Adult rats of various strains became obese when they were fed a highly palatable diet for several months. Analysis of their adipose tissue morphology revealed increases in both adipocyte size and number in most depots. Reintroduction of an ordinary chow diet to such animals precipitated a period of weight loss during which only mean adipocyte size returned to normal. Adipocyte number remained at the elevated level achieved during the period of weight gain. Thus, transient dietary obesity in rats results in a persistent obesity of a purely hyperplastic, nonhypertrophic form. Furthermore, the persistence of the cell number increase suggests that it is the result of proliferation or differentiation rather than of only an increase in the lipid content of a pool of very small and normally undetected adipocytes. An analysis of adipose tissue morphology changes during the course of diet-induced weight gain suggests that the achievement of some specific mean adipocyte size triggers the events that culminate in adipocyte number increase. What mechanisms may link adipocyte size to the formation of new adipocytes remains unknown.

Adjustment of litter size was used to provide two levels of early nutrition to rat pups and thereby to produce adult rats of markedly different body weights. Effects of the two levels of early nutrition on adipose tissue were compared after the rats had been fed ad libitum for nearly 1 year. Mean fat cell size did not differ between rats raised in large and small litters regardless of whether they had been maintained continuously on a stock diet (upon which rats usually have normal size fat cells) or had been switched to a high-fat diet (upon which rats usually have greatly enlarged fat cells). However, rats raised in large litters had less body fat and fewer fat cells than rats reared in small litters, both in absolute terms and relative to body weight. Litter size also affected the absolute, but not relative, increase in body fat and fat cell number induced by high fat feeding. Early nutrition thus has a sustained effect on fat mass and fat cell number, but not on fat cell size, which is apparent even when adipose tissue has been induced to major alteration by the feeding of a high fat diet.

An obesity syndrome was found in a number of mice infected as young adults with canine distemper virus, a morbillivirus antigenically related to measles. Body weights of obese animals 16 to 20 weeks after infection were comparable to those reported for genetically obese mice and for mice rendered obese by hypothalamic lesions. The total number of adipocytes in specific fat deposits was greater in obese animals than in their lean littermates. This hyperplasia was accompanied by moderate cell enlargement. Pancreatic islet tissue was also hypercellular in the obese mice. Brain tissue from the obese mice showed no overt pathology, and immunofluorescence staining for viral antigens was negative. There may be a selective, virus-induced disruption of critical brain catecholamine pathways.

Surgical removal of subcutaneous fat depots in weanling rats leads to a regenerative response. If the rats are fed a diet high in fat, adipose mass and adipocyte number are precisely restored within 7 months of surgery. Thus, under appropriate experimental circumstances, compensatory hyperplasia will occur in adipose tissues of the rat.

Lipectomized and sham-operated rats were fed a high-fat diet to induce hyperphagia and rapid fat accumulation. Lipectomized rats with 25% fewer adipocytes were less hyperphagic and accumulated less fat, but their adipocytes remained equal in size to adipocytes of controls. A role for adipocyte size in fat storage regulation and food intake control is postulated.