SGK1 affects bovine adipocyte proliferation and differentiation via  regulation of the PI3K/Akt signaling pathway

Abstract

Objectives: Serum/glucocorticoid-inducible kinase 1 (SGK1) gene encodes a serine/threonine protein kinase that plays an essential role in cellular stress response and regulation of multiple metabolic processes. However, its role in bovine adipogenesis remains unknown. In this study, we aimed to clarify the role of SGK1 on bovine preadipocyte differentiation. Materials and Methods: Preadipocytes were induced to differentiation to detect the temporal expression pattern of SGK1. Heart, liver, lung, spleen, kidney, muscle and fat tissues were collected to detect its tissue expression profile. Recombinant adenovirus and the lentivirus were packaged for overexpression and knockdown. Oil Red O staining, quantitative real-time PCR, Western blot analysis, Yeast two-hybrid assay, and RNA-seq were performed to study the regulatory mechanism of SGK1. Results: SGK1 showed significantly higher expression in adipose and revealed significantly induced expression in differentiated adipocytes. Furthermore, overexpression of SGK1 greatly promoted adipogenesis and inhibited proliferation, which could be shown by the remarkable increasement of lipid droplet, and the expression levels of adipogenic marker genes and cell cycle-related genes. Inversely, its knockdown inhibited adipogenesis and facilitated proliferation. Mechanistically, SGK1 regulates the phosphorylation and expression of two critical genes located in the downstream of PI3K/Akt signaling pathway, FOXO1/FOXO3, thus promoting adipogenesis and inhibiting proliferation in cattle. Conclusions: SGK1 is required for bovinepreadipocyte proliferation and differentiation, which contributes to a better understanding of fat deposition in cattle.