4.7 Article

Choline Supplementation Prevents a Hallmark Disturbance of Kwashiorkor in Weanling Mice Fed a Maize Vegetable Diet: Hepatic Steatosis of Undernutrition

Journal

NUTRIENTS
Volume 10, Issue 5, Pages -

Publisher

MDPI
DOI: 10.3390/nu10050653

Keywords

kwashiorkor; malnutrition; hepatic steatosis; fatty liver disease; choline; betaine; methionine; trimethylamine N-oxide (TMAO); one carbon metabolism; methylation

Funding

  1. USDA ARS
  2. Texas Medical Center Digestive Diseases Center (NIH) [P30 DK-56338]
  3. Children's Nutrition Research Center
  4. USDA CRIS [6250-51000-051-00D-1, 58-3092-5-001, 25-3471-5-302]
  5. NIH [DK56338, CA125123]
  6. CPRIT [RP150578]
  7. Dan L. Duncan Comprehensive Cancer Center
  8. John S. Dunn Gulf Coast Consortium for Chemical Genomics
  9. [T32-HD071839-05]
  10. [T32-HD-087137]

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Hepatic steatosis is a hallmark feature of kwashiorkor malnutrition. However, the pathogenesis of hepatic steatosis in kwashiorkor is uncertain. Our objective was to develop a mouse model of childhood undernutrition in order to test the hypothesis that feeding a maize vegetable diet (MVD), like that consumed by children at risk for kwashiorkor, will cause hepatic steatosis which is prevented by supplementation with choline. A MVD was developed with locally sourced organic ingredients, and fed to weanling mice (n = 9) for 6 or 13 days. An additional group of mice (n = 4) were fed a choline supplemented MVD. Weight, body composition, and liver changes were compared to control mice (n = 10) at the beginning and end of the study. The MVD resulted in reduced weight gain and hepatic steatosis. Choline supplementation prevented hepatic steatosis and was associated with increased hepatic concentrations of the methyl donor betaine. Our findings show that (1) feeding a MVD to weanling mice rapidly induces hepatic steatosis, which is a hallmark disturbance of kwashiorkor; and that (2) hepatic steatosis associated with feeding a MVD is prevented by choline supplementation. These findings support the concept that insufficient choline intake may contribute to the pathogenesis of hepatic steatosis in kwashiorkor.

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