METABOLISM OF LIPIDS IN KWASHIORKOR

Abstract

A study of lipid metabolism in Nigeria kwashiorkor children has shown that the serum phospholipids, total cholesterol, cholesterol esters and total fatty acid levels were low when compared with the values for control children, but there was no significant difference in the triglycerides level. A gas chromatographic analysis of the serum total fatty acids of the kwashiorkor group also showed a higher percentage of oleic acid and palmitic acid but lower linoleic arachidonic acids than in the control children. There were no significant differences in the percentages of palmitoleic acid and stearic acid. However, the absolute concentrations of stearic, linoleic and arachidonic acids were lower in the kwashiorkor group than in the control group. There was also a detectable amount of an unidentified acid in the serum of a few of the control children and in many of the kwashiorkor children. Two of the kwashiorkor children exhibited an abnormal fatty acid pattern different from the observed patterns of the renaming kwashiorkor children and of the control children.

Eight of the kwashiorkor children were admitted into a metabolic ward but three of them died during the first week in hospital. Serum lipids of those children were determined on admission and at ten days intervals for a period of thirty days. There was a significant increase in the serum Levels of the phospholipids, triglycerides, total fatty acids, total fatty acids, total cholesterol and cholesterol esters during the first ten days of treatment. This increase in the serum lipid was maintained until the twentieth day. Only the triglycerides and the total fatty acids levels had returned to the admission level by the thirtieth day, while the phospholipid, total cholesterol and cholesterol esters levels were still above the control level. The absence of any detectable concentration of cholesterol esters in two of the children who died led to a further study of cholesterol esters in different grades of kwashiorkor children. This study revealed that there was no significant difference in the ratio of cholesterol ester to total cholesterol in the mild, moderate and severe cases of kwashiorkor.

On the basis of the observed abnormal lipid metabolism in Nigerian kwashiorkor patients, albino rats were fed a diet similar in composition to that consumed by some Nigerian children who develop kwashiorkor, and the effects of this diet on lipid metabolism were studied. After feeding the rats for four months on the experimental diet, some of the characteristic features of kwashiorkor, such as retarded growth, silkiness of hair and fatty livers were observed.

Because the liver is the main organ for the metabolism of lipids and because the effect of the diet was more marked in this organ, a detailed analysis of its lipid content was carried out. The results of the analysis revealed that the accumulated fat in the livers of the rats on the experimental diet was mainly neutral lipids. A gas chromatographic analysis of the fatty acids of the polar and neutral lipids showed that the change in the liver total fatty acid pattern in the experimental rats was in the neutral lipids and not in the polar lipids. The liver lipids of the experimental rats had a higher percentage of oleic acid and lower percentages of linoleic and arachidonic acid than the control.

The mechanism whereby lipids accumulated in the liver of the rats on the experimental diet was investigated. When both the control and experimental rats were fed palnitic-1- 14C and linoloic-l-14C acids, there was a much higher incorporation of the labels into the liver total lipids of the experimental rats than in the control rats. The oxidation of the labeled acids into 14C02 showed that the rate of catabolism of palaitic-1- 14C was higher in the experimental rats but there was no significant difference in the catabolism of linoloic-1-14C. In vitro experiments using liver slices also showed a higher incorporation of acetate-1- 14C and glucose-U-14C into the total liver lipids of the experimental rats than in the control. The in-vitro incorporation of leucine-l-14C into liver proteins was also higher in the experimental rats.

The serum from fatty acids, total cholesterol, cholesterol esters, phospholipids and triglycerides level were higher in the experimental rats than in the control rats. When the results of this study were compared with those reported by other authors it was evident that the fatty liver observed in this study was not due to a deficiency of methionine, choline or essential fatty acids, and that the mechanism of formation of this fatty liver is different from that observed in previous studies.

A comparison of the metabolism of lipids in kwashiorkor children and in rats induced with a kwashiorkor-like syndrome was made. It was concluded that though the increased flux of serum free fatty acids into the liver and increased synthesis of lipids in the liver might not be the only factors in the pathogenesis of fatty livers in kwashiorkor but these appear important contributory factors.