Effects of Early Life Oral Arsenic Exposure on Intestinal Tract Development and Lipid Homeostasis in Neonatal Mice: Implications for NAFLD Development.
| Autor: | Xiaojing Yang1, Weber, André A.1, Mennillo, Elvira1, Secrest, Patrick2, Chang, Max3, Wong, Samantha1, Le, Sabrina1, Junlai Liu4, Benner, Christopher W.3, Karin, Michael4, Gordts, Philip L. S. M.2, Tukey, Robert H.1, Shujuan Chen1 s18chen@health.ucsd.edu |
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| Předmět: |
*Animal populations
*Arsenic *Arsenic poisoning *Animal experimentation *RNA *Chromatographic analysis Lipid metabolism Infant development Sequence analysis Immunohistochemistry One-way analysis of variance Non-alcoholic fatty liver disease Hemostasis Comparative studies T-test (Statistics) Small intestine Statistical hypothesis testing Descriptive statistics Research funding Data analysis software Dietary fats Mice |
| Zdroj: | Environmental Health Perspectives. Sep2023, Vol. 131 Issue 9, p097001-1-097001-14. 14p. 3 Color Photographs, 4 Graphs. |
| Abstrakt: | BACKGROUND: Newborns can be exposed to inorganic arsenic (iAs) through contaminated drinking water, formula, and other infant foods. Epidemiological studies have demonstrated a positive association between urinary iAs levels and the risk of developing nonalcoholic fatty liver disease (NAFLD) among U.S. adolescents and adults. OBJECTIVES: The present study examined how oral iAs administration to neonatal mice impacts the intestinal tract, which acts as an early mediator for NAFLD. METHODS: Neonatal mice were treated with a single dose of iAs via oral gavage. Effects on the small intestine were determined by histological examination, RNA sequencing, and biochemical analysis. Serum lipid profiling was analyzed by fast protein liquid chromatography (FPLC), and hepatosteatosis was characterized histologically and biochemically. Liver X receptor-alpha (LXRα) knockout (퐿푥푟α-/-) mice and liver-specific activating transcription factor 4 (ATF4)-deficient (퐴푡푓 4Δ퐻푒푝) mice were used to define their roles in iAs-induced effects during the neonatal stage. RESULTS: Neonatal mice exposed to iAs via oral gavage exhibited accumulation of dietary fat in enterocytes, with higher levels of enterocyte triglycerides and free fatty acids. These mice also showed accelerated enterocyte maturation and a longer small intestine. This was accompanied by higher levels of liver-derived very low-density lipoprotein and low-density lipoprotein triglycerides, and a lower level of high-density lipoprotein cholesterol in the serum. Mice exposed during the neonatal period to oral iAs also developed hepatosteatosis. Compared with the control group, iAs-induced fat accumulation in enterocytes became more significant in neonatal 퐿푥푟α-/- mice, accompanied by accelerated intestinal growth, hypertriglyceridemia, and hepatosteatosis. In contrast, regardless of enterocyte fat accumulation, hepatosteatosis was largely reduced in iAs-treated neonatal 퐴푡푓 4Δ퐻푒푝 mice. CONCLUSION: Exposure to iAs in neonatal mice resulted in excessive accumulation of fat in enterocytes, disrupting lipid homeostasis in the serum and liver, revealing the importance of the gut–liver axis and endoplasmic reticulum stress in mediating iAs-induced NAFLD at an early age. [ABSTRACT FROM AUTHOR] |
| Databáze: | GreenFILE |
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