Macrophage-conditioned medium inhibits adipocyte differentiation

Abstract

Obesity is accompanied by a reduced adipogenic capacity that promotes a dipocyte hypertrophy, low-grade inflammation, and insulin resistance. Macrophages infiltrate adipose tissue and may contribute to the low-grade inflammation associated with obesity and insulin resistance, suggesting that they could also play an anti-adipogenic role. I hypothesized that macrophage-secreted factors inhibit adipogenesis. My objectives were to assess if macrophage-conditioned medium (MacCM) inhibits adipocyte differentiation and to determine the mechanism by which the inhibition occurs. Murine J774 or human THP-1 MacCM was added to murine 3T3-L1 or human abdominal subcutaneous or omental preadipocytes. Either type of MacCM impaired murine and human adipogenesis as measured by triglyceride accumulation and protein expression of adipogenic markers. Time course studies revealed that THP-1-MacCM was required during the early phase of 3T3-L1 adipogenesis for its inhibitory effect. THP-1-MacCM stimulated the phosphorylation of ERK1/2 and IKKbeta in 3T3-L1 preadipocytes. Pharmacological inhibition of ERK1/2, with the specific MEK1 inhibitor PD98059, alleviated the inhibitory effect of THP-1-MacCM on TG accumulation. In conclusion, MacCM inhibits adipocyte differentiation in culture. The antiadipogenic effect depends on early exposure of THP-1-MacM to differentiating 3T3-L1 preadipocytes, and ERK1/2 is required for the inhibitory effect of THP-1-MacCM on TG accumulation.