Anorexic action of fusarenon-x in the hypothalamus and intestine. (November 2020)

• Record Type: Journal Article
• Authors: Tominaga, Misa; Ichikawa, Saori; Sakashita, Fumiko; Tadaishi, Miki; Shimizu, Makoto; Kobayashi-Hattori, Kazuo
• Is Part Of: Toxicon. Volume 187(2020)
• Page Start: 57
• Page End: 64
• Publication Date: 2020-11
• Subjects: Fusarenon-x -- Anorexia -- Hypothalamus -- Intestine -- Inflammatory cytokines -- Cholecystokinin; AGRP agouti-related peptide -- BDNF brain-derived neurotrophic factor -- CART cocaine- and amphetamine-regulated transcript -- CaSR calcium-sensing receptor -- CCK cholecystokinin -- CRH corticotrophin-releasing hormone -- DON deoxynivalenol -- FX fusarenon-x -- IκBα inhibitor kappa B alpha -- IKK IκB kinase -- IL-1β interleukin-1β -- IL-6 interleukin-6 -- MC4R melanocortin 4 receptor -- NF-κB nuclear factor-kappa B -- NPY neuropeptide Y -- PBS phosphate-buffered saline -- POMC pro-opiomelanocortin -- PVDF polyvinylidene fluoride -- PYY peptide YY -- TBST tris-buffered saline containing 0.05% (v/v) Tween 20 -- TNF-α tumor necrosis factor-α -- TrkB tyrosine kinase receptor B -- TRPA1 transient receptor potential ankyrin-1 -- TRPM5 transient receptor potential cation channel subfamily M member 5 -- SDS sodium dodecyl sulfate -- SE standard error; Toxins -- Periodicals; Venom -- Periodicals; 615.9
• DOI: 10.1016/j.toxicon.2020.08.028
• Languages: English
• ISSNs: 0041-0101

Abstract

Abstract: There is a lack of information available on the anorexic action of fusarenon-x (FX), which is a sesquiterpenoid mycotoxin. In this study, we investigated the changes in the hypothalamus and small intestine related to appetite after oral FX exposure. The time-course change of food intake after oral FX exposure (0.5, 1.0, and 2.5 mg/kg bw) in B6C3F1 mice showed that 2.5 mg/kg bw of FX significantly suppressed food intake during 3–6 h compared to the control. Furthermore, the total food intake for 24 h was lower in the group exposed to FX than in the control. The FX exposure (2.5 mg/kg bw for 3 h) significantly increased mRNA levels of anorexic hormones (pro-opiomelanocortin (POMC) and cocaine- and amphetamine-regulated transcription (CART)) without changing the mRNA levels of orexigenic hormones. In addition, FX exposure indicated significantly higher mRNA levels of possible downstream targets of anorexic POMC neurons, such as the melanocortin 4 receptor (MC4R), brain-derived neurotrophic factor (BDNF) and tyrosine kinase receptor B (TrkB), in the hypothalamus compared to the control. FX exposure also significantly increased the mRNA level of inflammatory cytokines (tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β)) and activated nuclear factor-kappa B (NF-κB), which is a regulatory factor for POMC in the hypothalamus. In the intestine, FX exposure did not affect the mRNA level of anorexic peptide YY but significantly elevated that of anorexic cholecystokinin (CCK) and regulatory factors for CCK (calcium-sensing receptor (CaSR), the transient receptor potential ankyrin-1 channel (TRPA1), and transient receptor potential cation channel subfamily M member 5 (TRPM5)). These results suggest that FX sequentially induces inflammatory cytokine expression, NF-κB activation, and POMC expression in the hypothalamus. FX also induces CCK expression in the intestine possibly via induction of CaSR, TRPM5, and TRPA1 expression. These changes will eventually lead to the anorexic action of FX. Highlights: Fusarenon-x elevated the hypothalamic mRNA level of pro-opiomelanocortin, an anorexic hormone and its downstream factors. Fusarenon-x increased the hypothalamic mRNA level of inflammatory cytokines and activated nuclear factor kappa B. The inflammatory responses caused by fusarenon-x induced anorexic hormones in the hypothalamus. Fusarenon-x increased the intestinal mRNA level of cholecystokinin, an anorexic hormone. The anorexic action of fusarenon-x results from the induction of the hypothalamic and intestinal anorexic hormones.