Relationship of dietary intake to the development of glomerulosclerosis in obese Zucker rats

Obese Zucker rats are hyperphagic and develop premature glomerulosclerosis. The purpose of this study was to find out the effects of restriction of dietary intake on this glomerulosclerosis. The obese and lean male Zucker rats were fed with restricted amounts of balanced diet for periods of 40 and 50 weeks, sacrificed, and the body weight, the light and ultrastructural alterations of glomeruli, and the serum levels of blood urea nitrogen, triglyceride, and cholesterol were examined. Obese and lean male rats of identical ages were fed ad libitum with the diet and studied similarly. The dietary restriction significantly lessened the development of the glomerulosclerosis in obese rats, while those on the nonrestricted diet manifested an advanced glomerulosclerosis. The dietary restriction, however, did not normalize the obesity nor correct the elevated serum lipid level to the range of lean control rats. The spontaneous glomerular lesions of the obese rats were characterized by segmental mesangial expansion, disappearance of podocytes and endothelia, and obliteration of capillary lumina. The lean rats maintained essentially normal renal morphology. A similar study on the renal morphology done in female Zucker rats also revealed a preventive effect of dietary restriction on the development of glomerulosclerosis. In conclusion, there is a strong association between the glomerulosclerosis and the hyperphagia of the obese Zucker rats, both in males and females, and the emergence of this lesion is preventable to a significant degree.     

Intraventricular neuropeptide Y injections stimulate food intake in lean, but not obese Zucker rats.

We examined the effect of acute third intraventricular (IVT) injections of either saline or NPY (0.95, 3.0, 9.5, or 30.0 micrograms in 1 microliter) on the 1-, 4-, and 22-hour postinjection food and water intake of female obese (fa/fa), heterozygous lean (Fa/fa), and homozygous lean (Fa/Fa) Zucker rats. None of the doses of NPY had an effect on either food or water intake of fa/fa rats. A significant increase of food intake was seen in Fa/Fa rats at 1 and 4 hours after the 3.0 micrograms injection of NPY and at 1, 4, and 22 hours after the 9.5 micrograms injection of NPY. Both 3.0 and 9.5 micrograms of NPY also stimulated 1- and 4-hour postinjection food intake of Fa/fa rats, although this effect was significant only at 4 hours after the 3.0 micrograms dose. NPY had a less reliable effect on water intake; 3.0 micrograms of NPY stimulated 1-hour postinjection water intake of Fa/fa rats and 4-hour postinjection water intake of Fa/Fa rats. These results indicate that lean, but not obese Zucker rats, respond by eating more to centrally administered NPY. This deficit is similar to the effects seen with IVT insulin injections and may be a result of a common receptor-mediated mechanism.     

Increased sensitivity of Zucker obese rats to naloxone is present at weaning

Increased pituitary and plasma concentrations of opioid peptides in genetically obese rodents may be a cause or consequence of obesity. It has been shown that food intake is decreased more in adult genetically obese rats and mice than lean rats and mice by administration of naloxone, an opiate antagonist. Evidence for an opiate-mediated component in the development of rather than the consequence of obesity would be provided if young, not yet obese, genetically obese rats were more sensitive than lean rats to naloxone. In the present experiment two groups of male and female obese and lean Zucker rats, fasted for 2 hr before the onset of the dark portion of the 12-hr light-dark cycle, were administered 0.125 to 0.5 mg/kg naloxone or 0.5 to 2.0 mg/kg naloxone subcutaneously and 30- and 60-min food intakes were measured. In the group administered the lower doses of naloxone, obese rats of the three ages tested responded more than the lean rats after 30 min (70 vs. 79% of control, p less than 0.02). However, increased sensitivity occurred during the 0-60 min period in rats 4-5 weeks old and 0-30 min period in rats 8-9 and 12-13 weeks old. In the second group tested with the higher doses, the obese responded less than the lean rats (73 vs. 66% of control, p less than 0.05) and there was no difference in response after 0-60 min (66 vs. 61% of control, NS). Thus, increased sensitivity to threshold doses of naloxone occurs before the development of substantial obesity and therefore opiate peptides may play a causal role in obesity.     

