期刊文献

SIRT5 Regulates Lipid Deposition in Goat Preadipocytes via PI3K-Akt and MAPK Signaling Pathways 收藏

SIRT5通过PI3K-AKT和MAPK信号传导途径调节山羊前脂肪细胞中的脂质沉积
原文求助 发布源
作者
Haiyang Li [1];Wenli Yao [2];Changheng Yang (https://orcid.org/0000-0003-3968-4377) [3];Wenyang Zhang [4];Yong Wang [5];Yaqiu Lin [6];Zhanyu Du (https://orcid.org/0000-0001-5880-8537) [7];Changhui Zhang [8];Lian Huang [9];Ming Zhang [10];Huaigong Fan [11];Jiangjiang Zhu [12];Hua Xiang [13];
作者单位
[1]Qinghai-Tibetan Plateau Animal Genetic Resource Reservation and Utilization Key Laboratory of Sichuan Province, Southwest Minzu University, Chengdu 610041, China; [2]Qinghai-Tibetan Plateau Animal Genetic Resource Reservation and Utilization Key Laboratory of Sichuan Province, Southwest Minzu University, Chengdu 610041, China; [3]Qinghai-Tibetan Plateau Animal Genetic Resource Reservation and Utilization Key Laboratory of Sichuan Province, Southwest Minzu University, Chengdu 610041, China; [4]Qinghai-Tibetan Plateau Animal Genetic Resource Reservation and Utilization Key Laboratory of Sichuan Province, Southwest Minzu University, Chengdu 610041, China; [5]Qinghai-Tibetan Plateau Animal Genetic Resource Reservation and Utilization Key Laboratory of Sichuan Province, Southwest Minzu University, Chengdu 610041, China; [6]Qinghai-Tibetan Plateau Animal Genetic Resource Reservation and Utilization Key Laboratory of Sichuan Province, Southwest Minzu University, Chengdu 610041, China; [7]Qinghai-Tibetan Plateau Animal Genetic Resource Reservation and Utilization Key Laboratory of Sichuan Province, Southwest Minzu University, Chengdu 610041, China; [8]Qinghai-Tibetan Plateau Animal Genetic Resource Reservation and Utilization Key Laboratory of Sichuan Province, Southwest Minzu University, Chengdu 610041, China; [9]Qinghai-Tibetan Plateau Animal Genetic Resource Reservation and Utilization Key Laboratory of Sichuan Province, Southwest Minzu University, Chengdu 610041, China; [10]Qinghai-Tibetan Plateau Animal Genetic Resource Reservation and Utilization Key Laboratory of Sichuan Province, Southwest Minzu University, Chengdu 610041, China; [11]Sichuan Guonong Tianfu Agricultural Development Co., Ltd., Chengdu 611441, China; [12]Qinghai-Tibetan Plateau Animal Genetic Resource Reservation and Utilization Key Laboratory of Sichuan Province, Southwest Minzu University, Chengdu 610041, China; [13]Qinghai-Tibetan Plateau Animal Genetic Resource Reservation and Utilization Key Laboratory of Sichuan Province, Southwest Minzu University, Chengdu 610041, China;
发布日期
2025-4-7
页码
1072
DOI
10.3390/ani15071072
来源信息
Animals ISSN：2076-2615, 2025年, 15卷, 7期, 1072页
摘要
