fumonisin-b1 and Obesity

Neural tube defects (NTDs) are serious malformations affecting approximately 1 per 1000 births, yet the mechanisms by which they arise are unknown. There have been consistent efforts in many fields of research to elucidate the etiology of this multifactorial condition. While no single gene has been identified as a major independent risk factor for NTDs, candidate genes have been proposed that may modify the effects of maternal and/or embryonic exposures. Folate supplementation effectively reduces the occurrence of NTDs and, consequently, has focused much research on metabolism of folate-related pathways during pregnancy and development. Further understanding of normal development and how teratogens can perturb these orchestrated processes also remains at the fore of modern scientific endeavors. The composite of these factors remains fragmented; the aim of this review is to provide the reader with a summary of sentinel and current works in the body of literature addressing NTD disease etiology.

Topics: Central Nervous System; Diabetes Complications; Drug-Related Side Effects and Adverse Reactions; Female; Fever; Folic Acid; Fumonisins; Humans; Neural Tube Defects; Obesity; Pregnancy; Risk Factors; Teratogens; Vitamin B 12

Obesity, which is a worldwide public health issue, is associated with chronic inflammation that contribute to long-term complications, including insulin resistance, type 2 diabetes and non-alcoholic fatty liver disease. We hypothesized that obesity may also influence the sensitivity to food contaminants, such as fumonisin B1 (FB1), a mycotoxin produced mainly by the Fusarium verticillioides. FB1, a common contaminant of corn, is the most abundant and best characterized member of the fumonisins family. We investigated whether diet-induced obesity could modulate the sensitivity to oral FB1 exposure, with emphasis on gut health and hepatotoxicity. Thus, metabolic effects of FB1 were assessed in obese and non-obese male C57BL/6J mice. Mice received a high-fat diet (HFD) or normal chow diet (CHOW) for 15 weeks. Then, during the last three weeks, mice were exposed to these diets in combination or not with FB1 (10 mg/kg body weight/day) through drinking water. As expected, HFD feeding induced significant body weight gain, increased fasting glycemia, and hepatic steatosis. Combined exposure to HFD and FB1 resulted in body weight loss and a decrease in fasting blood glucose level. This co-exposition also induces gut dysbiosis, an increase in plasma FB1 level, a decrease in liver weight and hepatic steatosis. Moreover, plasma transaminase levels were significantly increased and associated with liver inflammation in HFD/FB1-treated mice. Liver gene expression analysis revealed that the combined exposure to HFD and FB1 was associated with reduced expression of genes involved in lipogenesis and increased expression of immune response and cell cycle-associated genes. These results suggest that, in the context of obesity, FB1 exposure promotes gut dysbiosis and severe liver inflammation. To our knowledge, this study provides the first example of obesity-induced hepatitis in response to a food contaminant.

Topics: Animals; Chemical and Drug Induced Liver Injury; Diabetes Mellitus, Type 2; Dysbiosis; Fumonisins; Inflammation; Liver; Male; Mice; Mice, Inbred C57BL; Obesity