GSE202602
Arsenic exposure induces enterocyte lipid accumulation, resulting in the accelerated tissue growth and maturation during the suckling period
People with early life exposure to inorganic arsenic (iAs) have been associated with adverse health outcomes manifesting during both adolescence and adulthood, but the underlying mechanism is not fully understood. We found that acute oral iAs treatment to neonatal mice induces rapid accumulation of dietary fat in enterocytes, accelerating intestinal growth and enterocyte maturation. As gene regulation study underlines dysregulated lipid absorption pathways and apolipoprotein gene expressions, plasma lipoprotein abnormalities and atherogenic dyslipidemia were identified, highlighted by hypertriglyceridemia, and decreased HDL cholesterol. This pathological condition aggravates to early stages of NAFLD. In loss-of-function genetic models, these pathophysiological alterations induced by acute oral iAs exposure illustrates critical metabolic networks entailing LXR- and ATF4- regulatory schemes. Our findings demonstrate a cooperation between the intestinal tract and liver with the overproduction of serum and tissue TGs, early signs of metabolic syndrome. We anticipate an exacerbated condition if exposure is continued. This study provides a novel pathological reason for iAs exposure induced medical conditions related to metabolic syndromes. Overall design: Intestinal RNA was prepared from vehicle and iAs treated mice at 14-day-old (n=12), RNA from three mice were pooled, and a total four samples per group were used for RNA-sequencing.