Insulin stimulates inositol incorporation in hippocampus of lean but not obese Zucker rats

We have previously reported that intraventricular insulin is ineffective in decreasing the body weight of obese (fa/fa) Zucker rats. In the present study, we report that insulin at concentrations of 1 and 5 nM significantly stimulates incorporation of 3H-myoinositol into inositol phosphates (29 +/- 5% and 20 +/- 6% stimulation over control levels) and membrane inositol lipids (29 +/- 4% and 20 +/- 6% stimulation over control levels) within hippocampal slices from lean (Fa/Fa) Zucker rats (n = 3 preparations). Smaller but significant stimulations were observed in the Fa/fa Zucker rat (n = 5) hippocampus [10 +/- 3 and 13 +/- 4% stimulation over control levels (inositol phosphates) and 10 +/- 4 and 14 +/- 3% stimulation over control levels (inositol lipids) with 1 and 5 nM insulin]. Insulin had no effect on 3H-inositol incorporation into hippocampal slices from obese (fa/fa) Zucker rats (n = 5). No difference in insulin binding to hippocampal membranes was observed among the three genotypes. These findings confirm the behavioral observation of insulin insensitivity within the fa/fa Zucker CNS and suggest that this insensitivity may be gene-dose-related.     

Suppression of weight gain by glucagon in obese Zucker rats

Glucagon has been shown to lower blood lipids and to decrease food intake and body weight in short-term studies in man and animals. There is evidence of decreased secretion of glucagon in human obesity. The Zucker obese rat suffers from a genetic type of obesity and has an absolute reduction in circulating glucagon concentration. The effect of long-term administration of glucagon on the body weight in obese Zucker rats was studied. Glucagon caused a marked (-20%) reduction of body weight in obese Zucker rats with no change in feed intake. Urine glucose, urea nitrogen, creatinine, and ketone content, as well as serum triglyceride, cholesterol, alkaline phosphatase, creatinine, and insulin levels remained unchanged. Weights of perirenal fat, kidneys, and heart also remained unchanged. However, glucagon injection in obese Zucker rats caused significant decrease in serum glucose, and increases in SGOT, liver weight, and liver lipid and glycogen content. Further investigations are needed concerning the safety of chronic glucagon administration for weight control.     

Decreased pancreatic exocrine response to cholecystokinin in Zucker obese rats

Cholecystokinin (CCK), one of the peptides secreted by the gastrointestinal tract during a meal, stimulates release of enzymes into pancreatic juice and is a trophic hormone for the pancreas. Administration of CCK also decreases food intake, and obese rats have been shown to have a higher threshold than lean rats for this apparent effect on satiety. In this study experiments were designed to compare the sensitivity of obese and lean rats to the effects of CCK octapeptide (CCK-8) on pancreatic structure and exocrine function. In both growing and adult Zucker rats DNA content of the pancreas from obese rats was decreased compared with that from lean rats [2.42 +/- 0.21 vs. 3.07 +/- 0.18 mg (P less than 0.01) and 2.46 +/- 0.25 vs. 3.01 +/- 0.19 mg (P less than 0.05), respectively], and in adult obese rats this was accompanied by decreased pancreas size on both absolute weight and percent of body weight bases. In adult obese Bar Harbor mice, although DNA content of the pancreas was also decreased [1.70 +/- 0.10 vs. 2.41 +/- 0.11 mg (P less than 0.01)], pancreas weight was not different (0.30 +/- 0.01 vs. 0.32 +/- 0.01 g). In young rats growth of the pancreas was stimulated by 2 micrograms/kg CCK-8 administered subcutaneously or 100 mg/kg of a trypsin inhibitor administered orally twice daily for 2 wk. Although both treatments increased weight and DNA and protein content of the pancreas, the increases in DNA and protein content were smaller in obese than lean rats, indicating a decreased responsiveness to both trophic agents. Administration of CCK-8 stimulated smaller increases in pancreatic juice volume and amylase release in obese compared with lean rats, indicating decreased pancreatic exocrine function in response to CCK. In adults the CCK-8 dose-response curve for amylase release from dispersed pancreatic acini of obese rats was similar to that of lean rats, indicating normal sensitivity in vitro. Thus, in obese rats and mice DNA content of the pancreas is decreased when compared with that of lean rats and mice, and this is accompanied by decreased in vivo responses to CCK in obese rats.     

