{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T13:05:39Z","timestamp":1792069539693,"version":"4.4.0"},"reference-count":48,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2018,5,22]],"date-time":"2018-05-22T00:00:00Z","timestamp":1526947200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.3390\/nu10050653","type":"journal-article","created":{"date-parts":[[2018,5,23]],"date-time":"2018-05-23T03:14:24Z","timestamp":1527045264000},"page":"653","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Choline Supplementation Prevents a Hallmark Disturbance of Kwashiorkor in Weanling Mice Fed a Maize Vegetable Diet: Hepatic Steatosis of Undernutrition"],"prefix":"10.3390","volume":"10","author":[{"given":"Thaddaeus","family":"May","sequence":"first","affiliation":[{"name":"Childrens\u2019 Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, 1100 Bates Street, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin C.","family":"Klatt","sequence":"additional","affiliation":[{"name":"Division of Nutritional Sciences, Cornell University, Ithaca, NY 14853, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacob","family":"Smith","sequence":"additional","affiliation":[{"name":"University of Texas Rio Grande Valley School of Medicine, 1210 West Schunior Street, Edinburg, TX 78541, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eumenia","family":"Castro","sequence":"additional","affiliation":[{"name":"Childrens\u2019 Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, 1100 Bates Street, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Manary","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Washington University in St. Louis School of Medicine, 660 S. Euclid Ave., St. Louis, MO 63110, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie A.","family":"Caudill","sequence":"additional","affiliation":[{"name":"Division of Nutritional Sciences, Cornell University, Ithaca, NY 14853, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Farook","family":"Jahoor","sequence":"additional","affiliation":[{"name":"Childrens\u2019 Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, 1100 Bates Street, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8475-4704","authenticated-orcid":false,"given":"Marta L.","family":"Fiorotto","sequence":"additional","affiliation":[{"name":"Childrens\u2019 Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, 1100 Bates Street, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2018,5,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1016\/S0140-6736(13)60937-X","article-title":"Maternal and child undernutrition and overweight in low-income and middle-income countries","volume":"382","author":"Black","year":"2013","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1186\/s13690-015-0072-1","article-title":"Mortality and morbidity patterns in under-five children with severe acute malnutrition (SAM) in Zambia: A five-year retrospective review of hospital-based records (2009\u20132013)","volume":"73","author":"Munthali","year":"2015","journal-title":"Arch. Public Health"},{"key":"ref_3","unstructured":"Briend, A. (2014). Kwashiorkor: Still an Enigma\u2013The Search Must Go on. CMAM Forum Technical Brief, CMAM Forum."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1016\/S0140-6736(48)92087-X","article-title":"The essential pathology of kwashiorkor","volume":"1","author":"Davies","year":"1948","journal-title":"Lancet"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"714","DOI":"10.1111\/j.1749-6632.1954.tb36447.x","article-title":"The pathology of dietary liver disease in tropical Africa","volume":"57","author":"Davies","year":"1954","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_6","first-page":"346","article-title":"Fatty liver disease in infants in the British West Indies","volume":"263","author":"Waterlow","year":"1948","journal-title":"Med. Res. Counc. Spec. Rep. Ser. (Lond.)"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"568","DOI":"10.1093\/ajcn\/22.5.568","article-title":"Relation of Serum Lipids and Lipoproteins to Fatty Liver in Kwashiorkor","volume":"22","author":"Truswell","year":"1969","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1126","DOI":"10.1093\/ajcn\/81.5.1126","article-title":"Relation between liver fat content and the rate of VLDL apolipoprotein B-100 synthesis in children with protein-energy malnutrition","volume":"81","author":"Badaloo","year":"2005","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"106","DOI":"10.4314\/mmj.v21i3.45630","article-title":"Kwashiorkor: More hypothesis testing is needed to understand the aetiology of oedema","volume":"21","author":"Manary","year":"2009","journal-title":"Malawi Med. J."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"S207","DOI":"10.1093\/cid\/ciu485","article-title":"Environmental Enteric Dysfunction: Pathogenesis, Diagnosis, and Clinical Consequences","volume":"59","author":"Keusch","year":"2014","journal-title":"Clin. Infect. Dis."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1302","DOI":"10.1093\/jn\/133.5.1302","article-title":"Concentrations of choline-containing compounds and betaine in common foods","volume":"133","author":"Zeisel","year":"2003","journal-title":"J. Nutr."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1007\/BF02193854","article-title":"Influence of sulfur-amino acid content variation in plant vs. animal protein on serum and tissue lipids in rats","volume":"40","author":"Potter","year":"1990","journal-title":"Plant Foods Hum. Nutr. Dordr. Neth."