猪脂肪发育相关miRNAs的功能研究进展

doi:10.11843/j.issn.0366-6964.2015.12.001

摘要/Abstract

摘要：

脂肪组织与猪肉品质密切相关，是影响猪胴体品质的一大因素。了解猪脂肪组织的生长发育及代谢调控机制，对于畜牧生产及疾病治疗具有重大意义。miRNAs（microRNAs）是一类内源性的、非编码的、长度为18～24 nt的小分子RNA，其主要通过调控基因表达的转录后水平起作用。大量研究表明，miRNAs参与调控脂肪细胞分化、脂肪形成、脂肪酸代谢、胆固醇合成等多个生命过程。然而目前已报道的猪miRNAs仅有326个，且miRNAs调控猪脂肪发育的研究十分欠缺。本文对近年来猪脂肪相关miRNAs的挖掘和鉴定研究工作进行回顾，同时也关注了miRNAs调控猪脂肪发育的研究。

关键词: 猪, 脂肪发育, miRNAs, 调控机制

Abstract:

Adipose tissue，an important factor that affects the porcine carcass quality，is closely related with the pork quality.Understanding the regulation mechanisms of adipose tissue development and fat metabolism are important to the animal husbandry production and disease treatment.miRNAs(microRNAs) are a class of endogenous，non-coding，small RNA molecules，which are typically 18-24 nucleotides(nt) in length.miRNAs play an important role in the regulation of gene expression at the post-transcriptional level.A large number of evidences demonstrated that miRNAs have influence on diverse biological processes，such as preadipocyte differentiation，adipogenesis，fatty acid metabolism and cholesterol biosynthesis.However，only 326 porcine miRNAs has been currently reported and rare studies could be read about the porcine miRNAs that regulate the fat development.Herein，it is reviewed that the studies on the discovery and identification of fat-associated miRNAs in pigs in this paper，and the progress on the research of porcine miRNAs that regulate fat development are also summarized.

Key words: pig, fat development, miRNAs, regulation mechanism

中图分类号:

S828
S813.3

陈晨，胡雄贵，朱吉，任慧波，邓缘，彭英林. 猪脂肪发育相关miRNAs的功能研究进展[J]. 畜牧兽医学报, 2015, 46(12): 2117-2126.

CHEN Chen，HU Xiong-gui，ZHU Ji，REN Hui-bo，DENG Yuan，PENG Ying-lin. Progress on the Research of miRNAs Associated with Fat Development in Pigs[J]. ACTA VETERINARIA ET ZOOTECHNICA SINICA, 2015, 46(12): 2117-2126.

