Key result
Macrophage-adipocyte coculture downregulated GLUT4 transcripts and inhibited Akt phosphorylation within 15 min of insulin stimulation, disrupting glucose transport and adipocyte differentiation.
Why the study?
Does the interaction between macrophages and adipocytes affect insulin resistance by disrupting insulin-stimulated glucose transport, adipocyte differentiation, and macrophage function?
Does the interaction between macrophages and adipocytes affect insulin resistance by disrupting insulin-stimulated glucose transport, adipocyte differentiation, and macrophage function?
Macrophage-adipocyte interactions disrupt insulin-stimulated glucose transport and adipocyte differentiation, primarily mediated by cytokines like IL-6, contributing to insulin resistance in obesity.
May implicate macrophage-adipocyte interactions in obesity-related insulin resistance; hypothesis-generating for human therapeutic targeting.
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 macrophage TNF-alpha, IL-6, or IL-1beta transcript concentrations relative to those obtained when C2D macrophages were incubated alone. However, preadipocytes and adipocytes increased PEC-C2D macrophage IL-6 transcript levels, while preadipocytes inhibited IL-1beta transcript 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-alpha), interleukin 1beta (IL-1beta), and, in some cases, IL-6. C2D macrophages increasingly downregulated GLUT4 transcript levels in differentiated adipocytes. Recombinant TNF-alpha, IL-1beta, and IL-6 also downregulated GLUT4 transcript levels relative to those for the control. However, only IL-6 was inhibitory at concentrations detected in macrophage-adipocyte cocultures. IL-6 and TNF-alpha, but not IL-1beta, 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-alpha, IL-6, and IL-1beta, 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.
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Xie et al. (2010) studied Obesity and insulin resistance. Macrophage-adipocyte coculture vs. Cells incubated alone was evaluated on Insulin-stimulated glucose transport, adipocyte differentiation, and macrophage function. Macrophage-adipocyte coculture downregulated GLUT4 transcripts and inhibited Akt phosphorylation within 15 min of insulin stimulation, disrupting glucose transport and adipocyte differentiation.
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