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1111\/j.1740-8709.2006.00053.x","article-title":"The quality of the diet in Malawian children with kwashiorkor and marasmus","volume":"2","author":"Sullivan","year":"2006","journal-title":"Matern. Child. Nutr."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1526","DOI":"10.1111\/j.1440-1746.2006.04701.x","article-title":"Essential pathogenic and metabolic differences in steatosis induced by choline or methione-choline deficient diets in a rat model","volume":"22","year":"2007","journal-title":"J. Gastroenterol. Hepatol."},{"key":"ref_15","first-page":"1399","article-title":"Choline deficiency: A cause of hepatic steatosis during parenteral nutrition that can be reversed with intravenous choline supplementation","volume":"22","author":"Buchman","year":"1995","journal-title":"Hepatology"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2998","DOI":"10.1016\/S0021-9258(18)69166-5","article-title":"The active synthesis of phosphatidylcholine is required for very low density lipoprotein secretion from rat hepatocytes","volume":"263","author":"Yao","year":"1988","journal-title":"J. Biol. Chem."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/S0021-9258(19)50785-2","article-title":"The function of cytidine coenzymes in the biosynthesis of phospholipides","volume":"222","author":"Kennedy","year":"1956","journal-title":"J. Biol. Chem."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1475","DOI":"10.3945\/jn.111.138859","article-title":"Folate intake, MTHFR genotype, and sex modulate choline metabolism in mice","volume":"141","author":"Chew","year":"2011","journal-title":"J. Nutr."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/0163-7827(88)90005-7","article-title":"The methylation of phosphatidylethanolamine","volume":"27","author":"Vance","year":"1988","journal-title":"Prog. Lipid Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1016\/S0022-2275(20)37253-9","article-title":"Phosphatidylcholine biosynthesis is required for secretion of truncated apolipoprotein Bs from McArdle RH7777 cells only when a neutral lipid core is formed","volume":"38","author":"Vermeulen","year":"1997","journal-title":"J. Lipid Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"636","DOI":"10.1093\/ajcn\/68.3.636","article-title":"Determination of discretionary salt intake in rural Guatemala and Benin to determine the iodine fortification of salt required to control iodine deficiency disorders: Studies using lithium-labeled salt","volume":"68","author":"Rozendaal","year":"1998","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_22","first-page":"231","article-title":"The daily water, sodium and potassium excretion in urine of Ghanaian children aged 5 to 12 years","volume":"24","author":"Badoe","year":"2005","journal-title":"West Afr. J. Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"5269","DOI":"10.1113\/jphysiol.2014.279067","article-title":"Ribosome abundance regulates the recovery of skeletal muscle protein mass upon recuperation from postnatal undernutrition in mice","volume":"592","author":"Fiorotto","year":"2014","journal-title":"J. Physiol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2651","DOI":"10.1042\/bj0292651","article-title":"The action of choline and other substances in the prevention and cure of fatty livers","volume":"29","author":"Best","year":"1935","journal-title":"Biochem. J."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1093\/jn\/36.6.739","article-title":"Anemia and edema of chronic choline deficiency in the rat","volume":"36","author":"Engel","year":"1948","journal-title":"J. Nutr."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"730","DOI":"10.1080\/01621459.1974.10480196","article-title":"EDF Statistics for Goodness of Fit and Some Comparisons","volume":"69","author":"Stephens","year":"1974","journal-title":"J. Am. Stat. Assoc."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1080\/01621459.1974.10482955","article-title":"Robust Tests for the Equality of Variances","volume":"69","author":"Brown","year":"1974","journal-title":"J. Am. Stat. Assoc."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1093\/biomet\/38.3-4.330","article-title":"On the Comparison of Several Mean Values: An Alternative Approach","volume":"38","author":"Welch","year":"1951","journal-title":"Biometrika"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"99","DOI":"10.2307\/3001913","article-title":"Comparing Individual Means in the Analysis of Variance","volume":"5","author":"Tukey","year":"1949","journal-title":"Biometrics"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1016\/j.abb.2013.07.018","article-title":"Human choline dehydrogenase: Medical promises and biochemical challenges","volume":"537","author":"Salvi","year":"2013","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Ma, X., Lin, L., Qin, G., Lu, X., Fiorotto, M., Dixit, V.D., and Sun, Y. (2011). Ablations of ghrelin and ghrelin receptor exhibit differential metabolic phenotypes and thermogenic capacity during aging. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0016391"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1373\/49.2.286","article-title":"Determination of Choline, Betaine, and Dimethylglycine in Plasma by a High-Throughput Method Based on Normal-Phase Chromatography\u2013Tandem Mass Spectrometry","volume":"49","author":"Holm","year":"2003","journal-title":"Clin. Chem."