参考文献

［1］KERSHAW E E，FLIER J S.Adipose tissue as an endocrine organ［J］.J Clin Endocrinol Metab，2004，89(6)：2548-2556.
［2］OLLER do NASCIMENTO C M，RIBEIRO E B，OYAMA L M.Metabolism and secretory function of white adipose tissue：effect of dietary fat［J］.An Acad Bras Cienc，2009，81(3)：453-466.
［3］LEFTEROVA M I，LAZAR M A.New developments in adipogenesis［J］.Trends Endocrinol Metab，2009，20(3)：107-114.
［4］WHITE U A，STEPHENS J M.Transcriptional factors that promote formation of white adipose tissue［J］.Mol Cell Endocrinol，2010，318(1-2)：10-14.
［5］LOWE C E，O′RAHILLY S，ROCHFORD J J.Adipogenesis at a glance［J］.J Cell Sci，2011，124(Pt16)：2681-2686.
［6］BUSHATI N，COHEN S M.microRNA functions［J］.Annu Rev Cell Dev Biol，2007，23：175-205.
［7］LEE R C，FEINBAUM R L，AMBROS V.The C.elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14［J］.Cell，1993，75(5)：843-854.
［8］REINHART B J，SLACK F J，BASSON M，et al.The 21-nucleotide let-7 RNA regulates developmental timing in Caenorhabditis elegans［J］.Nature，2000，403(6772)：901-906.
［9］MCGREGOR R A，CHOI M S.microRNAs in the regulation of adipogenesis and obesity［J］.Curr Mol Med，2011，11(4)：304-316.
［10］DOENCH J G，PETERSEN C P，SHARP P A.siRNAs can function as miRNAs［J］.Genes Dev，2003，17(4)：438-442.
［11］LYTLE J R，YARIO T A，STEITZ J A.Target miRNAs are repressed as efficiently by microRNA-binding sites in the 5′ UTR as in the 3′ UTR［J］.Proc Natl Acad Sci U S A，2007，104(23)：9667-9672.
［12］TAY Y，ZHANG J，THOMSON A M，et al.MicroRNAs to Nanog，Oct4 and Sox2 coding regions modulate embryonic stem cell differentiation［J］.Nature，2008，455(7216)：1124-1128.
［13］WERNERSSON R，SCHIERUP M H，JØRGENSEN F G，et al.Pigs in sequence space：a 0.66X coverage pig genome survey based on shotgun sequencing［J］.BMC Genomics，2005，6：70.
［14］KIM H J，CUI X，KIM E J，et al.New porcine microRNA genes found by homology search［J］.Genome，2006，49(10)：1283-1286.
［15］KIM J，CHO I S，HONG J S，et al.Identification and characterization of new microRNAs from pigs［J］.Mamm Genome，2008，19(7-8)：570-580.
［16］CHO I S，KIM J，SEO H Y，et al.Cloning and characterization of microRNAs from porcine skeletal muscle and adipose tissue［J］.Mol Biol Rep，2010，37(7)：3567-3574.
［17］REDDY A M，ZHENG Y，JAGADEESWARAN G，et al.Cloning，characterization and expression analysis of porcine microRNAs［J］.BMC Genomics，2009，10：65.doi：10.1186/1471-2164-10-65.
［18］XIE S S，LI X Y，LIU T，et al.Discovery of procine microRNAs in multiple tissues by a Solexa deep sequencing approach［J］.PLoS One，2011，6(1)：e16235.
［19］ESAU C，KANG X，PERALTA E，et al.MicroRNA-143 regualtes adipocyte differentiation［J］.J Biol Chem，2004，279(50)：52361-52365.
［20］WANG T，LI M，GUAN J，et al.MicroRNAs miR-27a and miR-143 regulate porcine adipocyte lipid metabolism［J］.Int J Mol Sci，2011，12(11)：7950-7959.
［21］CHEN L，HOU J，YE L，et al.MicroRNA-143 regulates adipogenesis by modulating the MAP2K5-ERK5 signaling［J］.Sci Rep，2014，4：3819.doi：10.1038/srep03819.
［22］SUN T，FU M，BOOKOUT A L，et al.MicroRNA let-7 regulates 3T3-L1 adipogenesis［J］.Mol Endocrinol，2009，23(6)：925-931.
［23］CHEN C，AI H，REN J，et al.A global view of porcine transcriptome in three tissues from a full-sib pair with extreme phenotypes in growth and fat deposition by paired-end RNA sequencing［J］.BMC Genomics，2011，12：448.doi：10.1186/1471-2164-12-448.
［24］LI G，LI Y，LI X，et al.MicroRNA identity and abundance in developing swine adipose tissue as determined by Solexa sequencing［J］.J Cell Biochem，2011，112(5)：1318-1328.
［25］ESAU C，DAVIS S，MURRAY S F，et al.miR-122 regulation of lipid metabolism revealed by in vivo antisense targeting［J］.Cell Metab，2006，3(2)：87-98.
［26］CIRERA S，BIRCK M，BUSK P K，et al.Expression profiles of miRNA-122 and its target CAT1 in minipigs(Sus scrofa) fed a high-cholesterol diet［J］.Comp Med，2010，60(2)：136-141.
