The food contaminant deoxynivalenol provokes metabolic impairments resulting in non-alcoholic fatty liver (NAFL) in mice

Abstract

The ribotoxin deoxynivalenol (DON) is a trichothecene found on cereals responsible for mycotoxicosis in both humans and farm animals. DON toxicity is characterized by reduced food intake, diminished nutritional efficiency and immunologic effects. The present study was designed to further characterize the alterations in energy metabolism induced by DON intoxication. We demonstrated that acute DON intoxication triggered liver steatosis associated with an altered expression of genes related to lipids oxidation, lipogenesis and lipolysis. This steatosis was concomitant to anorexia, hypoglycemia and a paradoxical transient insulin release. DON treatment resulted also in stimulation of central autonomic network regulating sympathetic outflow and adrenaline and glucocorticoids secretion. Furthermore, an increased expression of genes linked to inflammation and reticulum endoplasmic stress was observed in the liver of DON-treated mice. Finally, we propose that lipids mobilization from adipose tissues (AT) induced by DON intoxication drives hepatic steatosis since (1) genes encoding lipolytic enzymes were up-regulated in AT and (2) plasma concentration of triglycerides (TGs) and nonesterified fatty acids were increased during DON intoxication. Altogether, these data demonstrate that DON induced hormonal and metabolic dysregulations associated with a spectrum of hepatic abnormalities, evocative of a non-alcoholic fatty liver disease.

Orphan Nuclear Receptor RORγ Modulates the Genome-Wide Binding of the Cholesterol Metabolic Genes during Mycotoxin-Induced Liver Injury

“…In contrast, food contaminated with DON causes non-alcoholic fatty liver disease (NAFLD) in mice due to metabolic impairments. Notably in this study, the DON associated lipogenesis ( FASN and SCF1 ) and cholesterogenesis ( HMGCR ) pathways were first upregulated, but then followed by a down-regulation [ 44 ], implying a possible exhaustion and fat degeneration caused by mycotoxins. We have demonstrated that mycotoxin intoxication fundamentally alters the hepatic cholesterol biosynthesis gene program.…”

Global distribution, toxicity to humans and animals, biodegradation, and nutritional mitigation of deoxynivalenol: A review

“…The liver is the most vital metabolic and detoxification organ in human and animal bodies, and the majority of mycotoxins can damage the liver and cause hepatotoxicity (Mao et al., 2022). Recent studies have proven that DON induces liver injury in pigs, mice, and other animals, such as driving hepatic steatosis by lipid mobilization from adipose tissues induced by DON intoxication, causing liver fibrosis and inflammation (Figure 2) (Barbouche et al., 2020; Mao et al., 2022; Skiepko et al., 2020). And beyond that, DON can induce cellular oxidative stress, apoptosis, and autophagy, and the mechanism of hepatotoxicity is oxidative stress (Nrf2/HO‐1), which contributes to liver injury transcription factor activation, inflammation, and apoptosis (Figure 2) (Ruan et al., 2022).…”

Constitutively active microglial populations limit anorexia induced by the food contaminant deoxynivalenol

“…Immune cell lines have been shown to be highly sensitive to DON and respond by upregulating pro-inflammatory cytokine expression in vitro [ 18 , 26 ]. Several studies have shown an up-regulation of pro-inflammatory cytokines: interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) in peripheral organs such as the spleen, liver, kidney, and small intestine [ 27 , 28 ]. Interestingly, a direct link between DON-induced reduction in food intake and cytokines up-regulation after acute oral DON administration has been demonstrated [ 29 , 30 ].…”