title: Knockdown of both FoxO1 and C/EBPβ promotes adipogenesis in porcine preadipocytes through feedback regulation.
abstract: FoxO1 and C/EBPβ are important transcription factors during adipogenic differentiation; however, the potential mechanisms of their inter-regulation in adipogenesis remain unknown. We found that FoxO1 and C/EBPβ are abundant in adipose tissues of 3- and 180-day pigs at the mRNA and protein levels. During porcine preadipocyte differentiation, C/EBPβ expression increases to the peak at Day 2 and then decreases. In contrast, FoxO1 is lowest on Day 2 and gradually increases. Knockdown of FoxO1 or C/EBPβ with lentivirus-mediated shRNA enhances or inhibits lipid accumulation and adipogenic maker (C/EBPα and aP2) expression, respectively. FoxO1 depletion causes a mild decrease of C/EBPβ protein level, and C/EBPβ interference also inhibits the expression of FoxO1 protein. Knockdown of both FoxO1 and C/EBPβ promotes lipid accumulation at Day 8, and increases the adipogenic markers during differentiation in comparison with the controls and the FoxO1 knockdown alone. Co-immunoprecipitation experiments indicate that FoxO1 binds to C/EBPβ in adipose tissues and in vitro. In conclusion, the results suggest that FoxO1 and C/EBPβ regulate preadipocyte adipogenesis possibly through C/EBPβ → FoxO1 → C/EBPβ feedback regulatory loop and FoxO1-C/EBPβ protein complex.
authors.affiliation: Laboratory of Animal Fat Deposition and Muscle Development, College of Animal Science and Technology, Northwest A&F University, Yangling, China.
authors.forename: Xiong
authors.initials: X
authors.lastname: Yan
authors.forename: Pang
authors.initials: P
authors.lastname: Weijun
authors.forename: Wei
authors.initials: W
authors.lastname: Ning
authors.forename: Wang
authors.initials: W
authors.lastname: Yu
authors.forename: Ren
authors.initials: R
authors.lastname: Wenkai
authors.forename: Yang
authors.initials: Y
authors.lastname: Gongshe
mesh_terms: D017667:Adipocytes / Q000166:cytology / Q000378:metabolism*; D050156:Adipogenesis / Q000235:genetics*; D000273:Adipose Tissue / Q000166:cytology / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn; D001483:Base Sequence; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D002454:Cell Differentiation; D002478:Cells, Cultured; D025461:Feedback, Physiological; D051858:Forkhead Transcription Factors / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D005822:Genetic Vectors; D016086:Lentivirus / Q000235:genetics; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D013552:Swine
chemical_list: D022782:CCAAT-Enhancer-Binding Protein-beta; D051858:Forkhead Transcription Factors; D012333:RNA, Messenger; D034741:RNA, Small Interfering
keywords: C/EBPβ; FoxO1; adipogenesis; pig; preadipocyte