［27］LI G，WU Z，LI X，et al.Biological role of microRNA-103 based on expression profile and target genes analysis in pigs［J］.Mol Biol Rep，2011，38(7)：4777-4786.
［28］PENG Y，XIANG H，CHEN C，et al.MiR-224 impairs adipocyte early differentiation and regulates fatty acid metabolism［J］.Int J Biochem Cell Biol，2013，45(8)：1585-1593.
［29］CHEN C，DENG B，QIAO M，et al.Solexa sequencing identification of conserved and novel microRNAs in backfat of Large White and Chinese Meishan pigs［J］.PLoS One，2012，7(2)：e31426.
［30］CHEN C，PENG Y，PENG Y，et al.miR-135a-5p inhibits 3T3-L1 adipogenesis through activation of canonical Wnt/β-catenin signaling［J］.J Mol Endocrinol，2014，52(3)：311-320.
［31］CHEN C，XIANG H，PENG Y L，et al.Mature miR-183，negatively regulated by transcription factor GATA3，promotes 3T3-L1 adipogenesis through inhibition of the canonical Wnt/β-catenin signaling pathway by targeting LRP6［J］.Cell Signal，2014，26(6)：1155-1165.
［32］FERNANDEZ X，MONIN G，TALMANT A，et al.Influence of intramuscular fat content on the quality of pig meat-1.Composition of the lipid fraction and sensory characteristics of m.longissimus lumborum［J］.Meat Sci，1999，53(1)：59-65.
［33］VAN LAACK R L，STEVENS S G，STALDER K J.The influence of ultimate pH and intramuscular fat content on pork tenderness and tenderization［J］.J Anim Sci，2001，79(2)：392-397.
［34］GARDAN D，GONDRET F，LOUVEAU I.Lipid metabolism and secretory function of porcine intramuscular adipocytes compared with subcutaneous and perirenal adipocytes［J］.Am J Physiol Endocrinol Metab，2006，291(2)：E372-E380.
［35］ZHOU X，LI D，YIN J，et al.CLA differently regulates adipogenesis in stromal vascular cells from porcine subcutaneous adipose and skeletal muscle［J］.J Lipid Res，2007，48(8)：1701-1709.
［36］GUO Y，MO D，ZHANG Y，et al.MicroRNAome comparison between intramuscular and subcutaneous vascular stem cell adipogenesis［J］.PLoS One，2012，7(9)：e45410.
［37］XU P，VERNOOY S Y，GUO M，et al.The Drosophila microRNA Mir-14 suppresses cell death and is required for normal fat metabolism［J］.Curr Biol，2003，13(9)：790-795.
［38］KRÜTZFELDT J，RAJEWSKY N，BRAICH R，et al.Silencing of microRNAs in vivo with ‘antagomirs’［J］.Nature，2005，438(7068)：685-689.
［39］ILIOPOULOS D，DROSATOS K，HIYAMA Y，et al.MicroRNA-370 controls the expression of microRNA-122 and Cpt1α and affects lipid metabolism［J］.J Lipid Res，2010，51(6)：1513-1523.
［40］宁小敏．miR-196a对猪前脂肪细胞增殖分化的影响［D］．杨凌：西北农林科技大学，2010．
NING X M.Effects of miR-196a on porcine adipocyte proliferation and differentiation［D］.Yangling：Northwest Agriculture & Forestry University，2010.(in Chinese)
［41］ROMAO J M，JIN W，HE M，et al.Altered microRNA expression in bovine subcutaneous and visceral adipose tissue from cattle under different diet［J］.PLoS One，2012，7(7)：e40605.
［42］SURYAWAN A，HU C Y.Effect of retinoic acid on differentiation of cultured pig preadipocytes［J］.J Anim Sci，1997，75(1)：112-117.
［43］BRANDEBOURG T D，HU C Y.Regulation of differentiating pig preadipocytes by retinoic acid［J］.J Anim Sci，2005，83(1)：98-107.
［44］李美航，仇杨，刘帅，等．过表达miR-103促进猪前体脂肪细胞分化［J］．生物工程学报，2012，28(8)：927-936．
LI M H，QIU Y，LIU S，et al.Over-expressed miR-103 promotes porcine adipocyte differentiation［J］.Chinese Journal of Biotechnology，2012，28(8)：927-936.(in Chinese)
［45］KARBIENER M，FISCHER C，NOWITSCH S，et al.microRNA miR-27b impairs human adipocyte differentiation and targets PPARγ［J］.Biochem Biophys Res Commun，2009，390(2)：247-251.
［46］LIN Q，GAO Z，ALARCON R M，et al.A role of miR-27 in the regulation of adipogenesis［J］.FEBS J，2009，276(8)：2348-2358.
［47］KIM S Y，KIM A Y，LEE H W，et al.miR-27a is a negative regulator of adipocyte differentiation via suppressing PPARγ expression［J］.Biochem Biophys Res Commun，2010，392(3)：323-328.
