Exogenous Sodium Pyruvate Stimulates Adipogenesis of 3T3‐L1 Cells

Abstract

We investigated the effects of exogenous sodium pyruvate (SP) on adipocyte differentiation, lipid accumulation, and the mRNA expression levels of adipogenesis-related genes in 3T3-L1 pre-adipocytes. Differentiation of pre-adipocytes was induced by MDI (3-isobutyl-1-methylxanthine: IBMX, dexamethasone: DEX, and insulin), in the presence or absence of SP. Adipogenesis was stimulated by SP in a concentration-dependent manner. SP also induced the expression of genes encoding aP2, GLUT4, and adiponectin, but had no effect on cell proliferation. Exogenous glucose did not promote adipogenesis or lipid accumulation. 2-deoxy-D-glucose inhibited adipogenesis initiated by MDI, but failed to influence the effects of SP on adipogenesis, whereas 3-bromopyruvate inhibited adipogenesis regardless of whether SP was present. The pro-adipogenic properties of SP were limited to the early events of adipogenesis. To determine whether SP mimics the adipogenic action of dexamethasone or insulin, we examined the effects of SP on adipogenesis with combinations of IBMX, DEX, and insulin. SP did not improve incomplete lipid accumulation observed in cells grown under IBMX-, DEX-, or insulin-free conditions. Insulin-stimulated ERK1/2 phosphorylation was diminished by SP, while phosphorylation of Akt was increased, correlating with increased glucose uptake in response to insulin. We also observed that SP stimulated immediate early expression of C/EBPβ and C/EBPδ. The PPARγ antagonist GW9662 inhibited adipogenesis. Our findings highlight the adipogenic function of exogenous SP by stimulating early events of adipogenesis.

Non-ammoniagenic proliferation and differentiation media for cultivated adipose tissue

“…The effect of Pyr has previously been described in a study using fibroblasts, where it prevented mitochondrial dysfunction and senescence ( Kim et al, 2018 ). Another study reported, in alignment with our findings, that Pyr increased lipid droplet formation in adipocyte-like 3T3-L1 cells ( Hwang et al, 2016 ).…”

Near-Physiological Concentrations of Extracellular Pyruvate Stimulated Glucose Utilization along with Triglyceride Accumulation and Mitochondrial Activity in HepG2 Cells

“…The differentiated cells accumulated lipids and exhibited increased glucose uptake in response to pyruvate in the presence of insulin (17). Unlike the previous reports by others (15)(16)(17), this paper revealed that pyruvate stimulated glucose uptake at 0.1 mM, the concentration almost equal to the upper physiological limit in plasma (8, 9) (Fig. 3).…”

“…On the other hand, 5 mM pyruvate prevented palmitate-induced impairment of glucose uptake in C2 myotubes (16), although that report did not examine the effects of pyruvate without palmitate treatment. In another study using 3T3-L1 pre-adipocytes, exposure to 25 mM pyruvate promoted adipogenesis only in the presence of an induction mixture (17). The differentiated cells accumulated lipids and exhibited increased glucose uptake in response to pyruvate in the presence of insulin (17).…”

“…In another study, concomitant exposure to 25 mM pyruvate and an adipogenic cocktail (0.5 mM 3-isobutyl-1-methylxanthine, 1 mM dexamethasone and 1 mg/ mL insulin) induced 3T3-L1 preadipocytes to undergo adipogenic differentiation. This resulted in increase in insulin-stimulated glucose uptake, glucose transporter 4 mRNA expression, and intracellular triglyceride (TG) levels (17). These reports suggest that pyruvate may regulate glucose metabolism.…”