过氧化物酶体增殖物激活受体γ的激活以及长链脂肪酸在不同程度上改变了牛乳腺上皮细胞中的脂肪生成基因网络。
Peroxisome proliferator-activated receptor-gamma activation and long-chain fatty acids alter lipogenic gene networks in bovine mammary epithelial cells to various extents.
作者信息
Kadegowda A K G, Bionaz M, Piperova L S, Erdman R A, Loor J J
机构信息
Department of Animal and Avian Sciences, University of Maryland, College Park, Maryland 20742, USA.
出版信息
J Dairy Sci. 2009 Sep;92(9):4276-89. doi: 10.3168/jds.2008-1932.
Several long-chain fatty acids (LCFA) are natural ligands of nonruminant peroxisome proliferator-activated receptor-gamma (PPARG), which, along with its lipogenic target genes, is upregulated in bovine mammary tissue during lactation. Thus, PPARG might represent an important control point of bovine milk fat synthesis. We tested lipogenic gene network expression via quantitative PCR of 19 genes in bovine mammary epithelial cells cultured with 16:0, 18:0, cis-9 18:1, trans-10 18:1, trans-10,cis-12 18:2 [t10c12 conjugated linoleic acid (CLA)], 20:5, ethanol (control), and the PPARG agonist rosiglitazone (ROSI). Triplicate cultures were maintained for 12 h with 50 muM ROSI or 100 muM LCFA. Responses common to 16:0 and 18:0 relative to the control included significantly greater expression of INSIG1 (+298%, +92%), AGPAT6 (+137%, +169%), FABP3 (+755%, +338%), and FABP4 (+171%, 157%). These were coupled with greater intracellular lipid droplet formation and mRNA of ACSS2, LPIN1, SCD, and SREBF2 in response to 16:0, and greater DGAT1 and THRSP with 18:0. Trans-10 18:1 and t10c12 CLA reduced expression of FASN (-60%, -31%), SCD (-100%, -357%), and SREBF1 (-49%, -189%). Furthermore, t10c12 CLA downregulated ACSS2, FABP3, INSIG1, SREBF2, and THRSP expression. Expression of SREBF1 was lower with cis-9 18:1 (-140%) and 20:5 (-125%) compared with the control. This latter LCFA also decreased SCD, SREBF2, and LPL expression. No effects of LCFA or ROSI on PPARG were observed, but ROSI upregulated (+39% to +269%) expression of ACACA, FASN, LPIN1, AGPAT6, DGAT1, SREBF1, SREBF2, and INSIG1. Thus, these genes are putative PPARG target genes in bovine mammary cells. This is the first report showing a direct effect of trans-10 18:1 on bovine mammary cell lipogenic gene expression. The coordinated upregulation of lipogenic gene networks in response to ROSI and saturated LCFA offers support for PPARG activation in regulating bovine milk fat synthesis.
几种长链脂肪酸（LCFA）是非反刍动物过氧化物酶体增殖物激活受体γ（PPARG）的天然配体，PPARG及其生脂靶基因在泌乳期的牛乳腺组织中上调。因此，PPARG可能是牛乳脂肪合成的一个重要控制点。我们通过定量PCR检测了用16:0、18:0、顺式-9 18:1、反式-10 18:1、反式-10,顺式-12 18:2[反式-10,顺式-12共轭亚油酸（CLA）]、20:5、乙醇（对照）和PPARG激动剂罗格列酮（ROSI）培养的牛乳腺上皮细胞中19个基因的生脂基因网络表达。将三份重复培养物分别用50μM ROSI或100μM LCFA维持12小时。与对照相比，16:0和18:0共同的反应包括INSIG1（分别增加298%、92%）、AGPAT6（分别增加137%、169%）、FABP3（分别增加755%、338%）和FABP4（分别增加171%、157%）的表达显著增加。这些伴随着细胞内脂质滴形成增加以及ACSS2、LPIN1、SCD和SREBF2的mRNA增加（对16:0的反应），以及DGAT1和THRSP增加（对18:0的反应）。反式-10 18:1和反式-10,顺式-12 CLA降低了FASN（分别降低60%、31%）、SCD（分别降低100%、357%）和SREBF1（分别降低49%、189%）的表达。此外，反式-10,顺式-12 CLA下调了ACSS2、FABP3、INSIG1、SREBF及THRSP的表达。与对照相比，顺式-9 18:1（降低140%）和20:5（降低125%）时SREBF1的表达较低。后一种LCFA还降低了SCD、SREBF2和LPL的表达。未观察到LCFA或ROSI对PPARG有影响，但ROSI上调了ACACA（增加39%至269%）、FASN、LPIN1、AGPAT6、DGAT1、SREBF1、SREBF2和INSIG1的表达。因此，这些基因是牛乳腺细胞中假定的PPARG靶基因。这是首次报道反式-10 18:1对牛乳腺细胞生脂基因表达有直接影响。生脂基因网络对ROSI和饱和LCFA的协同上调为PPARG激活在调节牛乳脂肪合成中的作用提供了支持。
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