Cold acclimation of obese (ob/ob) mice: effects on skeletal muscle and bone

Obese (ob/ob) and lean mice at 4 weeks of age were housed at 23 degrees C or 14 degrees C for 4 or 8 weeks to determine effects of acclimation to mild cold on the growth of skeletal muscle, bone, and fat. Body weights at 12 weeks of age averaged 48 +/- 0.6 g and 27 +/- 1.9 g for obese mice housed at 23 degrees C and 14 degrees C and 29 +/- 0.5 g and 26 +/- 0.6 g and 26 +/- 0.6 g for lean mice housed at 23 degrees C and 14 degrees C, respectively. At 23 degrees C, muscle weights of obese mice were approximately 60% of those in lean mice. Muscles of obese mice did not grow during the first 4 weeks at 14 degrees C (4 to 8 weeks of age) but did show a small gain during the second 4 weeks (9 to 12 weeks of age) at 14 degrees C. As a result, by the end of 8 weeks at 14 degrees C, muscles of obese mice weighed only 35% to 45% as much as muscles of lean mice. Growth of the tibia and femur followed the same pattern as the muscles. Obese mice housed at 23 degrees C from 4 to 12 weeks of age contained about six times as much fat as lean mice at this age. Although exposure to 14 degrees C for 8 weeks depressed the accumulation of fat in obese mice, they still contained approximately three times the percentage body fat as lean counterparts.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of a warm environment on energy balance in obese (ob/ob) mice

Low rates of thermoregulatory heat production associated with low metabolic activity of brown adipose tissue, the primary site of thermoregulatory heat production, contribute substantially to the high efficiency of energy retention in obese (ob/ob) mice housed at 20 degrees C to 28 degrees C. To eliminate the need for thermoregulatory heat production lean and ob/ob mice were housed at 34.5 degrees C. At this temperature ob/ob mice still retained energy with a greater efficiency than lean littermates. Next, we investigated the possibility that the high efficiency of energy retention in ob/ob mice housed at 34.5 degrees C was related to depressed dietary-induced thermogenesis associated with low metabolic activity of brown adipose tissue. The sympathetic nervous system is a primary regulator of brown adipose tissue metabolism. Therefore, rates of norepinephrine (NE) turnover in brown adipose tissue, as an indicator of sympathetic nervous system stimulation of the tissue, were measured. Lean and ob/ob mice housed at 34.5 degrees C had equally low rates of NE turnover in their brown adipose tissue. Thus, the high efficiency of energy retention in ob/ob mice maintained at 34.5 degrees C is caused by factors other than low sympathetic stimulation of brown adipose tissue.     

Functional correlates of Na+,K+-ATPase in lean and obese (ob/ob) mice

Concentrations of Na+,K+-ATPase enzyme units are lower in skeletal muscle and liver of adult obese (ob/ob) mice than in their lean counterparts. The present studies were designed to provide information on functional correlates of Na+,K+-ATPase in ob/ob mice. Obese mice had lower potassium (K+) content in muscle and liver and higher sodium (Na+) content in muscle and liver and higher sodium (Na+) content in muscle than lean counterparts. The calculated intracellular Na+/K+ ratio in muscle of obese mice was approximately twice as high as in muscle of lean mice. Oxygen consumption was measured in mice maintained at 14 degrees, 25 degrees, or 33 degrees for 40 min and injected with 0.3 or 0.9 microgram ouabain per g body weight. Ouabain, a specific inhibitor of Na+,K+-ATPase, decreased oxygen consumption less in obese mice (12%--25%) than in lean mice (19%--38%). These results suggest that Na+ pump activity may be reduced in obese mice.     

