,调控甘油三酯的分配,但不同基因型的LPL,其表达量与IMF沉积相关性不同[76]。HSL直接作用于脂肪组织,在不同品种(如哈萨克羊、新疆细毛羊等)中IMF沉积与HSL相关性不同[76]

4.2 调控IMF沉积的信号通路 4.2.1 AMPK信号通路

AMPK是能量代谢调控因子,可促进脂肪酸氧化及脂肪酸合成等生物学过程[78]。AMPK活性与牛IMF含量呈负相关,与牛肌肉发达程度呈正相关[79],说明AMPK调控骨骼肌中间充质细胞的分化,促进其分化成肌肉细胞,而非脂肪细胞。AMPK激活通过磷酸化ACC2促进脂肪氧化,减少甘油三酯合成[80],也可通过FTO基因调控mRNA的m6A去甲基化,调控肌细胞中脂滴聚集[81]。丝氨酸/苏氨酸蛋白激酶(LKB1)激活AMPK下调PPARγC/EBPαFABP4等脂肪细胞标志物,抑制脂肪细胞生成[82],调控肌肉中脂肪代谢及IMF生成[83];沉默调节蛋白5(SIRT5)通过激活AMPK、抑制MAPK途径抑制牛脂肪前体细胞分化及脂肪沉积[84]。一些分子化合物和生物活性物质都会通过AMPK信号通路调节脂肪细胞分化:二甲双胍可通过激活AMPK抑制脂肪分化[85];白藜芦醇[86]、槲皮黄酮[87]和姜黄素[88]过激活AMPK抑制白色脂肪生成,促进脂肪棕色化。

4.2.2 WNT/β-catenin和MAPK信号通路

骨骼肌中WNT/β-catenin通路中β-catenin可调控Pax3和Gli表达,其中Pax3作用于肌肉发生标志物成肌分化蛋白(MyoD),Gli作用于肌肉调控因子生肌因子5(Myf5),进而调控肌肉生成[89-90]。研究母源营养状态对其胎儿影响的相关报道称,母羊营养过剩时,其胎儿骨骼肌中WNT/β-catenin信号通路下调,负调控胎羊肌肉生成,促进脂肪生成[91-92],WNT/β-catenin信号通路主要通过抑制PPARγ和C/EBPα抑制脂肪细胞的分化[93]。在间充质祖细胞中,WNT10b结合卷曲同源物1(FZD1)受体和低密度脂蛋白受体相关蛋白5/6(LRP5/6)受体导致DVL磷酸化和Axin降解,此过程反过来导致β-catenin的低磷酸化,与T细胞因子/淋巴增强因子(TCF/LEF)结合激活WNT通路靶基因,进而抑制脂肪细胞的生成;WNT5a通过刺激MAPK激活Nemo样激酶(NLK)通路,NLK则通过磷酸化组蛋白甲基转移酶SETB1抑制PPARγ表达,抑制脂肪细胞分化[93]。组学研究发现MAPK通路可调控牛IMF沉积[94],对肉鸡肌肉的研究表明脂联素可通过p38 MAPK/激活转录因子2(ATF2)调控IMF沉积[95]

4.2.3 环磷酸腺苷(cAMP)-蛋白激酶A(PKA)信号通路

cAMP-PKA信号通路通过其下游cAMP反应元件结合蛋白(CREB)及其调控转录辅助激活因子(CRTC)发挥作用,肌肉中过表达CRTC2可提高IMF含量及肌纤维横截面积[96]。CRTC3是CRTC家族一员,在能量代谢中发挥重要作用。骨骼肌的中CRTC3影响脂代谢、糖原代谢和线粒体生物合成等生物学过程,肌肉组织中过表达CRTC3可通过促进甘油酰基转移酶的表达而增加肌肉中甘油三酯的含量[97]CRTC3敲除后小鼠脂肪细胞体积变小,脂肪分解能力增强[98]。在3T3-L1细胞分化中,cAMP-PKA信号通路通过激活CREB和C/EBPβ促进脂肪生成[99]

4.2.4 Sonic hedgehog(SHH)信号通路

SHH信号通路通过促进GATA家族成员2(GATA2)表达抵抗脂肪生成,GATA2直接和C/EBPα和PPARγ互作,阻碍PPARγ发挥促脂肪发育作用[100-101],GATA蛋白招募肌细胞增强因子2(MEF2),促进肌肉发生及其他细胞分化[102]。SHH信号通路也可通过核受体超家族成员(NR2F2)负调控脂肪生成,NR2F2结合C/EBPα和PPARγ启动子区抑制其表达[103]

4.3 调控IMF沉积的miRNA

miRNA通过调控与脂肪细胞增殖和分化相关基因的表达,影响IMF沉积。猪IMF细胞中,miR-34a通过ERK通路促进脂肪细胞生成[104];miR-125a-5p作用于Krüppel样因子13(Klf13)抑制IMF前体细胞分化,作用于另一个靶基因长链脂肪酸延伸酶6(Elovl6)影响IMF中脂肪酸的组成[105];miR-17-5p负调控核受体共激活因子3(NCOA3)影响猪IMF生成[106]。牛IMF组学分析结果显示,miR-143等高表达于牛IMF中(与皮下脂肪相比),其靶基因主要参与脂肪代谢及脂肪生成等通路,如MAPK通路[107];miR-27a-5p通过作用于钙感应受体影响IMF沉积[108];bta-miR-23a通过作用于ZFP423协调牛IMF细胞早期定型分化[67]。支链α-酮酸脱氢酶复合体(BCKDHA)可促进绵羊基质血管中脂肪生成,miR-124-3p作用于BCKDHA负调控基质血管中脂肪分化,影响绵羊IMF沉积[109]。此外,研究报道称gga-miR-103-3p及gga-miR-138-2-3p可能参与鸡IMF沉积调控[110]。对啮齿类动物成脂分化研究结果显示,miR-206-3p通过抑制c-Met/PI3K/AKT信号通路抑制3T3-L1细胞分化为脂肪细胞[111];过表达miR-9可通过激活AMPK作用于Patatin样磷脂酶域3(PNPLA3)抑制3T3-L1细胞分化[112];miR-144-3p通过作用于Klf3和羧基末端结合蛋白2(CtBP2)诱导C/EBPα表达,促进小鼠白色脂肪发育[113];miR-93调控Tbx3表达抑制脂肪前体细胞自我更新,通过抑制Sirtuins蛋白家族成员沉默调节蛋白7(SIRT7)表达影响脂肪细胞分化及成熟[114];过表达miR-149-3p或添加类似物可降低骨髓间充质细胞分化为脂肪细胞的潜能[115]

5 小结与展望

综上所述,关于IMF细胞来源、IMF含量与肉品质的关系及调控IMF沉积的分子机制等相关研究已取得较大的进展。然而,IMF沉积调控机制方面亟待深入研究,可着重从以下几个方面展开:第一,IMF沉积关键发育时期及生理生化机制;第二,我国优良家畜品种IMF沉积机制的解析;第三,肉品中肌肉及IMF之间的相互作用及调控概况的探究;第四,对已明确的调控机制,探索出有针对性的改善肉品质方案。总之,多角度探究影响IMF沉积的因素,可为提高肉品质奠定理论基础,也可为改善肉品质提供有效可行的措施,从而促进优质生态产品的生产及发展。

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