SIRT1 inhibits adipogenesis and promotes myogenic differentiation in C3H10T1/2 pluripotent cells by regulating Wnt signaling

Abstract

BackgroundThe directed differentiation of mesenchymal stem cells (MSCs) is tightly controlled by a complex network. Wnt signaling pathways have an important function in controlling the fate of MSCs. However, the mechanism through which Wnt/β-catenin signaling is regulated in differentiation of MSCs remains unknown. SIRT1 plays an important role in the regulation of MSCs differentiation.ResultsThis study aimed to determine the effect of sirtuin 1 (SIRT1) on adipogenesis and myogenic differentiation of C3H10T1/2 cells. First, the MSC commitment and differentiation model was established by using 5-azacytidine. Using the established model, C3H10T1/2 cells were treated with SIRT1 activator/inhibitor during differentiation. The results showed that resveratrol inhibits adipogenic differentiation and improves myogenic differentiation, whereas nicotinamide promotes adipogenic differentiation. Notably, during commitment, resveratrol blocked adipocyte formation and promoted myotubes differentiation, whereas nicotinamide enhanced adipogenic potential of C3H10T1/2 cells. Furthermore, resveratrol elevated the expression of Cyclin D1 and β-catenin in the early stages. The luciferase assay showed that knockdown SIRT1 inhibits Wnt/β-catenin signaling, while resveratrol treatment or overexpression SIRT1 activates Wnt/β-catenin signaling. SIRT1 suppressed the expression of Wnt signaling antagonists sFRP2 and DACT1. Knockdown SIRT1 promoted adipogenic potential of C3H10T1/2 cells, whereas overexpression SIRT1 inhibited adipogenic differentiation and promoted myogenic differentiation.ConclusionsTogether, our results suggested that SIRT1 inhibits adipogenesis and stimulates myogenic differentiation by activating Wnt signaling.

Circular RNA hsa_circ_0076248 promotes oncogenesis of glioma by sponging miR‐181a to modulate SIRT1 expression

“…28 Conversely, Chen et al 50 indicated that miR-181a sensitized human malignant glioma cells to radiation; however, the role of miR-181a in human glioma chemoresistance, and more importantly, the downstream target and regulation mechanism that miR-181a regulated human glioma tumorigenesis, still needed more exploration. 33,34 Our sample analysis identified that the expression of miR-181a was lower in tumors than nontumor tissues. 30,35,37,42 These effects have been linked to cell behaviors, involving cell growth, differentiation, migration, and survival.…”

SIRT1 suppresses adipogenesis by activating Wnt/β-catenin signaling in vivo and in vitro

“…SIRT1 is knocked down by antisense oligonucleotides; consequently, the SIRT1 expression in MSCs is downregulated, and this finding demonstrates that SIRT1 can functionally inhibit osteogenesis and induce adipogenesis [24]. Our previous study found that resveratrol blocks adipocyte formation and promotes myotube differentiation in the established MSC commitment and differentiation model based on 5-azacytidine, which is a DNA methylation inhibitor [15]. By contrast, nicotinamide enhances the adipogenic potential of C3H10T1/2 cells [15].…”

“…Our previous study found that resveratrol blocks adipocyte formation and promotes myotube differentiation in the established MSC commitment and differentiation model based on 5-azacytidine, which is a DNA methylation inhibitor [15]. By contrast, nicotinamide enhances the adipogenic potential of C3H10T1/2 cells [15]. These studies implied that SIRT1-induced adipogenic suppression occurs throughout the whole process, particularly in the terminal differentiation of adipocyte and commitment differentiation of MSCs to a pre-adipocyte fate.…”

“…Compared with cells infected with the pLKO.1- SIRT1 vector, the stable cells downregulated the levels of SIRT1 and Wnt signaling antagonists that blocked adipogenesis (Figure 4) and thus improved the activity Wnt signaling to some degree. SIRT1 inhibits MSC commitment and differentiation to adipocytes by increasing Wnt signaling antagonist expression and activating the Wnt signaling pathway [15]. Nevertheless, the molecular mechanisms underlying SIRT1-inhibited adipogenesis should be further investigated.…”

“…For instance, SIRT1 activation inhibits adipocyte development and enhances the expression of osteoblast markers; by contrast, SIRT1 inhibition increases the number of adipocytes and promotes the expression of adipocyte markers in C3H10T1/2 [14]. SIRT1 is activated by resveratrol to inhibit adipogenic differentiation and improve myogenic differentiation; conversely, SIRT1 is inhibited by nicotinamide-promoted adipogenic differentiation [15]. In MSC-specific SIRT1-knocked out mice, the weight of subcutaneous fat decrease with small adipocytes and the concentration of blood triglycerides increase [16].…”