Fatty acid-binding protein 5 regulates diet-induced obesity via GIP secretion from enteroendocrine K cells in response to fat ingestion
Fatty acid-binding protein 5 regulates diet-induced obesity via GIP secretion from enteroendocrine K cells in response to fat ingestion
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DOI：
10.1152/ajpendo.00543.2014
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发表时间：
2015-04-01
影响因子：
5.1
通讯作者：
Inagaki, Nobuya
中科院分区：
文献类型：
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作者：
Shibue, Kimitaka;Yamane, Shunsuke;Inagaki, Nobuya
胃抑制多肽（GIP）是肠内分泌K细胞在摄入营养物质，尤其是脂肪时释放的一种肠促胰岛素。GIP是导致肥胖的脂肪堆积的因素之一。最近的一项研究表明，脂肪酸结合蛋白5 （FABP5）在小鼠K细胞中表达，并参与脂肪诱导的GIP分泌。我们研究了脂肪诱导的GIP分泌机制以及fabp5相关的GIP反应对饮食性肥胖（DIO）的影响。单次口服葡萄糖和脂肪导致全身FABP5敲除（FABP5(-/-)）小鼠对脂肪而不是葡萄糖的GIP反应降低40%，K细胞计数和K细胞中GIP含量没有变化。在离体上小肠实验中，油酸仅诱导GIP释放轻微增加，在FABP5（-/-）样品中，胆汁和油酸联合施用可显著增强GIP释放，并减弱GIP反应。与野生型（FABP5(+/+)）小鼠相比，高脂饮食下FABP5（-/-）小鼠的体重增加和体脂量减少了24%；GIP- gfp纯合敲入(GIP(gfp/gfp))- fabp5（+/+）小鼠与GIP(gfp/gfp)- fabp5（-/-）小鼠之间无差异，GIP基因缺失。这些结果表明，胆汁有效地放大了脂肪诱导的GIP分泌，而FABP5以GIP依赖的方式促进了DIO的发展。
Gastric inhibitory polypeptide (GIP) is an incretin released from enteroendocrine K cells in response to nutrient intake, especially fat. GIP is one of the contributing factors inducing fat accumulation that results in obesity. A recent study shows that fatty acid-binding protein 5 (FABP5) is expressed in murine K cells and is involved in fat-induced GIP secretion. We investigated the mechanism of fat-induced GIP secretion and the impact of FABP5-related GIP response on diet-induced obesity (DIO). Single oral administration of glucose and fat resulted in a 40% reduction of GIP response to fat but not to glucose in whole body FABP5-knockout (FABP5(-/-)) mice, with no change in K cell count or GIP content in K cells. In an ex vivo experiment using isolated upper small intestine, oleic acid induced only a slight increase in GIP release, which was markedly enhanced by coadministration of bile and oleic acid together with attenuated GIP response in the FABP5(-/-) sample. FABP5(-/-) mice exhibited a 24% reduction in body weight gain and body fat mass under a high-fat diet compared with wild-type (FABP5(+/+)) mice; the difference was not observed between GIP-GFP homozygous knock-in (GIP(gfp/gfp))-FABP5(+/+) mice and GIP(gfp/gfp)-FABP5(-/-) mice, in which GIP is genetically deleted. These results demonstrate that bile efficiently amplifies fat-induced GIP secretion and that FABP5 contributes to the development of DIO in a GIP-dependent manner.