Brown adipose tissue: contributions of nature and nurture to the obesity of an obese mutant mouse (ob/ob)

The aim of this investigation was to compare the contributions of the genotype of the brown adipose tissue (BAT) and of its environment to the obesity of the mutant mouse C57 BL/6J ob/ob. Pieces of interscapular BAT from lean or obese mice were transplanted to a site underneath the kidney capsule of recipient lean or obese mice. The grafts were left in place for 6 to 12 weeks and then examined by histological methods by electron microscopy to examine the ultrastructure of the mitochondria and by fluorescence histochemistry to examine the catecholaminergic innervation of the grafts. When lean BAT was grafted into obese mice, or when obese BAT was grafted into lean mice, kept at ambient temperatures, the characteristics of the donor BAT (i.e. lipid droplet size, mitochondrial ultrastructure and catecholaminergic innervation) transformed partially, but not completely, towards those of BAT in the host mouse. However, if lean mice containing obese BAT grafts were cold-acclimated at 4 degrees C or obese mice containing lean BAT grafts were warm-acclimated at 33 degrees C, the characteristics of the donor BAT transformed completely towards those of the BAT in the host mouse. This complete transformation occurred even if the host mice were returned to 23 degrees C after the period of temperature acclimation. Fluorescent histochemical observations indicated that the sympathetic innervation of BAT grafts was only indistinguishable from that of the lean or obese host BAT when the mice received a period of temperature acclimation (cold for lean mice; warm for obese mice). We conclude that BAT grafts from lean mice can assume the typical characteristics of BAT in obese hosts and that BAT grafts from obese mice can assume the typical characteristics of BAT in lean hosts provided that both the sympathetic innervation and the vascularization of the grafts is the same as in the host. Intrinsic properties of BAT in genetically obese mice are therefore unlikely to be of paramount importance in determining the obesity of the ob/ob mouse. Our results support the conclusions of other workers in implicating the low activity of the sympathetic innervation of BAT as being crucially important in causing the reduction of thermogenic activity.     

Fed and fasting thermoregulation in ob/ob mice

The body temperatures of mature lean and obese C57BL/6J mice were measured just after feeding, during ad libitum access to food, or every 24 h throughout a 3-day fast. Obese mice had body temperatures 1.0-1.4 degrees C lower than lean mice in the postprandial state and during ad libitum feeding. During food deprivation, obese mice became more hypothermic than lean sex-matched controls. A 5 degrees C fall in body temperature was observed in mutant females in the first 24 h of starvation, about twice that seen in any other experimental group. Over the same period the temperature changes of obese males and lean females were similar and both groups had larger hypothermic responses than lean males. The present results indicate that both genotype and gender affect thermoregulation in these mice. Under normal colony room conditions (ad libitum feeding, 23 degrees C) the ob/ob mutation is expressed by lower body temperatures which along with hypoactivity and hyperphagia account for the high rates of energy storage. When food availability is limited, females of both phenotypes display an increased capacity to reduce their maintenance energy requirements by lowering body temperatures. This hypothermia may be responsible for both the increased conservation of body mass seen during starvation and the slightly greater (5%) fat stores observed in female mice.     

Diurnal rhythm for corticosterone in obese (ob/ob) diabetes (db/db) and gold-thioglucose-induced obesity in mice

The present studies have examined the diurnal rhythm of corticosterone in genetically obese mice and in mice made obese by treatment with gold thioglucose. The values of corticosterone were significantly higher in the ob/ob mice than in lean mice at each of the four time points measured. The diurnal pattern for corticosterone in ob/ob mice, however, was similar to that in lean mice at both 6 and 12 weeks of age and had a nadir at 0700 h and a zenith at 1800 h. In mice with gold thioglucose-induced obesity, on the other hand, the corticosterone values were the same in the obese and lean control mice 6 weeks after treatment with gold thioglucose. By 12 weeks after gold thioglucose treatment, the obese animals had higher corticosterone levels in the morning than lean animals, but the peak values at 1800 h were not different. Restriction of body weight gain by allowing obese and lean mice food for only 4 h daily altered the pattern of corticosterone, but the values in the ob/ob mice remained higher than those in the lean mice. The corticosterone values of db/db mice housed at 24 C were significantly higher at 0800 and 1800 h than those in lean mice, and the diurnal rhythm was present, but smaller, in the db/db mice. In db/db and lean mice housed at an ambient temperature of 33 C, the corticosterone concentrations increased to the same values, and the diurnal rhythm was blunted in both. At the higher ambient temperature, the db/db mice gained weight more slowly, whereas the lean mice showed no weight gain.     

