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The effects of high fat and high carbohydrate diets on the development of body composition and oxygen consumption of genetically obese (C57BL/6Jobob) mice and non-obese (non-ob/ob) littermates are reported. The genotype of individual mice was identified on day 18 on the basis of values of oxygen consumption. Both non-ob/ob and ob/ob mice were fed ad libitum with either a high carbohydrate or high fat diet, which were identical in energy and protein content, from weaning on day 21 until 42 days of age. The non-ob/ob mice did not exhibit differences in food consumption when fed either diet. By day 42 the total protein and ash accretion of the non-ob/ob mice were similar when fed both diets while the total lipid accretion was decreased with the high fat diet. The ob/ob mice exhibited an increased food consumption when fed the high fat diet and deposited more total protein, lipid and ash by day 42 than the high carbohydrate fed ob/ob mice. Oxygen consumption of the mice was determined at days 21, 24, 28, 35, and 42, as well as day 18. The oxygen consumption of all the mice tended to decrease from day 21 to day 42. The decrease in oxygen consumption was significant only for the carbohydrate-fed males of both genotypes from day 21 to day 24. The high carbohydrate diet also tended to decrease the oxygen consumption among the females of both genotypes. The high fat diet tended to raise the postweaning values of oxygen consumption of both non-ob/ob and ob/ob male mice towards the preweaning values. This suggests that the usually observed postweaning reduction in oxygen consumption may be attributed to the shift from a high fat to a high carbohydrate diet, as well as other developmental changes that occur at weaning. In general, the high fat-fed mice tended to consume more oxygen than the high carbohydrate-fed mice. The increased oxygen consumption may be related to increased oxidation of total energy. The changes in the body composition of non-ob/ob mice reflect the increased energy expenditure of the high fat-fed non-ob/ob mice. J. Nutr. 108: 1491-1500, 1978.

This study was designed to determine if treadmill training of the male obese Zucker rat could reverse its deficit in muscle accretion, expose a possible latent defect in its muscle oxidative capacity or significantly alter its food intake and lipid deposition. At 12 wk of age muscle mass and myofibrillar protein concentration were significantly lower and body lipid and food intake were significantly higher in the sedentary obese than in the nonobese rat. Exercise, by both inducing hypophagia and increasing energy output, led to a lower body weight, body lipid, and muscle mass in the exercised than in the nonexercised rats. This response to exercise did not differ between both phenotypes, except for body lipid. In that case the reduction of body lipid was greater for the obese rats. Muscle mitochondrial enzyme activities and rates of mitochondrial respiration in the obese rats were not different or greater than those of their sedentary or pair-exercised nonobese counterparts. Taken together these data indicate that oxidative capacity per unit of muscle is not significantly lower in the obese rats than in nonobese rats in both sedentary and exercised states, but that total muscle oxidative capacity is lower on a whole-animal basis since total muscle mass is lower. Further, exercise reduces, but does not prevent the enhanced weight gain and lipid accretion that characterizes the obese rat.

Non-fa/fa and fa/fa rats were weaned at 18 days of age and fed either a high fat or high carbohydrate diet. At 6 weeks of age some of the rats fed high fat were fed the high carbohydrate diet until 10 weeks of age. Food consumption was equalized between all treatment groups. Epididymal fat pads were heavier in the fa/fa rats in all treatment groups. Fat pad weight and cellularity increased in the non-fa/fa rats fed the high fat diet. Cellularity was actually less in the fa/fa than in the non-fa/fa rats, but high fat feeding resulted in higher proportions of larger adipocytes in both phenotypes. Rates of epididymal fat pad lipogenesis and enzymatic activities were similar in both non-fa/fa and fa/fa rats in all treatment groups. Hepatic fatty acid synthesis and enzymatic activities were consistently greater in the fa/fa rats. Carbohydrate feeding resulted in increased hepatic fatty acid synthesis regardless of the earlier feeding of the fat diet, but the fa/fa rats were more responsive to the carbohydrate diet than the non-fa/fa rats. A delay in introduction of carbohydrate to the diet did not alter the eventual lipogenic capacity of fa/fa rats. Lipogenesis appeared responsive to the most recent diet.

