Fatty acid binding protein 4 and 5 play a crucial role in thermogenesis under the conditions of fasting and cold stress.
Fatty acid binding protein 4 and 5 play a crucial role in thermogenesis under the conditions of fasting and cold stress.
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DOI：
10.1371/journal.pone.0090825
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Kurabayashi M
中科院分区：
文献类型：
--
作者：
Syamsunarno MR;Iso T;Yamaguchi A;Hanaoka H;Putri M;Obokata M;Sunaga H;Koitabashi N;Matsui H;Maeda K;Endo K;Tsushima Y;Yokoyama T;Kurabayashi M
当体温调节机制（包括脂肪酸 (FA) 的利用）受到干扰时，在寒冷环境下会迅速诱发体温过低。 FA结合蛋白4（FABP4）和FABP5在脂肪组织和巨噬细胞中大量表达，已被确定为营养过剩相关疾病（例如胰岛素抵抗和动脉粥样硬化）发病机制中的关键分子。我们最近发现 FABP4/5 在心脏和骨骼肌的毛细血管内皮细胞中显着表达，并在这些组织中的 FA 利用中发挥着至关重要的作用。然而，FABP4/5 在生热作用中的作用仍有待确定。在这项研究中，我们发现缺乏 FABP4 和 FABP5 的小鼠（DKO 小鼠）生热作用严重受损，这在禁食期间暴露于冷环境后不久就表现出来。在 DKO 小鼠中，禁食后，棕色脂肪组织 (BAT) 中的三酰甘油和骨骼肌 (SkM) 中的糖原储存几乎耗尽，使用 125I-BMIPP 进行的生物分布分析表明，尽管血清 NEFA 水平大幅升高，但非酯化 FA (NEFA) 并未被 BAT 有效吸收。除了在禁食期间在 DKO 小鼠中观察到的严重低血糖之外，冷暴露并没有诱导 BAT 摄取葡萄糖类似物 18F-FDG。这些发现强烈表明，由于 BAT 和 SkM 中能量储存的耗尽以及这些组织的能量底物供应减少，DKO 小鼠在禁食后表现出明显的体温过低。总之，FABP4/5 在 BAT 和 SkM 的产热过程中发挥着不可或缺的作用。我们的研究强调了 FABP4/5 对于克服危及生命的环境（例如寒冷和饥饿）的重要性。
Hypothermia is rapidly induced during cold exposure when thermoregulatory mechanisms, including fatty acid (FA) utilization, are disturbed. FA binding protein 4 (FABP4) and FABP5, which are abundantly expressed in adipose tissues and macrophages, have been identified as key molecules in the pathogenesis of overnutrition-related diseases, such as insulin resistance and atherosclerosis. We have recently shown that FABP4/5 are prominently expressed in capillary endothelial cells in the heart and skeletal muscle and play a crucial role in FA utilization in these tissues. However, the role of FABP4/5 in thermogenesis remains to be determined. In this study, we showed that thermogenesis is severely impaired in mice lacking both FABP4 and FABP5 (DKO mice), as manifested shortly after cold exposure during fasting. In DKO mice, the storage of both triacylglycerol in brown adipose tissue (BAT) and glycogen in skeletal muscle (SkM) was nearly depleted after fasting, and a biodistribution analysis using 125I-BMIPP revealed that non-esterified FAs (NEFAs) are not efficiently taken up by BAT despite the robustly elevated levels of serum NEFAs. In addition to the severe hypoglycemia observed in DKO mice during fasting, cold exposure did not induce the uptake of glucose analogue 18F-FDG by BAT. These findings strongly suggest that DKO mice exhibit pronounced hypothermia after fasting due to the depletion of energy storage in BAT and SkM and the reduced supply of energy substrates to these tissues. In conclusion, FABP4/5 play an indispensable role in thermogenesis in BAT and SkM. Our study underscores the importance of FABP4/5 for overcoming life-threatening environments, such as cold and starvation.
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