Zhang Tingting, Wang Wei, Li Jiayu, Ye Xianlong, Wang Zhe, Cui Siyuan, Shen Shiwei, Liang Xinmiao, Chen Yong Q, Zhu Shenglong
Wuxi School of Medicine, Jiangnan University, Wuxi, China.
State Key Laboratory of Food Science and Resources, School of Food Science and Technology, Jiangnan University, Wuxi, China.
Nat Microbiol. 2025 Feb;10(2):348-361. doi: 10.1038/s41564-024-01902-8. Epub 2025 Jan 13.
Sugar preference is a key contributor to the overconsumption of sugar and the concomitant increase in the incidence of diabetes. However, the exact mechanism of its development remains ambiguous. Here we show that the expression of free fatty acid receptor Ffar4, a receptor for long-chain fatty acids, is decreased in patients and mouse models with diabetes, which is associated with high sugar intake. Deletion of intestinal Ffar4 in mice resulted in reduced gut Bacteroides vulgatus and its metabolite pantothenate, leading to dietary sugar preference. Pantothenate promoted the secretion of GLP-1 which inhibited sugar preference by stimulating hepatic FGF21 release, which in turn regulates energy metabolism. These findings uncover a previously unappreciated role of Ffar4 in negatively regulating sugar preference and suggest B. vulgatus-derived pantothenate as a potential therapeutic target for diabetes.
糖偏好是导致糖过度消费以及糖尿病发病率随之上升的关键因素。然而，其发展的确切机制仍不明确。在此我们表明，游离脂肪酸受体Ffar4（一种长链脂肪酸受体）在糖尿病患者和小鼠模型中的表达降低，这与高糖摄入有关。在小鼠中敲除肠道Ffar4会导致肠道普通拟杆菌及其代谢产物泛酸盐减少，从而导致对膳食糖的偏好。泛酸盐促进胰高血糖素样肽-1（GLP-1）的分泌，GLP-1通过刺激肝脏成纤维细胞生长因子21（FGF21）释放来抑制糖偏好，而FGF21反过来调节能量代谢。这些发现揭示了Ffar4在负向调节糖偏好方面此前未被认识到的作用，并表明普通拟杆菌衍生的泛酸盐是糖尿病的一个潜在治疗靶点。