［48］KANG T，LU W，XU W，et al.MicroRNA-27(miR-27) targets prohibitin and impairs adipocyte differentiation and mitochondrial function in human adipose-derived stem cells［J］.J Biol Chem，2013，288(48)：34394-34402.
［49］LIN X，LUO J，ZHANG L P，et al.MiR-27a suppresses triglyceride accumulation and affects gene mRNA expression associated with fat metabolism in dairy goat mammary gland epithelial cells［J］.Gene，2013，521(1)：15-23.
［50］YI C，XIE W D，LI F，et al.MiR-143 enhances adipogenic differentiation of 3T3-L1 cells through targeting the coding region of mouse pleiotrophin［J］.FEBS Lett，2011，585(20)：3303-3309.
［51］KELLER P，GBURCIK V，PETROVIC N，et al.Gene-chip studies of adipogenesis-regulated microRNAs in mouse primary adipocytes and human obesity［J］.BMC Endocr Disord，2011，11：7.
［52］GUO Y，CHEN Y，ZHANG Y，et al.Up-regulated miR-145 expression inhibits porcine preadipocyte differentiation by targeting IRS1［J］.Int J Biol Sci，2012，8(10)：1408-1417.
［53］LI H，CHEN X，GUAN L，et al.MiRNA-181a regulates adipogenesis by targeting tumor necrosis factor-α(TNF-α) in the porcine model［J］.PLoS One，2013，8(10)：e71568.
［54］TANIGUCHI M，NAKAJIMA I，CHIKUNI K，et al.MicroRNA-33b downregulates the differentiation and development of porcine preadipocytes［J］.Mol Biol Rep，2014，41(2)：1081-1090.
［55］NAJAFI-SHOUSHTARI S H，KRISTO F，LI Y，et al.MicroRNA-33 and the SREBP host genes cooperate to control cholesterol homeostasis［J］.Science，2010，328(5985)：1566-1569.
［56］MARQUART T J，ALLEN R M，ORY D S，et al.miR-33 links SREBP-2 induction to repression of sterol transporters［J］.Proc Natl Acad Sci U S A，2010，107(27)：12228-12232.
［57］DÁVALOS A，GOEDEKE L，SMIBERT P，et al.miR-33a/b contribute to the regulation of fatty acid metabolism and insulin signaling［J］.Proc Natl Acad Sci U S A，2011，108(22)：9232-9237.
［58］SHI X E，LI Y F，JIA L，et al.MicroRNA-199a-5p affects porcine preadipocyte proliferation and differentiation［J］.Int J Mol Sci，2014，15(5)：8526-8538.
［59］KAJIMOTO K，NARABA H，IWAI N.MicroRNA and 3T3-L1 pre-adipocyte differentiation［J］.RNA，2006，12(9)：1626-1632.
［60］LAINE S K，ALM J J，VIRTANEN S P，et al.MicroRNAs miR-96，miR-124，and miR-199a regulate gene expression in human bone marrow-derived mesenchymal stem cells［J］.J Cell Biochem，2012，113(8)：2687-2695.
［61］LEE E K，LEE M J，ABDELMOHSEN K，et al.miR-130 suppresses adipogenesis by inhibiting peroxisome proliferator-activated receptor gamma expression［J］.Mol Cell Biol，2011，31(4)：626-638.
［62］PAN S，ZHENG Y，ZHAO R，et al.MicroRNA-130b and microRNA-374b mediate the effect of materal dietary protein on offspring lipid metabolism in Meishan pigs［J］.Br J Nutr，2013，109(10)：1731-1738.
［63］PAN S，YANG X，JIA Y，et al.Microvesicle-shuttled miR-130b reduces fat deposition in recipient primary cultured porcine adipocytes by inhibiting PPAR-γ expression［J］.J Cell Physiol，2014，229(5)：631-639.
［64］PAN S，ZHENG Y，ZHAO R，et al.miRNA-374 regulates dexamethasone-induced differentiation of primary cultures of porcine adipocytes［J］.Horm Metab Res，2013，45(7)：518-525.
［65］LARSEN M O，ROLIN B.Use of the Göttingen minipig as a model of diabetes，with special focus on type 1 diabetes research［J］.ILAR J，2004，45(3)：303-313.
［66］BELLINGER D A，MERRICKS E P，NICHOLS T C.Swine models of type 2 diabetes mellitus：insulin resistance，glucose tolerance，and cardiovascular complications［J］.ILAR J，2006，47(3)：243-258.
［67］LUNNEY J K.Advances in swine biomedical model genomics［J］.Int J Biol Sci，2007，3(3)：179-184.
［68］GORODKIN J，CIRERA S，HEDEGAARD J，et al.Porcine transcriptome analysis based on 97 non-normalized cDNA libraries and assembly of 1，021，891 expressed sequence tags［J］.Genome Biol，2007，8(4)：R45.

