SGK1 Affects the Phosphorylation of FOXO1/FOXO3 Promoting Bovine Fat Deposition via the PI3K/Akt Signaling Pathway

Abstract Background : Improving the intramuscular fat content of beef not only could improve our living standard, but decrease the the risk of the disease from the aspect of human nutrition and diet. Serum/glucocorticoid-inducible kinase 1 (SGK1) is a critical kinase involved in regulating multiple metabolic processes. Results: In the present study we reveal the molecular mechanism by which SGK 1 affects the phosphorylation of FOXO1 and FOXO3 thus regulating bovine fat deposition via the PI3K/Akt signaling pathway. SGK 1 was characterized primarily in the bovine kidney, where it peaked at day 6 of preadipocyte differentiation. Overexpression of SGK 1 in bovine preadipocytes promoted mRNA expression of adipose-specific genes, while cell cycle-related genes were repressed. Adipocyte differentiation-related proteins were not significantly changed, but proliferation-related proteins were markedly inhibited. Moreover, mRNA expression of adipose-specific genes were down-regulated while cell cycle-related genes were up-regulated in response to loss-of-function SGK 1. The expression of adipose differentiation-related proteins were significantly inhibited but proliferation-related proteins were not significantly changed. Overexpression of SGK 1 in bovine adipocytes significantly changed the gene expression enriched in the PI3K/Akt signaling pathways through RNA-seq. Subsequently, we found that overexpression of SGK 1 increased phosphorylation of FOXO1/FOXO3 and reduced protein expression, whereas SGK 1 deletion had opposite effects. Overall, we show that overexpression of SGK 1 promotes adipogenesis mainly via inhibiting preadipocyte proliferation, whereas the loss-of-function of SGK 1 represses adipogenesis mainly through inhibition of adipocyte differentiation. Mechanistically, SGK 1 changes the phosphorylation of two key genes located downstream in the PI3K/Akt signaling pathway, FOXO1/FOXO3, thus promoting fat deposition in cattle. Conclusion: These data reveal that SGK 1 is a positively regulatory during intramuscular adipogenesis of cattle, which expands the candidates regulating bovine adipogenesis and provides the security for human healthy from the aspect of high-quality beef.