Interactive Changes between Macrophages and Adipocytes

Obesity is associated with a proinflammatory state, with macrophage infiltration into adipose tissue. We tested the hypothesis that communication between macrophages and adipocytes affects insulin resistance by disrupting insulin-stimulated glucose transport, adipocyte differentiation, and macrophage function. To test this hypothesis, we cocultured 3T3-L1 adipocytes with C2D macrophages or primary peritoneal mouse macrophages and examined the impacts of macrophages and adipocytes on each other. Adipocytes and preadipocytes did not affect C2D macrophageTNF-α,IL-6, orIL-1βtranscript concentrations relative to those obtained when C2D macrophages were incubated alone. However, preadipocytes and adipocytes increased PEC-C2D macrophageIL-6transcript levels, while preadipocytes inhibitedIL-1βtranscript levels compared to those obtained when PEC-C2D macrophages were incubated in medium alone. We found that adipocyte coculture increased macrophage consumption of tumor necrosis factor alpha (TNF-α), interleukin 1β (IL-1β), and, in some cases, IL-6. C2D macrophages increasingly downregulatedGLUT4transcript levels in differentiated adipocytes. Recombinant TNF-α, IL-1β, and IL-6 also downregulatedGLUT4transcript levels relative to those for the control. However, only IL-6 was inhibitory at concentrations detected in macrophage-adipocyte cocultures. IL-6 and TNF-α, but not IL-1β, inhibited Akt phosphorylation within 15 min of insulin stimulation, but only IL-6 was inhibitory 30 min after stimulation. Lastly, we found that adipocyte differentiation was inhibited by macrophages or by recombinant TNF-α, IL-6, and IL-1β, with IL-6 having the most impact. These data suggest that the interaction between macrophages and adipocytes is a complex process, and they support the hypothesis that the macrophage-adipocyte interaction affects insulin resistance by disrupting insulin-stimulated glucose transport, adipocyte differentiation, and macrophage function.