Effect of cold rearing on metabolic rate and growth rate of obese (ob/ob) mice

Oxygen consumption, total body mass, and body fat content were measured in lean and obese animals housed from birth at either 17 +/- 2 or 28 +/- 2 degrees C. Results for each of the three parameters were recorded at three time points 26, 35, and 56 days of age. The experiments demonstrate that at both ambient temperatures oxygen consumption expressed per kilogram body mass is consistently greater in lean animals. In all animals oxygen consumption (ml/kg/min) falls between 26 and 56 days, but significantly so in obese mice at 17 degrees C. There is no difference in age-related reduction of oxygen consumption between the genotypes at 28 degrees C; cold environment also significantly impairs growth of obese animals but not of lean ones. Contrary to those at 28 degrees C obese mice at 17 degrees C do not differ significantly in body weight from lean controls by 56 days of age. Carcass fat is consequently reduced in cold-reared obese mice compared to warm-reared obese, when expressed as grams of fat. When expressed as percentage fat, cold-reared lean and obese mice have less fat at 56 days.     

Acute effects of nicotine on plasma free fatty acid concentrations and on the response to cold stress, in lean and obese (genotype ob/ob) mice

Lean and genetically obese (ob/ob) male and female mice were given nicotine by subcutaneous injection. Nicotine treatment was found to raise plasma free fatty acids by similar amounts in both lean and obese mice. In lean mice, nicotine caused depression of rectal temperature at ambient temperatures 22-25 degrees C and partially prevented the hypothermia in these mice when exposed to cold (o-3 degrees C). In obese mice, nicotine treatment did not alter either rectal temperature at 22-25 degrees C or the severe hypothermia on cold exposure. It is proposed that the effect of nicotine on free fatty acids is due to release of adrenal catecholamines and that this mechanism operates in both lean and obese animals. It is also proposed that, in obese mice under normal circumstances, there is a defect in the central nervous control of this adrenergic mechanism which may contribute to the observed fall in body temperature at low ambient temperatures.     

Vitamin C supplementation decreases insulin glycation and improves glucose homeostasis in obese hyperglycemic (ob/ob) mice

The effects of dietary vitamin C supplementation on glucose homeostasis and insulin glycation were examined in adult lean and obese hyperglycemic (ob/ob) mice. In lean mice, supplementation of the drinking water with vitamin C (25 g/L) for 14 days did not affect food intake, fluid intake, glycated hemoglobin, plasma glucose, or plasma insulin concentrations. Total pancreatic insulin content and the percentage of glycated pancreatic insulin were also similar to control lean mice. In ob/ob mice, vitamin C supplementation caused significant reductions by 26% to 48% in food intake and fluid intake, glycated hemoglobin, plasma glucose, and insulin concentrations compared with untreated control ob/ob mice. The total insulin content and the extent of insulin glycation in the pancreas of ob/ob mice were also significantly decreased by 42% to 45% after vitamin C supplementation. This change was accompanied by a significant 80% decrease in the percentage of glycated insulin in the circulation of vitamin C-supplemented ob/ob mice. These data demonstrate that vitamin C supplementation can decrease insulin glycation and ameliorate aspects of the obesity-diabetes syndrome in ob/ob mice.     

