52 | EFFECTS OF DIETARY FRUCTOSE ON DUODENAL MUCIN GLYCOSYLATION AND MUCUS PRODUCTION IN MICE FED A HIGH-FAT DIET

D. Mentino¹, A. Provera², C. Vecchio², A. Antonioli², A.N. Sheferaw², N. Taldone¹, R. Vitale³, C. Passamonti⁴, S. Fensore⁵, F. Prodam², S. Sutti², M. Mastrodonato^1|6, M. F. Faienza³ | ¹Department of Biosciences, Biotechnology and Environment, University of Bari Aldo Moro, Italy; ²Department of Health Sciences, University of Piemonte Orientale, Novara, Italy; ³ Department of Mathematics, University of Luxembourg, Belval Esch-sur-Alzette, Luxembourg; ⁴Department of Socio-Economic, Managerial and Statistical Studies, University of Chieti-Pescara, 3Pediatric Unit, Department of Precision and Regenerative Medicine and Ionian Area, University of Bari Aldo Moro, Italy; ⁶National Research Council of Italy (CNR) - Water Research Institute (IRSA),Taranto, Italy

Dietary fructose is associated with obesity1 and metabolic alterations, yet its effects on intestinal mucins and mucus glycosylation remain poorly understood. This study investigated whether fructose supplementation modulates high-fat diet (HFD)-induced changes in duodenal mucin production in an age-dependent manner. Young and adult mice were fed a normal diet (ND), HFD, or HFD supplemented with 30% fructose in drinking water (HFD+Fru) for 16 weeks. Brunner’s glands and villus goblet cells were analyzed by conventional histochemistry and a panel of lectins to evaluate possible alterations in intestinal mucus glycosylation. Results showed that both HFD and HFD+Fru significantly increased body weight. In young mice, HFD+Fru induced a compensatory mucosal response characterized by increased PAS reactivity, enhanced sialylated mucin secretion, and higher SNA and PNA reactivity in villus goblet cells. In contrast, adult mice showed a maladaptive phenotype, with reduced PAS-positive mucins, decreased mucin secretion, diminished sialylation and GlcNAc expression, and marked loss of fucosylation in Brunner’s glands and villus goblet cells. These findings demonstrate that fructose-enriched HFD remodels duodenal mucin O-glycosylation in an age-dependent manner, promoting adaptive responses in young mice but impaired epithelial barrier protection in adults. Such alterations may contribute to diet-related intestinal dysfunction and obesity-associated complications later in life.
Acknowledgments: This study was supported by the Cariplo Foundation (prot. 2021-4652) project NODES, which has received funding from the MUR—M4C2 1.5 of PNRR with grant agreement no. ECS00000036.