Editors' ChoiceObesity

Taking AIM at Adipocytes

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Science Signaling  15 Jun 2010:
Vol. 3, Issue 126, pp. ec179
DOI: 10.1126/scisignal.3126ec179

The adipose tissue of obese animals is under a state of prolonged inflammation, which is thought to be induced by infiltrating macrophages. This inflammatory state is associated with insulin resistance of adipose tissue, but whether macrophages influence adipocytes independently of their proinflammatory effects is unknown. Kurokawa et al. investigated the effects of the protein AIM (apoptosis inhibitor of macrophage), which this group previously showed is found in macrophages at atherosclerotic lesions; AIM can be secreted, but its functions are unclear. The authors showed that more macrophages infiltrated the adipose tissue of mice fed a high-fat diet (HFD) than accumulated in the adipose tissue of lean mice, and these macrophages were proinflammatory and secreted AIM into the surrounding tissue. Adipocytes, which did not express AIM, endocytosed AIM through the cell-surface scavenger receptor, CD36. Incubation of cultured adipocytes with recombinant AIM protein (rAIM) reduced the size of lipid droplets and increased the efflux of free fatty acids compared with those of untreated cells. Adipocytes in AIM–/– mice were larger than those in wild-type (WT) mice, and AIM–/– mice fed a HFD exhibited an accelerated increase in adipose tissue mass compared to that of WT mice. This increase in adipose tissue mass was inhibited by injection of AIM–/– mice with rAIM. When internalized into adipocytes, AIM interacted with fatty acid synthase (FAS) in a manner that inhibited its ability to synthesize saturated fatty acids. Thus, the authors speculate that the purpose of macrophage-derived AIM might be to decrease the progression of obesity by limiting the increase in adipose tissue mass.

J. Kurokawa, S. Arai, K. Nakashima, H. Nagano, A. Nishijima, K. Miyata, R. Ose, M. Mori, N. Kubota, T. Kadowaki, Y. Oike, H. Koga, M. Febbraio, T. Iwanaga, T. Miyazaki, Macrophage-derived AIM is endocytosed into adipocytes and decreases lipid droplets via inhibition of fatty acid synthase activity. Cell Metab. 11, 479–492 (2010). [PubMed]

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