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12963-015-0068-7","article-title":"Salt intakes in sub-Saharan Africa: A systematic review and meta-regression","volume":"14","author":"Oyebode","year":"2016","journal-title":"Popul. Health Metr."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Cho, C.E., Taesuwan, S., Malysheva, O.V., Bender, E., Tulchinsky, N.F., Yan, J., Sutter, J.L., and Caudill, M.A. (2017). Trimethylamine-N-oxide (TMAO) response to animal source foods varies among healthy young men and is influenced by their gut microbiota composition: A randomized controlled trial. Mol. Nutr. Food Res., 61.","DOI":"10.1002\/mnfr.201770016"},{"key":"ref_35","unstructured":"Golden, M.H. (1985). The consequences of protein deficiency in man and its relationship to the features of kwashiorkor. Nutr. Adapt. Man., 169\u2013185."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1111\/j.1469-7580.2006.00565.x","article-title":"Life-long protein malnutrition in the rat (Rattus norvegicus) results in altered patterns of craniofacial growth and smaller individuals","volume":"208","author":"Lobe","year":"2006","journal-title":"J. Anat."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1077","DOI":"10.1016\/j.jnutbio.2015.04.015","article-title":"Choline deficiency impairs intestinal lipid metabolism in the lactating rat","volume":"26","author":"Kelly","year":"2015","journal-title":"J. Nutr. Biochem."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"3386","DOI":"10.1093\/jn\/133.11.3386","article-title":"Phosphatidylethanolamine-N-methyltransferase activity and dietary choline regulate liver-plasma lipid flux and essential fatty acid metabolism in mice","volume":"133","author":"Watkins","year":"2003","journal-title":"J. Nutr."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"252","DOI":"10.3945\/jn.113.185389","article-title":"Choline Supplementation Protects against Liver Damage by Normalizing Cholesterol Metabolism in Pemt\/Ldlr Knockout Mice Fed a High-Fat Diet","volume":"144","author":"Castro","year":"2014","journal-title":"J. Nutr."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1016\/S0955-2863(98)00044-8","article-title":"Choline supplementation increases tissue concentrations of carnitine and lowers body fat in guinea pigs","volume":"9","author":"Daily","year":"1998","journal-title":"J. Nutr. Biochem."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1016\/j.molmet.2014.04.010","article-title":"Methyl-donor supplementation in obese mice prevents the progression of NAFLD, activates AMPK and decreases acyl-carnitine levels","volume":"3","author":"Dahlhoff","year":"2014","journal-title":"Mol. Metab."},{"key":"ref_42","first-page":"543","article-title":"Malnutrition induces gut atrophy and increases hepatic fat infiltration: Studies in a pig model of childhood malnutrition","volume":"5","author":"Lykke","year":"2013","journal-title":"Am. J. Transl. Res."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"42358","DOI":"10.1074\/jbc.M204542200","article-title":"An Unexpected Requirement for PhosphatidylethanolamineN-Methyltransferase in the Secretion of Very Low Density Lipoproteins","volume":"277","author":"Noga","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1998","DOI":"10.1194\/jlr.M300226-JLR200","article-title":"Insights into the requirement of phosphatidylcholine synthesis for liver function in mice","volume":"44","author":"Noga","year":"2003","journal-title":"J. Lipid Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"2197","DOI":"10.1093\/jn\/124.11.2197","article-title":"Severe folate deficiency causes secondary depletion of choline and phosphocholine in rat liver","volume":"124","author":"Kim","year":"1994","journal-title":"J. Nutr."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"18528","DOI":"10.1074\/jbc.M109.099333","article-title":"Specific contribution of methionine and choline in nutritional nonalcoholic steatohepatitis: Impact on mitochondrial S-adenosyl-l-methionine and glutathione","volume":"285","author":"Caballero","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Chiba, T., Suzuki, S., Sato, Y., Itoh, T., and Umegaki, K. (2016). Evaluation of Methionine Content in a High-Fat and Choline-Deficient Diet on Body Weight Gain and the Development of Non-Alcoholic Steatohepatitis in Mice. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0164191"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"E1531","DOI":"10.1152\/ajpendo.00668.2011","article-title":"Effects of methyl-deficient diets on methionine and homocysteine metabolism in the pregnant rat","volume":"302","author":"Wilson","year":"2012","journal-title":"Am. J. Physiol. Endocrinol. Metab."}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/10\/5\/653\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T15:05:22Z","timestamp":1760195122000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/10\/5\/653"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,5,22]]},"references-count":48,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2018,5]]}},"alternative-id":["nu10050653"],"URL":"https:\/\/doi.org\/10.3390\/nu10050653","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,5,22]]}}}