Interrelationships among activity,food intake and weight gain in genetically obese and lean Zucker rats

In Experiment 1, food deprivation resulting in a 30% reduction in body weight produced significant increases in wheel running in both obese and lean female Zucker rats. In Experiment 2, a new technique, food contingent activity (FR, VI), dramatically increased wheel running in both obese and lean female Zucker rats. This increase in activity was achieved primarily during the dark period. Regardless of changes in activity levels, food intake and body weight gain remained similar to controls. When food was again available ad lib, activity levels rapidly decreased for obese but not lean rats. These results indicate that behavioral interventions alone are not sufficient to correct the obesity of the genetically obese rat.     

Sympathoadrenal function in genetically obese Zucker rats.

The effects of genetic obesity on the actions and alterations of the sympathetic nervous system were studied in 10-12-month-old obese (fa/fa) and lean (Fa/-) Zucker rats. Blood glucose, plasma insulin, epinephrine (E), norepinephrine (NE), and free fatty acids (FFA) concentrations were measured in blood samples taken through a permanent heart catheter before, during, and after exercise or intravenous infusion of E and NE. Baseline plasma FFA and insulin levels were markedly increased in the obese animals. Exercise, i.e., strenuous swimming against a counter current for 15 min, led to reduction of plasma insulin concentrations and an increase of all other blood components in lean Zucker rats. In obese animals, an exaggerated increase of blood glucose and a large suppression of plasma insulin occurred. Plasma FFA levels tended to decline during exercise. Plasma catecholamine patterns in the exercising fatty Zuckers were not different to those of the lean animals. Infusion of E caused an increase of blood glucose and a decrease of plasma insulin concentrations in both groups of animals. The increase in blood glucose in the obese animals was significantly larger compared to the changes in the lean animals. Infusion of NE significantly reduced plasma insulin concentration in obese but not in lean animals. The results revealed that activation of the sympathetic system, expressed as exercise-induced alterations in plasma E and NE levels, is normal in obese Zucker rats. However, postsynaptic receptor effects of catecholamines on glycogenolysis and lipolysis are different in obese and lean animals, which points to permanent changes in adrenoceptor mechanisms on adipocytes, hepatocytes, and muscle cells in obesity.     

Impaired hypophagia induced by fecal anorexigenic substance in Zucker obese rats

Influence of fecal anorexigenic substance (FS-T) on feeding by Zucker obese rats was compared to that by their lean littermates and Wistar King A rats. FS-T, which has been found to suppress food intake mainly by activation of glucoreceptor neurons in the ventromedial hypothalamus, was injected intraperitoneally in a dose of 7 U/kg at 1930 hr, immediately before the dark period. Potency of FS-T in feeding suppression was much less in the obese rats than in their lean littermates or the Wistar King A rats. Meal size of the obese rats was decreased after the injection, but meal duration was unaffected. The suppressive effect on the lean rats and the Wistar King A rats included decrease of both size and duration of the meal. These results suggest that chemosensitivity in the ventromedial hypothalamus of Zucker obese rats may be impaired, which may be one explanation of the obesity in Zucker obese rats.     

Inhibition of food intake induced by acute stress in rats is due to satiation effects

Acute mild stress induces an inhibition of food intake in rats. In most studies, the cumulative daily food intake is measured but this only provides a quantitative assessment of ingestive behavior. The present study was designed to analyze the reduction in food intake induced by acute stress and to understand which behavioral and central mechanisms are responsible for it. Two different stressors, restraint stress (RS) and forced swimming stress (FSS), were applied acutely to male Wistar rats. We first measured corticosterone and ACTH in plasma samples collected immediately after acute RS and FSS in order to validate our stress models. We measured food intake after RS and FSS and determined meal patterns and behavioral satiety sequences. The expressions of CRF, NPY and POMC in the hypothalamus were also determined immediately after acute RS and FSS. The rise in corticosterone and ACTH levels after both acute RS and FSS validated our models. Furthermore, we showed that acute stress induced a reduction in cumulative food intake which lasted the whole day for RS but only for the first hour after FSS. For both stressors, this stress-induced food intake inhibition was explained by a decrease in meal size and duration, but there was no difference in ingestion speed. The behavioral satiety sequence was preserved after RS and FSS but grooming was markedly increased, which thus competed with, and could reduce, other behaviors, including eating. Lastly, we showed that RS induced an increase in hypothalamic POMC expression. These results suggest that acute stress may affect ingestive behavior by increasing satiation and to some extent by enhancing grooming, and this may be due to stimulation of the hypothalamic POMC neurons.     