Effect of adrenalectomy on the metabolism of glucose in obese (C57 B1/6J ob/ob) mice

The genetically obese mouse, C57 B1/6J ob/ob, has been suggested as an appropriate model for the study of obesity associated with diabetes mellitus. Employing glucose ¹⁴C(μl) as a tracer, the data presented here indicate that obese mice are able to clear glucose from the blood compartment at the same rate as their lean littermates. This was demonstrated with or without an associated cold glucose load. The abnormal glucose tolerance curves observed in the obese animals may be a result of secretion of glucose into the blood. Removal of the adrenal glands from the obese mice and their lean littermate does not impair their ability to clear a glucose load from the vascular compartment. The capacity for endogenous glucose secretion of ob/ob mice is severely curtailed by adrenalectomy, in that the glucose tolerance curves of these adrenalectomized animals become similar to those of sham-operated lean littermates. Thus, it appears that a considerable component of the hyperglycemia in ob/ob mice reflects major adrenal involvement that is activated by stress, ie, ether anesthesia and blood sampling. The hyperglycemia in ob/ob mice may reflect glucocorticoid-dependent gluconeogenesis.     

Islet amyloid polypeptide and insulin relationship in a longitudinal study of the genetically obese (ob/ob) mouse

Obese mice (Ume? ob/ob) and their lean litter-mates were investigated from 7 to 52 weeks of age with respect to the plasma concentration of islet amyloid polypeptide (IAPP) and insulin. Plasma levels of IAPP were highly elevated in the ob/ob mice and remained unchanged until age 33 weeks, after which a sudden significant increase occurred at age 40 weeks. The plasma concentration of insulin gradually increased from start to end and reached extremely high levels. In the lean mice, there were no age-related differences in plasma levels of IAPP and insulin, being of the same magnitude as in normal NMRI mice. The plasma IAPP/insulin molar ratio was similar in lean and obese mice until age 14 weeks. At 21 weeks, the ratio in the ob/ob mice had decreased dramatically and remained markedly (sixfold) lower than in the lean mice until the end of the study. The IAPP concentration in the pancreata of 21-week-old ob/ob mice was 25-fold higher than that in the lean mice. Immunohistochemically, a majority of the ob/ob mice displayed enlarged and more numerous pancreatic islets, compared with the lean mice, and the IAPP- and insulin-labeling intensity was equal for all animals. At the electron-microscopic level, there was an increase in the number of IAPP- and insulin-immunoreactive gold particles per whole granule area as well as per core granule area. We conclude that the dramatically increased IAPP levels in severely hyperinsulinemic ob/ob mice may be of importance for the development of insulin resistance. Further, the disproportionate secretion of IAPP and insulin in the adult obese mouse might indicate a disturbed negative feedback effect of IAPP on insulin secretory mechanisms, resulting in very high plasma insulin levels.     

Reduced hypothalamic neurotensin concentrations in the genetically obese diabetic (ob/ob) mouse: possible relationship to obesity

Hypothalamic tissue levels of nine regulatory peptides (bombesin, calcitonin gene-related peptide [CGRP], galanin, neuromedin B, neuropeptide Y [NPY], neurotensin, somatostatin, substance P, and vasoactive intestinal peptide [VIP]) were compared in Aston obese diabetic (ob/ob) and lean (+/?) mice aged 4, 16, and 28 weeks. Neurotensin concentrations were significantly lower in ob/ob mice than in lean mice, with a 20% reduction (P = .03) in the whole hypothalamus at 4 weeks of age, a 24% reduction (P = .009) in the lateral hypothalamus at 16 weeks, and a 50% reduction (P = .0007) in the central hypothalamus at 28 weeks of age. Apart from a 42% increase in vasoactive intestinal peptide concentrations in the central hypothalamus of ob/ob mice at 28 weeks (P = .02), levels of the other eight peptides examined did not differ significantly between obese and lean groups. Neurotensin is known to cause anorexia and increased energy expenditure when injected into the central hypothalamus. Reduced hypothalamic neurotensin concentrations may reflect reduced neurotensinergic activity, which might contribute to hyperphagia and decreased energy expenditure, two major defects that contribute to obesity and diabetes in the ob/ob syndrome.     

