Long-term morphological and metabolic effects of early under- and over-nutrition in mice.

Milk intake of mouse pups was controlled by adjusting litter size at birth to four, nine or 20 pups. Litters of nine were considered as control groups. In adult animals many differences were seen among the three groups which had received the same diet ad libitum after weaning. Differences in body lipids largely accounted for the differences in body weight in both males and females. In parametrial adipose tissue, adipose cells, compared to those of controls, were enlarged and more numerous in mice from small litters, and smaller and less numerous in mice from large litters. After an overnight fast, the insulin response to glucose loading was highest in the obese group of mice, while it was absent in the lean group, suggesting permanent impairment in the secretion of insulin. Liver slices from animals which were bred in small litters incorporated more [U14C]-glucose into triglyceride moieties and cholesterol esters. Some of the metabolic changes in adipose tissue were related to cell size. With increasing litter size, glucose was incorporated into glycogen in muscle to a greater extent. Thus early feeding patterns induced permanent morphological, metabolic and hormonal changes in adults. Animals overfed in early life became obese and underfed animals remained lean when adults.