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FOXO1 regulates the formation of bovine fat by targeting CD36 and STEAP4

文献类型： 外文期刊

作者： Song, Yaping 1 ; Zhang, Jiupan 3 ; Jiang, Chao 1 ; Song, Xiaoyu 1 ; Wu, Hao 1 ; Zhang, Juan 1 ; Raza, Sayed Haidar Abbas 4 ; Zhang, Le 5 ; Zhang, Lingkai 1 ; Cai, Bei 1 ; Wang, Xingping 1 ; Reng, Zhuoma Luo 1 ; Ma, Yun 1 ; Wei, Dawei 1 ;

作者机构： 1.Ningxia Univ, Coll Anim Sci & Technol, Yinchuan 750021, Peoples R China

2.Key Lab Ruminant Mol Cell Breeding, Ningxia Hui Autonomous Reg, Yinchuan 750021, Peoples R China

3.Ningxia Acad Agr & Forestry Sci, Inst Anim Sci, Yinchuan 750021, Peoples R China

4.South China Agr Univ, Res Ctr Machining & Safety Livestock & Poultry Pro, Guangzhou 510642, Peoples R China

5.Yanan Univ, Inst Phys Educ, Yanan 716000, Shaanxi, Peoples R China

关键词： Bovine; FOXO1; Adipocytes; RNA-seq; Metabolome

期刊名称：INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES （ 影响因子：8.2； 五年影响因子：7.8 ）

ISSN： 0141-8130

年卷期： 2023 年 248 卷

页码：

收录情况： SCI

摘要： Intramuscular fat content is closely related to the quality of beef, where the forkhead box protein O1 (FOXO1) is involved in adipocyte differentiation and lipid metabolism, but the specific mechanism of its involvement is still unclear. In this study, interfering with FOXO1 promoted the G1/S transformation of bovine adipocytes by enhancing the expression of proliferation marker genes PCNA, CDK1, CDK2, CCNA2, CCNB1, and CCNE2, thereby positively regulating the proliferation of bovine adipocytes. Additionally, interfering with FOXO1 negatively regulated the expression of adipogenic differentiation marker genes PPARG and CEBPA, as well as lipid anabolism marker genes ACC, FASN, SCD1, SREBP1, FABP4, ACSL1, LPL, and DGAT1, thus reducing triglyceride (TG) content and inhibiting the generation of lipid droplets in bovine adipocytes. A combination of transcriptomic and metabolomics analyses revealed that FOXO1 could regulate the lipogenesis of cattle by influencing the AMPK and PI3K/AKT pathways. Importantly, chromatin immunoprecipitation (ChIP) and site directed mutagenesis revealed that FOXO1 could regulate bovine lipogenesis by binding to the promoter regions of the CD36 and STEAP4 genes and affecting their transcriptional activities. These results provide a foundation for studying the role and molecular mechanism of FOXO1 in the bovine adipogenesis.

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