Adaptation of lipid-induced satiation is not dependent on caloric density in rats

Food intake is modulated by ingestive (gastrointestinal) and post-ingestive signals; ingested fat is potent to produce short-term satiety (satiation) but this can be modified by long-term ingestion of a high fat diet. AIM: Determine whether altered lipid-induced satiation is dependent on the fat content of the diet, rather than increased caloric density or changes in adiposity. METHODS: Initial experiments determined the differences in the microstructure of meal patterns in rats fed a high fat diet (HF: 38% fat kcal) and in rats pair-fed an isocaloric, isonitrogenous low fat diet (LF: 10% fat kcal) and changes in meal patterns measured after long-term maintenance on the HF diet. RESULTS: Rats fed the HF diet had a significant 50% increase in meal frequency compared to rats fed the LF diet; in addition, there was a significant reduction in meal size (32%) and inter meal interval (38%) consistent with induction of satiation. After 8 weeks on the HF diet, these parameters tend to approach those of rats maintained on the LF diet. There was a significant 56% decrease in the activation of neurons in the NTS in response to intragastric gavage of lipid in rats maintained for 8 weeks on the HF compared to LF diet. CONCLUSION: Dietary fat alters meal patterns consistent with induction of a short-term satiety signal. This signal is attenuated with long-term exposure to dietary lipid, in the absence of ingestion of additional calories or changes in body weight. This adaptation of short-term satiety might contribute to diet-induced obesity.     

Skeletal muscle growth in lean and obese Zucker rats

Obese Zucker rats exhibit marked hyperphagia when compared to lean littermates but deposit a smaller percentage of total dietary energy as body protein. This study was designed to determine the roles of skeletal muscle protein synthesis, protein degradation, RNA, or DNA in producing the lower muscle mass of obese rats. At 44 days, 3 hindlimb muscles, the extensor digitorum longus (EDL), the gastrocnemius and the plantaris were significantly smaller in the obese animals. At 72 days, the differences in weights of these muscles were more pronounced. Protein synthesis and degradation were determined in the soleus at 44 days of age using an in vitro whole muscle incubation technique. Protein synthesis rate was significantly decreased in the obese animals. These changes were accompanied by reductions in both RNA and DNA levels. Significant changes in nucleic acid levels were observed in both the red and white portions of the gastrocnemius muscle. These changes in the anabolic process of protein accretion appear to be sufficient to account for the reduced muscle mass in the obese Zucker rat.     

Sensitivity to satiating and taste qualities of glucose in obese Zucker rats

A general "glucoreceptor" defect, demonstrable in pancreatic islet and taste cells, may contribute to the metabolic and taste abnormalities of adult onset diabetes and possibly, if present at the level of the hypothalamus, could produce hyperphagia and the obesity seen in diabetics. To determine if a glucoreceptor defect generally accompanies obesity and glucose intolerance, behavioral responsiveness to glucose was examined in nine obese and nine lean female Zucker rats. Daily food and fluid intake were measured during three two-bottle preference tests, in which rats chose between water and one of several glucose solutions (1%, 3%, and 12%). Taste responsiveness to glucose of obese rats appeared normal; however, increased satiating effects of glucose were found in obese rats, possibly due to an enhanced delivery of glucose to neurons that inhibit feeding, caused by glucose intolerance. Also, obese rats had (a) increased brain weights, and (b) increased volumes of ventromedial and paraventricular hypothalamic nuclei. These findings, perhaps explainable by an increased delivery of nutrients to the developing brain, indicate that the hyperphagia of Zucker rats is due neither to an overt hypothalamic lesion nor to insensitivity to glucose.     

Magnesium deficiency-induced anorexia in hyperphagic obese Zucker rats.

In clinical practice diabetes mellitus is the most significant cause of hypomagnesemia and Mg depletion. The obese Zucker rat approaches non-insulin-dependent type II diabetes; lean Zucker rats being suitable controls. Using this disease model the influence of dietary Mg deficiency was studied: animals received a diet providing only approximately 25 per cent of the Mg requirement; controls received drinking water fortified with Mg (16 mmol/L). During 125 days ad libitum feeding, Mg-deficient obese rats consumed nearly 50 per cent less feed pellets and gained 50 per cent less body weight than their obese counterparts. This effect was not fully reversible indicating Mg depletion. Blood glucose reflected food consumption, no glucosuria was detectable using test strips. In the heart muscle Mg was decreased and Ca increased in Mg-deficient rats indicating increased cardiac risk. When the rats were pair fed with lean Mg-deficient controls the development of obesity was prevented. Despite pronounced Mg deficiency blood glucose remained unaffected and no glucosuria was detectable. In future experiments the production of marginal Mg deficiency not inducing anorexia should be applied to study the pathogenetic role of Mg depletion in obese Zucker rats.     

