Fat metabolism in protein malnutrition

ABSTRACT

The aim of this work was to make an assessment of the role of impaired lipoprotein secretion from the liver in the pathogenesis of the fatty liver caused by protein malnutrition in infants. The only evidence for this role prior to the study was that serum lipid levels were lower than normal in patients with fatty liver. The proposed method for measuring the incorporation of amino acids into the lipoproteins of children with fatty liver was used first with the rat as a model. It was found, in the development of such a model, that there are great variations in the level of liver fat induced by protein depletion in the rat. The variations depend on the age and nutritional state of the animal at the time of introducing the low-protein diet, and depend on the calorie intake while thay are on the diet. It was found that there were always measurable increases in the liver fat content when 70-gram rats were fed a 6 percent casein diet for 7 to 10 days. The use of this model with either single-injection or constant-infusion techniques showed that the incorporation of labelled amino acids into the serum lipoproteins was reduced. The greatest reduction was in the VLDL fraction of the low-density lipoproteins. There was no evidence for any significant contribution to the fatty liver from increased lipogenesis at the time when the defect in lipoprotein synthesis was apparent. The incorporation of methionine-S35 into the low-density lipoproteins of malnourished children was measured; although the changes were not consistent throughout the group studied, there was some evidence that the incorporation of the amino acid into lipoproteins was less when the children were malnourished than when they had recovered. Some modification in the design of future experiments of this type are discussed. Routine measurements of serum triglycerides in the patients during treatment showed that there are some differences between the pattern seen here and that reported elsewhere. The patients had very low triglyceride levels after recovery. These low levels were found to be due to the high fat content of the diet which the patients received during treatment. The changes in serum triglycerides induced by changing the fat content of the diet were found to be more rapid and to be relatively greater than any changes previously reported for adults. No explanation for this is given at present. The unusual patterns for serum triglycerides found during treatment of the malnourished patients with a low-fat diet appeared at first to be inconsistent with reduced synthesis of lipoprotein being associated with the fatty liver; other changes in fat metabolism concurrent with such a defect, however, could account for the unusual patterns.(AU)