Src family kinases involved in the differentiation of human preadipocytes

Abstract

Background: Obesity is characterized by the excess accumulation of white adipose tissue (WAT). Src family kinases (SFKs) are non-receptor tyrosine kinases consisting of eight members (SRC, FYN, YES1, HCK, LCK, LYN, FGR and BLK) that have been studied extensively in mammalian cells. Although individual members in murine cells provide some clues that are associated with the regulation of adipogenesis, the specific role of this family in adipocyte differentiation has rarely been assessed, especially in human adipocytes.

Methods: Herein, we first explored the expression profiles of SFKs during human preadipocyte differentiation. Then, we used the pyrazolo-pyrimidinyl-amine compound PP1, a potent SFK inhibitor, to evaluate the function of SFKs during adipocyte differentiation. Furthermore, we adopted a loss-of-function strategy with siRNAs to determine the role of FGR in adipocyte differentiation.

Results: Here, we found that SRC, FYN, YES1, LYN and FGR were expressed in human preadipocytes and induced after the initiation of differentiation. Furthermore, the SFK inhibitor PP1 suppressed adipocyte differentiation. We also found that PP1 significantly suppressed the SFK activity in preadipocytes and decreased the expression of adipogenic genes in early and late differentiation. Given that FGR exhibited the most expression enhancement in mature adipocytes, we focused on FGR and found that its knockdown reduced lipid accumulation and adipogenic gene expression.

Conclusions: Collectively, these findings suggest that SFKs, especially FGR, are involved in the differentiation of human preadipocytes. Our results lay a foundation for further understanding the role of SFKs in adipocyte differentiation and provide new clues for anti-obesity therapies.

Keywords: Adipocyte differentiation; FGR; Obesity; PP1; SFKs.