Circadian rhythms were studied in ad libitum- and meal-fed Zucker rats. Lean and obese female rats were fed ad libitum or in a single meal from 1400–1800 for 12 d. Both groups of ad libitum-fed rats exhibited a nocturnal feeding pattern; obese rats ate more than the lean rats during the light and dark parts of the cycle. After 12 d, groups of rats were killed at 4-h intervals over a 24-h period, inclusively, and the presence of circadian rhythms was evaluated for the serum metabolites, liver constituents and the liver lipogenic enzymes. The obese ad libitum-fed rats demonstrated rhythms for serum triglycerides, serum cholesterol, liver protein and glycogen, and the activities of fatty acid synthetase, citrate cleavage enzyme (EC 4.1.3.8), and glucose-6-P dehydrogenase (EC 1.1.1.49). Meal feeding the obese rats modified the rhythms for serum cholesterol, liver glycogen and the activities of glucose-6-P dehydrogenase, and citrate cleavage enzyme and a rhythm was established for serum glucose. The feeding schedule did not cue a rhythm for serum tir-glycerides and phosphogluconate dehydrogenase (EC 1.1.1.44) or modify the rhythm for liver protein. The lean ad libitum-fed rats displayed rhythms for all the measured parameters except serum glucose. Feeding-cued rhythms for all metabolites except serum cholesterol were observed when the lean rats were meal-fed. These data suggest that the rhythms of the ad libitum-fed obese rats may not be similar to those observed in the lean rat. Yet, changing the feeding schedule may be important in establishing rhythm patterns that will alter the anabolic profile characteristic of the Zucker obese rat.

Effects of obesity and age on copper, iron, zinc, sodium, potassium, and protein were compared in liver, kidney, brain, and muscle of obese (fa/fa) and nonobese (non-fa/fa) male Zucker rats. Blood plasma cerulopasmin, copper, zinc, sodium, and potassium were also determined. Mean brain weight of fa/farats was less than that of non-fa/farats at 12 weeks of age; mean brain protein concentration was greater in fa/fathan in non-fa/faat 5 and 12 weeks of age. At 18–19 days of age, mean sodium concentration (mg/g protein) in liver of fa/fawas less than that of non-fa/fa.At 5 weeks of age, mean copper concentration (μg/g protein) in kidney was greater in fa/fa.Mean total copper, iron, zinc, sodium, and potassium in liver and kidney were greater in fa/fathan in non-fa/faat 5 weeks because of the larger livers and kidneys of fa/fa.Mean concentrations of copper, zinc, sodium, and potassium per gram of brain protein were slightly (6–10%) less in fa/fathan in non-fa/faat 5 weeks. By 12 weeks, mean concentrations of copper in liver, kidney, (tibialis) muscle, and blood plasma, ceruloplasmin in blood plasma, zinc in liver and muscle, iron in muscle, and sodium in liver were greater in fa/fathan in non-fa/fa.However, total amount of each mineral in muscle at 12 weeks was less in fa/fathan in non-fa/fabecause of the smaller mean muscle weight of fa/fa.Mean concentrations of copper and zinc in brain and of iron in liver and brain were less in fa/fathan in non-fa/faat 12 weeks. The major age-related changes in fa/fathat were not observed in non-fa/fawere large increases in liver and kidney copper between 5 and 12 weeks of age. It seems that the abnormal mineral metabolism is a consequence of the obesity, but the mechanisms are not identified.

The reliability of using oxygen consumption for the detection of ob/ob mice, among the progeny of heterozygote crosses, prior to the phenotypic expression of obesity was ascertained. Differences between obese and thin siblings that were great enough for predicting purposes were observed only after weaning. At 23 days of age ob/ob mice were identified on the basis of their individual oxygen consumption with 90% reliability. The ability to predict a pre-obese condition makes possible the differentiation of metabolic alterations preceding obesity from those that subsequently develop.We are grateful to Dr. G. H. Fried for supplying a prototype of the special Warburg flask, to Mr. G. Lolas for technical assistance, and to Mrs. M. Ritchey for typing the manuscript.