Hu Rui, Shah Ali Mujtaba, Han Qiang, Ma Jian, Dai Peng, Meng Yukun, Peng Quanhui, Jiang Yahui, Kong Xiangying, Wang Zhisheng, Zou Huawei
Low Carbon Breeding Cattle and Safety Production University Key Laboratory of Sichuan Province, Animal Nutrition Institute, Sichuan Agricultural University, Chengdu 611130, China.
College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130, China.
Animals (Basel). 2024 Apr 22;14(8):1243. doi: 10.3390/ani14081243.
Growth-retarded yaks are of a high proportion on the Tibetan plateau and reduce the economic income of farmers. Our previous studies discovered a maldevelopment in the ruminal epithelium of growth-retarded yaks, but the molecular mechanisms are still unclear. This study aimed to reveal how the proteomic profile in the ruminal epithelium contributed to the growth retardation of yaks. The proteome of the ruminal epithelium was detected using a high-resolution mass spectrometer. There were 52 proteins significantly differently expressed between the ruminal epithelium of growth-retarded yaks and growth-normal yaks, with 32 downregulated and 20 upregulated in growth-retarded yaks. Functional analysis showed the differently expressed proteins involved in the synthesis and degradation of ketone bodies ( = 0.012), propanoate metabolism ( = 0.018), pyruvate metabolism ( = 0.020), and mineral absorption ( = 0.024). The protein expressions of SLC26A3 and FTH1, enriched in the mineral absorption, were significantly downregulated in growth-retarded yaks. The key enzymes ACAT2 and HMGCS2 enriched in ketone bodies synthesis and key enzyme PCCA enriched in propanoate metabolism had lower protein expressions in the ruminal epithelium of growth-retarded yaks. The ATP concentration and relative mitochondrial DNA copy number in the ruminal epithelium of growth-normal yaks were dramatically higher than those of growth-retarded yaks ( < 0.05). The activities of citrate synthase (CS), the α-ketoglutarate dehydrogenase complex (α-KGDHC), isocitrate dehydrogenase (ICD) in the tricarboxylic acid cycle (TCA), and the mitochondrial respiratory chain complex (MRCC) were significantly decreased in ruminal epithelium of growth-retarded yaks compared to growth-normal yaks ( < 0.05). The mRNA expressions of , , and , which are the encoding genes in MRCC I, IV and anaerobic respiration, were also significantly decreased in the ruminal epithelium of growth-retarded yaks ( < 0.05). Correlation analysis revealed that the average daily gain (ADG) was significantly positively correlated to the relative mitochondrial DNA copy number ( < 0.01, r = 0.772) and ATP concentration ( < 0.01, r = 0.728) in the ruminal epithelium, respectively. The ruminal weight was positively correlated to the relative mitochondrial DNA copy number ( < 0.05, r = 0.631) and ATP concentration in ruminal epithelium ( < 0.01, r = 0.957), respectively. The ruminal papillae had a significant positive correlation with ATP concentration in ruminal epithelium ( < 0.01, r = 0.770). These results suggested that growth-retarded yaks had a lower VFA metabolism, ketone bodies synthesis, ion absorption, and ATP synthesis in the ruminal epithelium; it also indicated that the growth retardation of yaks is related to the obstruction of cellular ATP synthesis in rumen epithelial cells.
生长发育迟缓的牦牛在青藏高原上占比很高，这降低了农牧民的经济收入。我们之前的研究发现生长发育迟缓的牦牛瘤胃上皮存在发育不良的情况，但分子机制仍不清楚。本研究旨在揭示瘤胃上皮中的蛋白质组学特征是如何导致牦牛生长发育迟缓的。使用高分辨率质谱仪检测瘤胃上皮的蛋白质组。生长发育迟缓的牦牛与生长正常的牦牛的瘤胃上皮之间有52种蛋白质表达存在显著差异，其中生长发育迟缓的牦牛中有32种下调，20种上调。功能分析表明，差异表达的蛋白质参与酮体的合成与降解（P = 0.012）、丙酸代谢（P = 0.018）、丙酮酸代谢（P = 0.020）和矿物质吸收（P = 0.024）。在矿物质吸收过程中富集的SLC26A3和FTH1的蛋白质表达在生长发育迟缓的牦牛中显著下调。在生长发育迟缓的牦牛瘤胃上皮中，酮体合成过程中富集的关键酶ACAT2和HMGCS2以及丙酸代谢过程中富集的关键酶PCCA的蛋白质表达较低。生长正常的牦牛瘤胃上皮中的ATP浓度和相对线粒体DNA拷贝数显著高于生长发育迟缓的牦牛（P < 0.05）。与生长正常牦牛相比，生长发育迟缓的牦牛瘤胃上皮中三羧酸循环（TCA）中的柠檬酸合酶（CS）、α-酮戊二酸脱氢酶复合体（α-KGDHC）、异柠檬酸脱氢酶（ICD）以及线粒体呼吸链复合体（MRCC）的活性显著降低（P < 0.05）。MRCC I、IV以及无氧呼吸的编码基因ND1、ND4和LDHA的mRNA表达在生长发育迟缓的牦牛瘤胃上皮中也显著降低（P < 0.05）。相关性分析表明，平均日增重（ADG）分别与瘤胃上皮中的相对线粒体DNA拷贝数（P < 0.01，r = 0.772）和ATP浓度（P < 0.01，r = 0.728）显著正相关。瘤胃重量分别与瘤胃上皮中的相对线粒体DNA拷贝数（P < 0.05，r = 0.631）和ATP浓度（P < 0.01，r = 0.957）正相关。瘤胃乳头与瘤胃上皮中的ATP浓度显著正相关（P < 0.01，r = 0.770）。这些结果表明，生长发育迟缓的牦牛瘤胃上皮中的挥发性脂肪酸代谢、酮体合成、离子吸收和ATP合成较低；这也表明牦牛的生长发育迟缓与瘤胃上皮细胞中细胞ATP合成受阻有关。