Effects of thyroxine on Na+,K+-ATPase and norepinephrine turnover in brown adipose tissue of obese (ob/ob) mice

Thyroxine treatment improves some of the defective thermogenic properties of obese (ob/ob) mice. Because brown adipose tissue (BAT) is an important thermogenic organ in mice, effects of thyroxine treatment on Na+, K+-ATPase, a thyroid-hormone responsive enzyme, and on rates of norepinephrine (NE) turnover, an indicator of sympathetic nervous system activity, in BAT of lean and obese mice were evaluated. Female mice, six weeks old, were injected with approximately 4 micrograms thyroxine daily for 2 weeks. Numbers of Na+, K+-ATPase enzyme units in BAT were similar in control lean and obese mice. Thyroxine treatment increased numbers of Na+, K+-ATPase enzyme units by 60% and 100% in lean and obese mice, respectively, indicating that the BAT of obese mice was responsive to thyroxine treatment. Fractional rates of NE turnover were 75% faster in BAT of control lean mice than in obese mice. Thyroxine treatment decreased functional rates of NE turnover in BAT of lean mice by 35%, but had no effect on NE turnover in BAT of obese mice. Rates of NE turnover in heart and pancreas of control lean and obese mice were unaffected by phenotype. Although the decreases in fractional rates of NE turnover in heart (-23%) and pancreas (-11%) of lean mice in response to thyroxine injections were not statistically significant, the calculated rates of NE turnover (fractional rate of NE turnover times the NE content of the organ) in these organs of lean mice were decreased 25% to 30% (P less than 0.05) in response to thyroxine. Thyroxine injections did not affect NE turnover in either heart or pancreas of obese mice.(ABSTRACT TRUNCATED AT 250 WORDS)     

Functional and histological characteristics of skeletal muscle and the effects of leptin in the genetically obese (ob/ob) mouse

BACKGROUND: Skeletal muscle mass in genetically obese (ob/ob) mice displays a reduced mass compared with their normal lean counterpart mice. However, the functional capacity of the available skeletal muscle mass in these animals has not yet been determined. OBJECTIVE: To investigate the properties of skeletal muscle in ob/ob mice and determine the effects of leptin administration on skeletal muscle in these mice. METHODS: Following 4 weeks of i.p. leptin administration (or control treatment) anaesthetized ob/ob and lean mice had their extensor digitorum longus and soleus muscles removed, and standard measures of isometric contractile properties and fatigability were performed. Histochemistry was used to determine fibre type proportions and individual fibre areas of all muscles. RESULTS: Leptin had no effect on the morphology or function of ob/ob skeletal muscle despite reducing body mass in ob/ob mice. Force production was unaltered in obese mice. However, a significant prolongation of contraction and relaxation times were evident. Obese skeletal muscle was also more fatigue resistant. Fibre proportions displayed a more slow type profile in ob/ob skeletal muscle, and in conjunction with previous work a reduced ability to hypertrophy. CONCLUSION: Skeletal muscle from obese mice is morphologically and functionally different from lean mouse skeletal muscle. Obese muscle is very similar to skeletal muscle from aged mice, and the specific contractile properties examined appear to be determined by the fibre make-up of these muscles.     

Potentiation of hyperphagia and relief of hypothermia in the genetically obese mouse (genotype, ob/ob) by alpha-methyl tyrosine.

DL-alpha-methyl-p-tyrosine methyl ester hydrochloride affected the hyperphagia and hypothermia characteristic of the genetically obese mouse (genotype, ob/ob) throughout an experimental period of 5 days. Intraperitoneal injections of 100 mg/kg body weight, daily, resulted in a significant increase in the average daily food consumption by 60 per cent, already elevated 35 per cent above that of lean litter-mates. The drug, administered at the same dose, caused a similar percentage elevation of food intake in the lean litter-mates. Rectal temperatures of obese mice were raised significantly throughout the 5-day period by an average of 0.95 degrees C, following administration of the drug. There was a significant rise of 0.75 degrees C in the rectal temperature of lean mice on 2 of the 5 days in the period. Body weight remained unchanged. Further experiments are necessary to determine the site of action at which DL-alpha-methyl-p-tyrosine brings about these effects at this dose in lean and obese mice.     