[1]	王璟, 滑留帅, 陈俊峰, 张家庆, 任巧玲, 白红杰, 郭红霞, 徐照学, 邢宝松, 白献晓, 曹海. 去势对淮南公猪背最长肌转录组的影响[J]. 畜牧兽医学报, 2019, 50(9): 1746-1758.
[2]	郭晓红, 郭玉龙, 刘亚丹, 刘娟, 史文倩, 董磊, 蔡春波, 曹果清, 李步高, 高鹏飞. 仔猪不同发育阶段结肠微生物菌群特征分析[J]. 畜牧兽医学报, 2019, 50(9): 1759-1774.
[3]	刘国庆, 张丽阳, 马雪莲, 王良治, 刘东元, 邢冠中, 杨柳, 李素芬, 廖秀冬, 吕林, 罗绪刚. 我国畜禽饲料资源中矿物质元素磷含量的调查研究[J]. 畜牧兽医学报, 2019, 50(9): 1841-1848.
[4]	付绍祖, 李露露, 张敬, 李丹, 郑海学. 猪源DDX56对口蹄疫病毒的复制及其对病毒诱导的RLR通路调节的研究[J]. 畜牧兽医学报, 2019, 50(9): 1849-1856.
[5]	王昌英, 鹿红宇, 隋敏敏, 王岩超, 刘根, 孙亿, 姜运良. 猪SERPINC1基因对PCV2复制的效应及其转录调控[J]. 畜牧兽医学报, 2019, 50(8): 1545-1553.
[6]	胡永新, 赵永刚, 张永强, 刘拂晓, 樊晓旭, 吴晓东, 王志亮. 表达非洲猪瘟病毒P72蛋白复制缺陷型重组腺病毒的构建及鉴定[J]. 畜牧兽医学报, 2019, 50(8): 1635-1641.
[7]	侯林杉, 贾敬亮, 顾文源, 刘宝京, 师乾凯, 袁广富, 陈少杰, 范京惠, 左玉柱. 基于猪丁型冠状病毒重组S1蛋白间接ELISA抗体检测方法的建立与应用[J]. 畜牧兽医学报, 2019, 50(8): 1642-1648.
[8]	邱静静, 丁轲, 余祖华, 贾艳艳, 张春杰, 汪洋, 赵战勤. 2014-2017年河南省副猪嗜血杆菌分离菌株的PCR鉴定及分型[J]. 畜牧兽医学报, 2019, 50(8): 1649-1657.
[9]	李志强, 闫书平, 纪晓霞, 王凯, 张源淑. 血管紧张素转换酶2在仔猪空肠中的分布表达及其与物质转运的关系[J]. 畜牧兽医学报, 2019, 50(8): 1676-1684.
[10]	王昌英, 鹿红宇, 隋敏敏, 王岩超, 刘根, 孙亿, 姜运良. 猪SERPINC1基因对PCV2复制的效应及其转录调控[J]. 畜牧兽医学报, 2019, 50(8): 1545-1553.
[11]	胡永新, 赵永刚, 张永强, 刘拂晓, 樊晓旭, 吴晓东, 王志亮. 表达非洲猪瘟病毒P72蛋白复制缺陷型重组腺病毒的构建及鉴定[J]. 畜牧兽医学报, 2019, 50(8): 1635-1641.
[12]	侯林杉, 贾敬亮, 顾文源, 刘宝京, 师乾凯, 袁广富, 陈少杰, 范京惠, 左玉柱. 基于猪丁型冠状病毒重组S1蛋白间接ELISA抗体检测方法的建立与应用[J]. 畜牧兽医学报, 2019, 50(8): 1642-1648.
[13]	邱静静, 丁轲, 余祖华, 贾艳艳, 张春杰, 汪洋, 赵战勤. 2014-2017年河南省副猪嗜血杆菌分离菌株的PCR鉴定及分型[J]. 畜牧兽医学报, 2019, 50(8): 1649-1657.
[14]	李志强, 闫书平, 纪晓霞, 王凯, 张源淑. 血管紧张素转换酶2在仔猪空肠中的分布表达及其与物质转运的关系[J]. 畜牧兽医学报, 2019, 50(8): 1676-1684.
[15]	刘宗立, 陈涛, 杨丹丹, 崔景香, 李川皓, 曾勇庆, 陈伟. 猪Nrf2基因克隆、生物信息学分析及启动子区转录活性分析[J]. 畜牧兽医学报, 2019, 50(7): 1328-1339.