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

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.

Embryonic protein undernutrition by albumen removal programs the hepatic amino acid and glucose metabolism during the perinatal period in an avian model.

Different animal models have been used to study the effects of prenatal protein undernutrition and the mechanisms by which these occur. In mammals, the maternal diet is manipulated, exerting both direct nutritional and indirect hormonal effects. Chicken embryos develop independent from the hen in the egg. Therefore, in the chicken, the direct effects of protein deficiency by albumen removal early during incubation can be examined. Prenatal protein undernutrition was established in layer-type eggs by the partial replacement of albumen by saline at embryonic day 1 (albumen-deprived group), compared to a mock-treated sham and a non-treated control group. At hatch, survival of the albumen-deprived group was lower compared to the control and sham group due to increased early mortality by the manipulation. No treatment differences in yolk-free body weight or yolk weight could be detected. The water content of the yolk was reduced, whereas the water content of the carcass was increased in the albumen-deprived group, compared to the control group, indicating less uptake of nutrients from the yolk. At embryonic day 16, 20 and at hatch, plasma triiodothyronine (T3), corticosterone, lactate or glucose concentrations and hepatic glycogen content were not affected by treatment. At embryonic day 20, the plasma thyroxine (T4) concentrations of the albumen-deprived embryos was reduced compared to the control group, indicating a decreased metabolic rate. Screening for differential protein expression in the liver at hatch using two-dimensional difference gel electrophoresis revealed not only changed abundance of proteins important for amino acid metabolism, but also of enzymes related to energy and glucose metabolism. Interestingly, GLUT1, a glucose transporter, and PCK2 and FBP1, two out of three regulatory enzymes of the gluconeogenesis were dysregulated. No parallel differences in gene expressions causing the differences in protein abundance could be detected pointing to post-transcriptional or post-translational regulation of the observed differences.

Acetylator status of kwashiorkor children in Ibadan (south-west Nigeria).

Acetylator status was determined in 25 kwashiorkor children, aged between 8 months and 3 years and in 25 age-matched control group of healthy children after a single oral dose of sulphamethazine (40 mg/kg body weight) and by measuring the acetylated sulphamethazine in blood samples, collected 6 h after the administration of sulphamethazine. The percentage of slow acetylators among kwashiorkor children was 40% while among the control group of children it was 48%. The difference between the two groups was not significant. Therefore, it is probable that the slow acetylator status of the Nigerian African children may not be a contributing factor for the development of kwashiorkor, a syndrome of protein-energy malnutrition. Furthermore, the polymorphic activity of N-acetyl transferase enzyme may not be impaired in kwashiorkor.

Increased frequency of induced sister chromatid exchanges in kwashiorkor.

The study included 16 infants with advanced manifestations of kwashiorkor and 16 unrelated age-matched normals as controls. Whole blood samples, at room temperature, were exposed to gamma-rays in increasing dosages. Lymphocytes were cultured; phytohaemagglutinin and bromodeoxyuridine (10 microM) were added, at initiation of culture, and harvesting was performed after 64 to 68 h. Slides were coded and sister chromatid exchanges (SCE) counted. In controls, no significant increase in the frequency of SCE was found. For kwashiorkor infants the SCE frequencies showed significant increase as irradiation dosages rose. It is concluded that the changes observed are probably due to alteration in: the cell cycle length; activities of enzymes responsible for DNA repair; DNA growing points; and protection of cells from chromosome breakage.

UV-induced chromosome aberrations, sister-chromatid exchanges and cell survival in cultured lymphocytes from malnourished children.

Cultured lymphocytes from children with kwashiorkor and from normal children were examined for their susceptibility to ultraviolet (UV)-induced chromosome aberrations, sister-chromatid exchanges and cell survival. Cells from kwashiorkor exhibited increased chromosome aberrations, but not sister-chromatid exchanges, when exposed to higher doses of UV. Furthermore, when cells from these patients were exposed to higher doses of UV, there was a significant reduction in viability. These results indicate that, as compared to normals, cells from kwashiorkor were more sensitive to the lethal effects of UV.

Sister chromatid exchanges in protein-energy malnutrition.

The frequency of sister chromatid exchanges in children suffering from severe protein-energy malnutrition was investigated by the fluorescent-plus-Giemsa method. Children suffering from kwashiorkor had significantly higher mean SCEs per circulating lymphocyte than did normal children. A small but statistically significant decrease in these levels was observed following nutritional rehabilitation.

Long-term effects of kwashiorkor on the electroencephalogram.

The long-term effects of kwashiorkor on the electroencephalogram were assessed by means of computer analysis techniques. The experimental group, consisting of 30 black children, 6 to 12 years old, hospitalized for the treatment of kwashiorkor during the first 27 months of life, was age-matched with three control groups. These were a group of siblings and of yardmates, neither of whom had been exposed to acute infantile malnutrition, and a very high socioeconomic group of white children. The results revealed significantly less alpha activity and more slow-wave activity in the electroencephalogram of the kwashiokor group than in those of the control groups. These findings confirmed previous results based on visual analysis procedures.

Evaluation of domicilliary management of protein-calorie malnutrition.

An approach to tackle protein-calorie malnutrition through domiciliary management is described. Children suffering from moderate and severe protein-calorie malnutrition were managed using a food supplement containing low cost locally available foodstuffs and nutrition education. An evaluation showed that the anthropometric improvement was closely associated with better concepts in nutrition and improved dietary practices following nutrition education. Parents of children suffering from kwashiorkor had better knowledge and practice compared with those of marasmus.