Abnormal thyroid hormone deiodination in tissues of ob/ob and db/db obese mice

To explore the relationships between thyroid hormone economy and defective thermogenesis in two genetically obese mouse strains, ob/ob and db/db, we measured iodothyronine deiodination in tissue homogenates and the T4 and T3 content of selected tissues. In lean mice acclimated at room temperature, type II 5'-deiodination in brown adipose tissue (BAT) homogenates rose 14.5-fold between 30 and 180 min of cold exposure at 4 C. In ob/ob mice kept at room temperature, type II 5'-deiodination rates in BAT homogenates were 2.29 times those in lean controls, but acute exposure to 4 C for 3 h caused a much smaller rise in 5'-deiodination in the ob/ob mice than in lean controls. Administration of 1 microgram/g norepinephrine caused similar elevations in BAT 5'-deiodination in ob/ob and lean mice. db/db mice had a defect in cold-stimulated BAT 5'-deiodination similar to that in the ob/ob mice in two of three experiments. In the obese animals of both strains, but not the lean mice, the magnitude of the rise in BAT type II deiodination after cold exposure was much greater in December than in warm months. Cerebrocortical homogenates from ob/ob mice had about 33% higher type II 5'-deiodination rates than those from lean controls, but showed normal type III T3 5'-deiodination. ob/ob liver homogenates had about 33% lower type I 5'-deiodination rates than controls. db/db, but not ob/ob, mice had lower serum T4 concentrations than controls. Both ob/ob and db/db mice had lower hepatic T4 concentrations than lean controls. The ob/ob animals had no alteration in brain T4 concentrations. Neither ob/ob or db/db mice had altered serum T3 concentrations, ob/ob mice had subnormal hepatic, but not brain, mean T3 concentrations. db/db mice also had reduced mean heptic T3 concentration. These results suggest that the subnormal cold-induced rise in ob/ob and db/db BAT type II 5'-deiodination is unrelated to thyroid status, perhaps being partly caused by defective sympathetic stimulation. This impaired deiodination response might result in subnormal intracellular T3 in BAT, thereby contributing to impaired thermogenesis. In contrast, the elevated cerebrocortical and unstimulated BAT type II deiodination and the decreased hepatic type I deiodination in the ob/ob mice are probably due to intracellular thyroid hormone deficiency.     

The development of obesity in genetically diabetic-obese (db/db) mice pair-fed with lean siblings

Summary The importance of reduced thermoregulatory thermogenesis as a mechanism for the high metabolic efficiency of the diabetic-obese (db/db) mouse has been investigated. Young db/db mutants were pair-fed to the ad libitum food intake of lean siblings for two weeks at two different environmental temperatures, 23 and 33 °C. At 23 °C, a temperature at which there is a substantial demand for thermoregulatory thermogenesis, the diabetic-obese animals deposited 51% more total energy and 75% more fat than the lean mice. At 33 °C (thermoneutrality) where there is no requirement for thermoregulatory heat, the mutants deposited 25% more fat than lean animals, but there was no significant difference in the total energy gain of the two groups. Pair-feeding resulted in a reduced protein deposition at both temperatures in the diabetic-obese animals compared to the lean. It is concluded that the high metabolic efficiency of the diabetic-obese mutant, like that of the obese (ob/ob) mouse, is caused by a low energy expenditure on thermoregulatory thermogenesis.     

