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Session: Advances in Experimental Animal Nutrition (Oral 17)

(OR17-04-24) Targeting Intestinal Transporter Glut5 to Prevent the High Fructose-Induced Steatotic Liver Disease

Sunday, June 30, 2024
4:36 PM – 4:48 PM CT
Location:  W183

    Presenting Author(s)

  • Yan Ni, PhD (she/her/hers)

    Professor
    Children’s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health
    Hangzhou, Zhejiang, China (People's Republic)

    Disclosure(s): No relevant financial relationship(s) with ineligible companies to disclose.

    • Co-Author(s)

  • HW

    Huiying Wang

    Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, China (People's Republic)

Objectives: Over consumption of dietary fructose contributes to the development of metabolic dysfunction associated-steatotic liver disease (MASLD), but the role of fructose transporter in the intestine, glucose transporter 5 (GLUT5), is not clear. We aimed to investigate the role of GLUT5 as a novel therapeutic target for MASLD.

Methods: Adult male C57BL/6J mice were fed by different doses of fructose in drinking water for 8 weeks from 4%-25%. The intestinal expression of GLUT5, intestinal and liver histology were measured while gut metagenome and metabolome were evaluated. The intestinal-specific Glut5 knock out mice Glut5flox/flox Vil1-Cre ki/wt (Glut5-/-) were built and fed by high fructose alone (HF) or combined with high fat diet (HFF) for 8 weeks to confirm the role of Glut5. Furthermore, we fed 5,6,7-Trimethoxyflavone (TMF), a natural product identified as GLUT5 transporter inhibitor, to wide type (WT) mice to validate its prevention effect on high fructose-induced liver injury.

Results: The intestinal GLUT5 expression was significantly increased in WT mice fed by HF for 8 weeks, which developed gut dysbiosis, impaired liver function, and metabolic abnormalities. Compared with WT mice, after feeding HF or HFF diet for 8 weeks, the intestinal and liver damage were alleviated in Glut5-/- mice. Moreover, we confirmed that the natural product, TMF, could effectively inhibited the intestinal expression of GLUT5 and improved the development of MASLD in WT mice.

Conclusions: The intestinal GLUT5 is a potential therapeutic target to alleviate the high fructose-induced MASLD and the natural product of GLUT5 inhibitor-TMF can be a promising candidate for MASLD prevention and intervention.

Funding Sources: This work was funded by the National Natural Science Foundation of China (82170583, 81900510).