2. Academic Validation
  3. Deoxynivalenol-induced anorexia is mediated by brain-gut peptides through CaSR-TRPM5 signaling axis

Deoxynivalenol-induced anorexia is mediated by brain-gut peptides through CaSR-TRPM5 signaling axis

  • Toxicon. 2026 Jan:269:108660. doi: 10.1016/j.toxicon.2025.108660.
Xiaojie Meng 1,  Jianming Yue 2,  Zihui Qin 2,  Huiping Xiao 1,  Xia Tang 1,  Wenda Wu 3
Affiliations

Affiliations

  • 1 MOE Engineering Research Center of Bio-process, Key Laboratory for Animal Food Green Manufacturing and Resource Mining of Anhui Province, School of Food and Biological Engineering, Hefei University of Technology, Hefei, 230009, China.
  • 2 MOE Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, 210095, China.
  • 3 MOE Engineering Research Center of Bio-process, Key Laboratory for Animal Food Green Manufacturing and Resource Mining of Anhui Province, School of Food and Biological Engineering, Hefei University of Technology, Hefei, 230009, China; Xinjiang Key Laboratory of Grassland Resources and Ecology, College of Grassland Science, Xinjiang Agricultural University, Urumgi, 830052, China; Department of Chemistry, Faculty of Science, University of Hradec Kralove, Hradec Kralove, 50003, Czech Republic. Electronic address: [email protected].
PMID: 41241198 DOI: 10.1016/j.toxicon.2025.108660
Abstract

Deoxynivalenol (DON), a secondary metabolite produced by Fusarium, can widely contaminate foods and feeds, endangering human and animal health. DON can cause anorexia in Animals. However, the specific mechanism is unclear. In this study, in vivo and in vitro experiments were conducted in mice and mouse intestinal Organoid, respectively. Specific antagonists NPS2143, U73122, Xestospongin C, TPPO, EGTA, and Nitrendipine were selected to inhibit CaSR, PLCβ2, IP3R, TRPM5, extracellular calcium, and L-type VSCCs to explore the effect of the CaSR-TRPM5 signaling axis in DON-induced anorexia and secretion of brain-gut peptide. The results showed that these antagonists attenuated the DON-induced anorexia and secretion of the brain-gut peptides CCK, PYY, GLP-1, and GIP. DON could significantly increase the expression of hypothalamic anorectic genes MC4R, POMC, and CART. Blocking the CaSR-TRPM5 signaling axis could attenuate these changes. The mouse small intestinal Organoid can be induced to differentiate into EECs by blocking the Wnt/Notch/MEK pathway. DON-induced brain-gut peptides secretion was attenuated by inhibition of CaSR-TRPM5 signaling axis in mouse intestinal Organoid. In summary, DON could act on enteroendocrine cells to induce secretion of brain-gut peptide and activate the hypothalamic anorectic genes to evoke anorexia through the CaSR-TRPM5 signaling axis.

Keywords

Anorexia; Brain-gut peptide; CaSR-TRPM5 axis; Deoxynivalenol; Intestinal organoid.

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