Adrenalectomy reduces but does not reverse obesity in ob/ob mice

Bilateral adrenalectomy (ADX) of 4-month-old ob/ob mice led to reduced rates of body weight gain, a complete cessation of fat deposition and increased percentage carcass protein and ash during a 2-month observation period after surgery. However, ADX obese mice were still heavier and had more body fat and lower concentrations of carcass protein and ash than intact sex-matched littermate lean mice at the end of the experiment. When adrenalectomy was performed in younger obese mice before the syndrome was fully expressed (23 +/- 2 days of age), body weight gain was reduced by 40 per cent and fat deposition by 50 per cent during the next 3.5 months, but each was still greater than that of littermate lean mice. Despite the lower rate of weight gain after adrenalectomy, the skeletal and lean body growth of the early ADX obese mice equalled that of both obese and lean mice fed ad libitum. When the carcass composition of early ADX obese mice was compared with that of intact obese mice which were calorically restricted to the same rate of body weight gain, the ADX group had significantly less carcass fat (28 per cent) and more protein (50 per cent) and ash (20 per cent) than the dieted obese mice. In both experiments adrenalectomy led to reduced circulating immunoreactive insulin levels, although hyperinsulinemia persisted. The present results show that adrenalectomy is an effective tool for ameliorating the severity of many aspects of the ob/ob syndrome, particularly when compared with caloric restriction, but the procedure does not entirely reverse the deranged metabolism or abnormal carcass composition of these mice.     

Skeletal muscle accretion and turnover in lean and obese (ob/ob) mice.

Skeletal muscle growth in obese (ob/ob) and lean mice was estimated from changes in fat-free carcass weight during development. No differences were observed at 2 wk of age, but fat-free carcasses of obese mice weighed less than those of lean mice at 5 wk of age. Fat-free carcasses of the adult obese mice were only 78% as heavy as those of lean mice, although the obese mice weighed up to twice as much as the lean mice. Even though obese mice accumulated less muscle than lean mice, urinary creatinine output of the obese mice was equal to that of the lean mice. The amount of 3-methylhistidine (3MH) in the carcasses of the mice and urinary output of 3MH were used to calculate the fractional breakdown rate (FBR) of myofibrillar proteins. Accumulation of 3MH in the carcasses paralleled carcass weight gain; thus, obese mice accumulated less 3MH than lean mice. Urinary output of 3MH was measured from 5 to 37 wk of age and was as great in the obese as in the lean mice; consequently, the FBR of the myofibrillar proteins was faster in the obese than in the lean mice. The FBR averaged 8.5 ± 0.6%/day for obese mice and 5.0 ± 0.1%/day for lean mice. The rate of 3MH accumulation in the carcass and the FBR were subsequently utilized to calculate a fractional synthesis rate (FSR) for the myofibrillar proteins. The FSR was not reduced in obese mice. The results suggest that obese mice accumulate less muscle because the rate of muscle degradation is increased.     

Decreased food intake does not completely account for adiposity reduction after ob protein infusion.

The effects of recombinantly produced ob protein were compared to those of food restriction in normal lean and genetically obese mice. Ob protein infusion into ob/ob mice resulted in large decreases in body and fat-depot weight and food intake that persisted throughout the study. Smaller decreases in body and fat-depot weights were observed in vehicle-treated ob/ob mice that were fed the same amount of food as that consumed by ob protein-treated ob/ob mice (pair feeding). In lean mice, ob protein infusion significantly decreased body and fat-depot weights, while decreasing food intake to a much lesser extent than in ob/ob mice. Pair feeding of lean vehicle-treated mice to the intake of ob protein-treated mice did not reduce body fat-depot weights. The potent weight-, adipose-, and appetite-reducing effects exerted by the ob protein in ob protein-deficient mice (ob/ob) confirm hypotheses generated from early parabiotic studies that suggested the existence of a circulating satiety factor of adipose origin. Pair-feeding studies provide compelling evidence that the ob protein exerts adipose-reducing effects in excess of those induced by reductions in food intake.