The anti-adipogenic effect of macrophage-conditioned medium on on 3T3-L1 and human adipogenesis

Abstract

Macrophages accumulate in the adipose tissue of obese rodents and humans. We and others have reported that macrophage-secreted factors inhibit adipogenesis. This study aims to investigate the molecular mechanisms underlying this inhibitory effect. Murine 3T3-L1 preadipocytes were differentiated with medium conditioned by murine J774 macrophages (J774-MacCM) or human THP-1 macrophages (THP-1-MacCM). Clonal expansion, an early required adipogenic event, was inhibited by both MacCMs Rb phosphorylation, required for cell cycle progression, was impaired by J774-MacCM. To expand our studies to a more physiological setting, human abdominal subcutaneous preadipocytes were differentiated with THP-1-MacCM or with conditioned medium from blood monocyte-derived macrophages (MDM-CM) activated with LPS. The IKKbeta/NF-kappabeta pathway appeared to be required for the THP-1 MacCM anti-adipogenic effect. Furthermore, human preadipocytes differentiated in MDM-CM (LPS) displayed a distinct morphology, altered fibronectin expression, as well as reduced lipid accumulation and expression of adipogenic markers. These studies suggest that macrophage-secreted factors impair proximal events in the adipogenic program.