Adipocyte/macrophage fatty acid-binding proteins contribute to metabolic deterioration through actions in both macrophages and adipocytes in mice
Adipocyte/macrophage fatty acid-binding proteins contribute to metabolic deterioration through actions in both macrophages and adipocytes in mice
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DOI：
10.1172/jci34750
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发表时间：
2008-07-01
影响因子：
15.9
通讯作者：
Hotamisligil, Goekhan S.
中科院分区：
文献类型：
--
作者：
Furuhashi, Masato;Fucho, Raquel;Hotamisligil, Goekhan S.
脂肪组织炎症是肥胖的一个特征。然而，调节这种炎症反应的机制以及脂肪炎症与全身代谢后果之间的联系尚不完全清楚。在本研究中，我们利用脂肪细胞/巨噬细胞脂肪酸结合蛋白（FABPs） aP2 （FABP4）和mal1 （FABP5）的高度限制性共表达，研究了巨噬细胞和脂肪细胞中这些脂质伴侣对小鼠局部和全身炎症和代谢稳态的贡献。脂肪细胞中FABPs的缺失导致巨噬细胞中炎症细胞因子的表达减少，而巨噬细胞中相同的缺失导致脂肪细胞中胰岛素信号传导和葡萄糖摄取增强。通过骨髓移植放射嵌合，我们在体内培养了骨髓和基质源性元件FABP缺乏的小鼠，并研究了每种细胞靶点对饮食性肥胖的局部和全身胰岛素作用和葡萄糖代谢的影响。这些实验结果表明，无论是巨噬细胞还是脂肪细胞都不能单独解释FABPs对全身代谢的总影响，并表明这两种细胞类型之间的相互作用，特别是脂肪组织中的相互作用，对于代谢恶化的炎症基础至关重要。
Adipose tissue inflammation is a characteristic of obesity. However, the mechanisms that regulate this inflammatory response and link adipose inflammation to systemic metabolic consequences are not fully understood. In this study, we have taken advantage of the highly restricted coexpression of adipocyte/macrophage fatty acid-binding proteins (FABPs) aP2 (FABP4) and mal1 (FABP5) to examine the contribution of these lipid chaperones in macrophages and adipocytes to local and systemic inflammation and metabolic homeostasis in mice. Deletion of FABPs in adipocytes resulted in reduced expression of inflammatory cytokines in macrophages, whereas the same deletion in macrophages led to enhanced insulin signaling and glucose uptake in adipocytes. Using radiation chimerism through bone marrow transplantation, we generated mice with FABP deficiency in bone marrow and stroma-derived elements in vivo and studied the impact of each cellular target on local and systemic insulin action and glucose metabolism in dietary obesity. The results of these experiments indicated that neither macrophages nor adipocytes individually could account for the total impact of FABPs on systemic metabolism and suggest that interactions between these 2 cell types, particularly in adipose tissue, are critical for the inflammatory basis of metabolic deterioration.