SESN3 Inhibited SMAD3 to Relieve Its Suppression for MiR-124, Thus Regulating Pre-Adipocyte Adipogenesis

Abstract

Sestrin-3, together with the other two members Sestrin-1 and Sestrin-2, belongs to the Sestrin family. The Sestrin protein family has been demonstrated to be involved in antioxidative, metabolic homeostasis, and even the development of nonalcoholic steatohepatitis (NASH). However, the adipogenic regulatory role of SESN3 in adipogenesis still needs to be further explored. In this study, we demonstrated SESN3 inhibited porcine pre-adipocyte proliferation, thus suppressing its adipogenesis. Meanwhile, SESN3 has been demonstrated to inhibit Smad3 thus protecting against NASH. Further, for our previous study, we found mmu-miR-124 involved in 3T3-L1 cell adipogenesis regulation. In this study, we also identified that ssc-miR-124 inhibited porcine pre-adipocyte proliferation, thus suppressing its adipogenesis, and the SMAD3 was an inhibitor of ssc-miR-124 by binding to its promoter. Furthermore, the ssc-miR-124 targeted porcine C/EBPα and GR and thus inhibited pre-adipocyte adipogenesis. In conclusion, SESN3 inhibited SMAD3, thus improving ssc-miR124, and then suppressed C/EBPα and GR to regulate pre-adipocytes adipogenesis.

A genome-wide landscape of mRNAs, lncRNAs, circRNAs and miRNAs during intramuscular adipogenesis in cattle

“…More importantly, our results revealed several potential ceRNA regulatory networks during bovine intramuscular preadipocyte differentiation. Among them, multiple studies have reported that SESN3, FOXO1, GPAM, and miR-27b regulate adipocyte differentiation and lipid metabolism [23][24][25][26]. Furthermore, the expression levels of SESN3, PELI2, GPAM and FOXO1 have been found to be regulated by the competitive binding of lncRNAs/ circRNAs and miRNAs in adipogenesis or other biological processes [23,[54][55][56][57][58].…”

“…Among them, multiple studies have reported that SESN3, FOXO1, GPAM, and miR-27b regulate adipocyte differentiation and lipid metabolism [23][24][25][26]. Furthermore, the expression levels of SESN3, PELI2, GPAM and FOXO1 have been found to be regulated by the competitive binding of lncRNAs/ circRNAs and miRNAs in adipogenesis or other biological processes [23,[54][55][56][57][58]. Finally, we further verified the expression of the genes in the ceRNA network by qRT-PCR, which demonstrated the reliability of the sequencing results in this study.…”

“…The network contains 24 ceRNA axes, consisting of 4 mRNAs, 10 circRNAs, 10 lncRNAs and 7 miRNAs. Among them, SESN3, FOXO1, GPAM, and miR-27b were all related to lipid storage, activation of MAPK activity and fat cell differentiation [23][24][25][26], suggesting that the screened circRNAs/lncRNAs/miRNAs may play important roles in regulating adipogenesis (Fig. 7).…”