Choline supplementation prevents a hallmark disturbance of kwashiorkor in weanling mice fed a maize vegetable diet: Hepatic steatosis of undernutrition

Authors: MAY, THADDEUS - Children'S Nutrition Research Center (CNRC); KLATT, KEVIN - Cornell University; SMITH, JACOB - University Of Texas Rio Grande Valley; CASTRO, EUMENIA - Children'S Nutrition Research Center (CNRC); MANARY, MARK - Washington University School Of Medicine; CAUDILL, MARIE - Cornell University; JAHOOR, FAROOK - Children'S Nutrition Research Center (CNRC); FIOROTTO, MARTA - Children'S Nutrition Research Center (CNRC)

Submitted to: Nutrients
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/16/2018
Publication Date: 5/22/2018
Citation: May, T., Klatt, K.C., Smith, J., Castro, E., Manary, M., Caudill, M.A., Jahoor, F., Fiorotto, M.L., 2018. Choline supplementation prevents a hallmark disturbance of kwashiorkor in weanling mice fed a maize vegetable diet: Hepatic steatosis of undernutrition. Nutrients. 10:653. https://doi.org/10.3390/nu10050653.
DOI: https://doi.org/10.3390/nu10050653

Interpretive Summary: Kwashiorkor is a severe form of childhood malnutrition that is characterized by the presence of edema and a fatty liver. The diets of these children are largely vegetable based and provide insufficient protein and numerous other micronutrients. In order to better understand the role of specific nutrients in the etiology of this condition, we formulated a diet from ingredients similar to those consumed by children who develop kwashiokor and fed it to young mice. The mice grew poorly and rapidly developed a fatty liver. However, when choline, one of the nutrients that is inadequate in this diet, was included in the diet the fatty liver did not occur. These results suggest that choline deficiency may contribute to the development of the fatty liver in kwashiorkor.

Technical Abstract: 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.