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

Int J Biol Macromol

College of Animal Science and Technology, Ningxia University, Yinchuan 750021, China; Key Laboratory of Ruminant Molecular Cell Breeding, Ningxia Hui Autonomous Region, Yinchuan 750021, China. Electronic address:

Published: September 2023

AI Article Synopsis

  • Intramuscular fat content impacts beef quality, and the protein FOXO1 plays a critical role in fat cell development and lipid metabolism, although its exact function was unclear prior to this study.
  • The research showed that inhibiting FOXO1 led to increased bovine fat cell growth and reduced fat cell differentiation by promoting specific genes linked to cell proliferation and negatively affecting genes responsible for fat formation.
  • By using advanced analyses, the study demonstrated that FOXO1 influences fat production in cattle through key cellular pathways (AMPK and PI3K/AKT) and interacts with specific gene promoters (CD36 and STEAP4), paving the way for deeper exploration of how FOXO1 contributes to fat development in cattle.

Article Abstract

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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http://dx.doi.org/10.1016/j.ijbiomac.2023.126025DOI Listing

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