Silent Information Regulator 5 (SIRT5) has been established as a crucial regulator of cellular alanylation modification. Furthermore, accumulating evidence suggests that SIRT5 plays a significant regulatory role in key metabolic pathways, including glycolysis, the tricarboxylic acid (TCA) cycle, and fatty acid oxidation, all of which are closely associated with cellular lipid metabolism. Despite these advancements, the specific role of SIRT5 in regulating intramuscular fat (IMF) deposition in goats, as well as the underlying molecular mechanisms, remains largely unexplored. In this study, we cloned the complete coding sequence of the goat SIRT5 gene and, through amino acid sequence alignment, demonstrated its closest phylogenetic relationship with sheep. Additionally, we characterized the higher expression of SIRT5 during the differentiation of goat intramuscular precursor adipocytes. The silencing of SIRT5 by siRNA-mediated knockdown significantly upregulated the expression of lipogenesis-related genes and enhanced lipid deposition in goat intramuscular preadipocytes. Concurrently, SIRT5 deficiency led to the inhibition of cell proliferation and a marked reduction in apoptosis. Interestingly, although overexpression of SIRT5 promoted cell proliferation, it did not significantly alter lipid deposition in goat intramuscular precursor adipocytes. RNA sequencing (RNA-seq) analysis identified a total of 106 differentially expressed genes (DEGs) following SIRT5 silencing in goat preadipocytes, predominantly involved in the Focal adhesion, HIF-1, PI3K-Akt, and MAPK signaling pathways by KEGG pathway enrichment analysis. Notably, we successfully reversed the phenotypic effects observed in SIRT5 knockdown goat precursor adipocytes by inhibiting the PI3K-Akt and MAPK signaling pathways using the AKT inhibitor LY294002 and the p38 MAPK pathway inhibitor PD169316, respectively. In conclusion, our findings demonstrated that SIRT5 may modulate intramuscular fat deposition in goats through PI3k-Akt and MAPK signaling pathways. These results expand the gene regulatory network associated with IMF formation and provide a theoretical foundation for improving meat quality by targeting IMF deposition.
摘要译文
无声信息调节剂5（SIRT5）已被确定为细胞丙烷化修饰的关键调节剂。此外，积累的证据表明，SIRT5在关键代谢途径中起着重要的调节作用，包括糖酵解，三羧酸（TCA）周期和脂肪酸氧化，所有这些都与细胞脂质代谢密切相关。尽管有这些进步，但SIRT5在调节山羊肌内脂肪（IMF）沉积以及基本分子机制中的特定作用仍然在很大程度上没有探索。在这项研究中，我们克隆了山羊SIRT5基因的完整编码序列，并通过氨基酸序列比对证明了其与绵羊最接近的系统发育关系。此外，我们表征了山羊肌内前体脂肪细胞分化过程中SIRT5的较高表达。siRNA介导的敲低对SIRT5的沉默显着上调了脂肪生成相关基因的表达和山羊肌内前脂肪细胞中脂质沉积的增强。同时，SIRT5缺乏导致细胞增殖的抑制和明显的凋亡减少。有趣的是，尽管SIRT5的过表达促进了细胞增殖，但并未显着改变山羊肌内前体脂肪细胞中的脂质沉积。RNA测序（RNA-SEQ）分析在山羊前脂肪细胞中SIRT5沉默后总共确定了106个差异表达的基因（DEG），主要参与了局灶性粘附，HIF-1，PI3K-AKT和MAPK信号通路通过KEGG途径富集分析。值得注意的是，我们通过使用AKT抑制剂LY294002和P38 MAPK途径抑制剂PD169316抑制PI3K-AKT和MAPK信号通路，成功地逆转了SIRT5敲低山羊前体脂肪细胞中观察到的表型效应。总之，我们的发现表明SIRT5可以通过PI3K-AKT和MAPK信号通路调节山羊的肌内脂肪沉积。这些结果扩大了与IMF形成相关的基因调节网络，并通过靶向IMF沉积为提高肉质质量提供了理论基础。
Haiyang Li [1];Wenli Yao [2];Changheng Yang (https://orcid.org/0000-0003-3968-4377) [3];Wenyang Zhang [4];Yong Wang [5];Yaqiu Lin [6];Zhanyu Du (https://orcid.org/0000-0001-5880-8537) [7];Changhui Zhang [8];Lian Huang [9];Ming Zhang [10];Huaigong Fan [11];Jiangjiang Zhu [12];Hua Xiang [13];. SIRT5 Regulates Lipid Deposition in Goat Preadipocytes via PI3K-Akt and MAPK Signaling Pathways[J]. Animals, 2025,15(7): 1072