Figure 1.

Study design. Male and female C57BL/6J (WT) and As3mt-knockout (KO) mice were fed a purified low-fat diet (LFD) with adequate folate content ($2\mathrm{mg}/\mathrm{kg}$) and drank deionized water for 4 weeks after weaning. Baseline metabolic characteristics were assessed prior to exposure to inorganic arsenic (iAs) by measuring fasting blood glucose (FBG) and by intraperitoneal glucose tolerance test (IPGTT). Mice were then exposed to 0 or $100\text{ppb}$ iAs in drinking water and consumed either a low ($0.2\mathrm{mg}/\mathrm{kg}$) or high ($10\mathrm{mg}/\mathrm{kg}$) folate LFD diet for the next 24 weeks. After 24 weeks, all animals were fed a purified high-fat diet (HFD) with the same low and high folate levels and continued iAs exposure for additional 13 weeks, followed by sacrifice and tissue collection. Metabolic phenotyping, including FBG, IPGTT, fasting plasma insulin (FPI) and assessment of body composition by magnetic resonance imaging (MRI), was conducted at Week 6, Week 24, and/or after 8 weeks on the HFD. Spot urine samples and livers for As speciation analysis were collected at Week 6 and/or at sacrifice. ^aN, number of mice at the beginning of the study.