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Undernutrition in the Neonate: Long-term Effects upon Mitochondrial and Microsomal Constituents of the Rat Hepatocyte¹

Department of Pediatrics, University of California, San Francisco, California 94122

The immediate and long-term effects of undernutrition in nursing Wistar rats on the quantity and composition of microsomal and mitochondrial fractions of the hepatocyte were investigated. Rats were raised in small litters (SL) and large litters (LL) until 21 days of age and then weaned to a normal diet. Body and liver weights of LL rats increased at a slower rate and by 19 days of age were 50% of SL values; after weaning LL weights rose rapidly and eventually approached the SL values. The concentrations of microsomal protein, phospholipid, cytochrome b₅, cytochrome P-450 and activity of NADPH-cytochrome c reductase per gram liver in the LL group remained similar to the SL rats during the nursing period. After weaning, concentrations of microsomal enzymes in the LL group were increased. Thus, the total hepatic quantities or activities remained equal to those of the SL group, even when there was a discrepancy in weight. Mitochondrial protein, phospholipid, concentration of cytochromes c and a, and cytochrome oxidase activity per gram liver remained similar in both groups at any given age. Thus, during a period of general malnutrition, when limited availability of essential substrates is known to reduce the rate of cell proliferation, some subcellular structures and constituents associated with the differentiated functions of the cell remained essentially proportional to tissue weight. Similarly, during the period of recovery with institution of normal feeding, microsomal and mitochondrial constituents in LL animals were not decreased but remained equal to or exceeded concentrations in the animals raised in small litters.

² Recipient of U. S. Public Health Service Research Program Award HE 31766.

Manuscript received 23 November 1970.