Medium-chain fatty acids activate fructose metabolism via up-regulating GLUT5-KHK axis

Fructose is an abundant monosaccharide in the human diet and an important source of energy in the human body. GLUT5, a member of facilitative glucose transporter family, is the only membrane transporter that specifically transports fructose in the human body, and plays an important role in dietary fructose uptake and metabolism. Previous studies have shown that medium-chain fatty acids (MCFAs) can regulate glucose metabolism via modulating glucose transporters. However, it has not been addressed if MCFAs can regulate GLUT5-mediated fructose metabolism. In the present study, we demonstrated for the first time that MCFAs but not short chain or long chain fatty acids are able to promote fructose uptake in both IEC-18 rat intestinal epithelial cells and human MDA-MB-231 breast cancer cells (a commonly used cell line for fructose metabolism-related study) measured by 1-NBD-Fructose-based assay, which are well correlated with the activation of GLUT5-KHK axis. Moreover, the activation of GLUT5-ketohexokinase (KHK) axis was also achieved in vivo by the treatment with tricapylin, a precursor of octanoic acid (OA), leading to the improvement in fructose-based energy recovery after fasting. The findings of the present study not only provide novel mechanistic support for MCFAs as regulator of carbohydrate metabolism, but also denote that MCFAs could be useable for managing fructose-associated metabolic diseases or as an enhancer for energy recovery after fasting or exercise.