Graugnard Daniel E, Piantoni Paola, Bionaz Massimo, Berger Larry L, Faulkner Dan B, Loor Juan J
Mammalian NutriPhysioGenomics, Department of Animal Sciences, University of Illinois, Urbana, Illinois, 61801, USA.
BMC Genomics. 2009 Mar 31;10:142. doi: 10.1186/1471-2164-10-142.
Transcriptional networks coordinate adipocyte differentiation and energy metabolism in rodents. The level of fiber and starch in diets with adequate energy content fed to young cattle has the potential to alter intramuscular adipose tissue development in skeletal muscle. Post-weaning alterations in gene expression networks driving adipogenesis, lipid filling, and intracellular energy metabolism provide a means to evaluate long-term effects of nutrition on longissimus muscle development across cattle types.
Longissimus lumborum (LL) from Angus (n = 6) and Angus x Simmental (A x S; n = 6) steer calves (155 +/- 10 days age) fed isonitrogenous high-starch (HiS; 1.43 Mcal/kg diet dry matter; n = 6) or low-starch (LoS; 1.19 Mcal/kg diet dry matter; n = 6) diets was biopsied at 0, 56, and 112 days of feeding for transcript profiling of 31 genes associated with aspects of adipogenesis and energy metabolism. Intake of dietary energy (9.44 +/- 0.57 Mcal/d) across groups during the study did not differ but feed efficiency (weight gain/feed intake) during the first 56 days was greater for steers fed HiS. Expression of PPARG increased ca. 2-fold by day 56 primarily due to HiS in A x S steers. Several potential PPARG-target genes (e.g., ACACA, FASN, FABP4, SCD) increased 2.5-to-25-fold by day 56 across all groups, with responses (e.g., FASN, FABP4) being less pronounced in A x S steers fed LoS. This latter group of steers had markedly greater blood plasma glucose (0.99 vs. 0.79 g/L) and insulin (2.95 vs. 1.17 microg/L) by day 112, all of which were suggestive of insulin resistance. Interactions were observed for FABP4, FASN, GPAM, SCD, and DGAT2, such that feeding A x S steers high-starch and Angus steers low-starch resulted in greater fold-changes by day 56 or 112 (GPAM). Marked up-regulation of INSIG1 (4-to-8-fold) occurred throughout the study across all groups. SREBF1 expression, however, was only greater on day 112 namely due to LoS in A x S steers. The lipogenic transcription factor THRSP was 6-to-60-fold greater by day 56 primarily due to HiS in A x S steers, constituting the greatest response among all genes.
Results involving gene markers of mature adipocytes (e.g., PPARG, THRSP, SCD) provided evidence of intramuscular adipose tissue differentiation during the early portion of the growing phase. The resulting gene networks underscored a central role for PPARG in controlling transcription of genes which are known to co-ordinately regulate adipocyte differentiation and lipid filling in non-ruminants. Unlike rodents, INSIG1 appears to play an important role in cattle muscle adipogenesis. We propose that a network of transcription regulators and nuclear receptors including PPARG-target genes, INSIG1, and THRSP, coordinate activation of adipocyte differentiation and lipid filling at an early age.
转录网络协调啮齿动物的脂肪细胞分化和能量代谢。给幼牛饲喂能量含量充足的日粮时,日粮中纤维和淀粉的水平有可能改变骨骼肌中肌内脂肪组织的发育。断奶后驱动脂肪生成、脂质填充和细胞内能量代谢的基因表达网络的变化提供了一种手段,用于评估营养对不同类型牛的背最长肌发育的长期影响。
对安格斯牛(n = 6)和安格斯×西门塔尔牛(A×S;n = 6)的阉牛犊(155±10日龄)饲喂等氮高淀粉(HiS;1.43兆卡/千克日粮干物质;n = 6)或低淀粉(LoS;1.19兆卡/千克日粮干物质;n = 6)日粮,在饲喂的第0、56和112天对腰大肌(LL)进行活检,以分析31个与脂肪生成和能量代谢相关基因的转录谱。研究期间各实验组的日粮能量摄入量(9.44±0.57兆卡/天)无差异,但在最初的56天里,饲喂HiS日粮的阉牛犊饲料效率(体重增加/采食量)更高。到第56天时,PPARG的表达增加了约2倍,主要是由于A×S阉牛犊饲喂HiS日粮所致。到第56天时,几个潜在的PPARG靶基因(如ACACA、FASN、FABP4、SCD)在所有组中增加了2.5至25倍,在饲喂LoS日粮的A×S阉牛犊中,这些基因的反应(如FASN、FABP4)不太明显。到第112天时,后一组阉牛的血浆葡萄糖(0.99对0.79克/升)和胰岛素(2.95对1.17微克/升)明显更高,所有这些都提示存在胰岛素抵抗。观察到FABP4、FASN、GPAM、SCD和DGAT2存在相互作用,因此给A×S阉牛饲喂高淀粉日粮、给安格斯阉牛饲喂低淀粉日粮,到第56天或112天时(GPAM)倍数变化更大。在整个研究期间,所有组的INSIG1均出现明显上调(4至8倍)。然而,SREBF1的表达仅在第112天时更高,这主要是由于A×S阉牛犊饲喂LoS日粮所致。到第56天时,生脂转录因子THRSP增加了6至60倍,主要是由于A×S阉牛犊饲喂HiS日粮所致,是所有基因中反应最大者。
涉及成熟脂肪细胞基因标志物(如PPARG、THRSP、SCD)的结果提供了生长阶段早期肌内脂肪组织分化的证据。由此产生的基因网络强调了PPARG在控制已知在非反刍动物中协同调节脂肪细胞分化和脂质填充的基因转录方面的核心作用。与啮齿动物不同,INSIG1似乎在牛肌肉脂肪生成中起重要作用。我们提出,包括PPARG靶基因、INSIG1和THRSP在内的转录调节因子和核受体网络在幼年时协调脂肪细胞分化和脂质填充的激活。