MiR-146a-5p Targeting SMAD4 and TRAF6 Inhibits Adipogenensis Through TGF-β and NF-κB Signal Pathways in Porcine Intramuscular Preadipocytes

Abstract

Background: Intramuscular fat (IMF) content is a vital parameter to assess pork quality. Increasing evidences have shown that microRNAs (miRNAs) play an important role in regulating porcine IMF deposition. Here, a novel miRNA implicated in porcine IMF adipogenesis was found, and its effect and regulatory mechanism was further explored on the proliferation and differentiation of intramuscular preadipocytes.Results: By miRNAs sequencing analysis in porcine adipose tissues, we found that miR-146a-5p was a potential regulator of porcine IMF adipogenesis. Further study showed that miR-146a-5p mimics inhibited the proliferation of porcine intramuscular preadipocytes, but its inhibitor promoted cell proliferation. Interestingly, miR-146a-5p mimics also repressed preadipocyte differentiation, whereas its inhibitor promoted adipogenic differentiation. Mechanistically, miR-146a-5p suppressed cell proliferation by directly targeting SMAD family member 4 (SMAD4) to attenuate the TGF-β signal. Moreover, miR-146a-5p inhibited the differentiation of intramuscular preadipocytes by targeting TNF receptor associated factor 6 (TRAF6) to weaken the NF-κB signaling of the TRAF6 downstream pathway.Conclusions: MiR-146a-5p targeting SMAD4 and TRAF6 inhibited porcine intramuscular adipogenesis through attenuating TGF-β and NF-κB signals, respectively. These findings provided a novel miRNA biomarker for regulating intramuscular adipogenesis to promote pork quality.

Role of microRNAs in myogenesis and their effects on meat quality in pig — A review

“…While the differentiation of adipocytes controlled through targeting tumor necrosis factor ( TNF ) receptor-associated factor 6 ( TRAF6 ) attenuates the nuclear factor kappa beta ( NF-κB ) signaling. This miRNA could also be considered as a biomarker for amending the IM adipogenesis to improve pork quality [ 111 ]. The overexpression of miR-181a promoted the accumulation of lipid droplets, raised the amount of triglycerides, and decreased the TNF-α protein expression in porcine preadipocytes, while the inhibition of this miRNA showed opposite effects [ 112 ].…”