AIMing at metabolic syndrome: towards development of novel therapies for modern metabolic diseases via macrophage-derived AIM
Metabolic syndrome is a cascade of metabolic diseases starting with obesity and progressing to atherosclerosis and is often fatal because of serious cardiovascular problems such as heart/brain infarction and hemorrhage. Accumulating evidence has revealed a critical involvement of inflammatory responses triggered by lesional macrophages in its pathogenesis. Importantly, we found that macrophages are associated with the progression of these diseases not only in the induction of inflammation but also in the production of apoptosis inhibitor of macrophage (AIM), which we initially identified as a soluble factor expressed by macrophages1. At atherosclerotic plaques, AIM is highly expressed by foam macrophages and inhibits apoptosis of these cells. This results in the accumulation of macrophages, causing inflammatory responses within the lesion, and ultimately disease progression2. In adipose tissue, macrophage-derived AIM is incorporated into adipocytes through CD36-mediated endocytosis, thereby reducing the activity of cytosolic fatty acid synthase. This unique response stimulates lipolysis, resulting in a decrease in adipocyte size, which is physiologically relevant to the prevention of obesity3. The lipolytic response also stimulates inflammation of adipocytes in association with the induction of metabolic disorders subsequent to obesity4. Thus, AIM is involved in the progression of metabolic syndrome in both advancing and inhibitory fashions. Regulation of AIM could therefore be therapeutically applicable for metabolic syndrome.
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2. Arai S et al. Cell Metab. 1 201, 2005.
3. Kurokawa J et al. Cell Metab. 11 479, 2010.
4. Kurokawa J et al. PNAS 108 12072, 2011.
Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.
Funding: This work was supported, however funding details are unavailable.