Food intake response to modulation of secretion of cholecystokinin in Zucker rats

Exogenous administration of cholecystokinin (CCK) decreases food intake and elicits satiety behaviors. In the present experiments, feeding behaviors of Zucker obese and lean rats were measured in response to treatments that influence endogenous secretion of CCK from the duodenum. Secretion of CCK was increased by administration of phenylalanine, a stimulant of CCK release, and of trypsin inhibitor, which binds to trypsin, a negative-feedback signal for CCK release. Both of these treatments decreased the size of the first meal after a 6-h fast and average daily meal size and increased meal frequency. Administration of trypsin, proported to decrease secretion of CCK, increased average daily meal size and decreased meal frequency. Pancrease, a pancreatic enzyme concentrate, also hypothesized to act as a negative-feedback signal for CCK release, elicited feeding behaviors similar to those of trypsin. Thus the effects of these compounds on the feeding behavior of Zucker obese and lean rats may be related to their effects on CCK secretion. The feeding behaviors of obese rats were affected less than those of lean rats by exogenous administration of CCK, but in these experiments were affected more than in lean rats by modulation of endogenous release of CCK.     

Estrogen-induced suppression of intake is not mediated by taste aversion in female rats

Estrogen treatment can suppress the intake of a previously presented gustatory conditioned stimulus (CS). This finding has been interpreted as an estrogen-induced conditioned taste aversion. However, a distinction must be made between taste aversion and taste avoidance. In particular, tastes are only considered aversive if they elicit a stereotypic behavioral response, otherwise the reduction in intake is classified as an avoidance. Although aversive orofacial responses have been reported in male rats after taste-estrogen pairings, they have not been examined in ovariectomized female rats. The goal of the present investigation, then, was to use similar procedures to determine whether conditioned aversion also mediates the estrogen-induced reduction of intake in female rats. Animals were introduced to a novel 0.1% saccharin solution and immediately thereafter were given a subcutaneous injection of vehicle or estradiol benzoate (10 microg). Responses were assessed using a two-bottle preference test, a one-bottle acceptance test, and a taste reactivity (TR) test. The results confirmed previous reports of a reduced preference for saccharin after saccharin-estradiol pairing using the two-bottle test. The reduction in intake during the one-bottle test, however, was not accompanied by stereotypic aversive responses, such as gaping. Surprisingly, a similar reduction in intake also occurred when using a backward conditioning procedure in which estrogen was injected before, rather than after, CS access. Thus, the present results show that the suppressive effects of estrogen reflect an avoidance, rather than aversion and, moreover, that the reduced intake may be due to an unconditioned, rather than a conditioned, response.     

Hind leg heat balance in obese Zucker rats during exercise

 To analyse the effect of obesity on exercise-derived heat dissipation, lean and obese Zucker rats were exercised on an inclined treadmill until they would no longer run with gentle prodding. We measured their oxygen consumption, water vapour loss, the concentrations of adenosine tri- and diphosphate, creatine phosphate, and lactate in quick-frozen leg muscles, and the temperature of muscle, skin and blood in the aorta. We determined blood flow to leg muscle, fat and skin by measuring the entrapment of fluorescent microspheres. From the measurements we calculated heat flow rates between hind leg muscle, blood, fat and skin and the environment. The obese rats weighed twice as much as the lean (340–400 g and 175–200 g respectively) and ran half as fast (113 ± 7 m versus 257 ± 17 m). The differences between the two groups for basal oxygen consumption (lean: 6.7 ± 0.9 μmol/min, obese: 5.0 ± 1.9 μmol/min) and exercising oxygen consumption (lean: 37.8 ± 5.6 μmol/min, obese: 22.2 ± 3.8 μmol/min) were not significant. Both groups stopped running after the same time at their maximal speed (lean: 4.5 ± 0.3 min, obese: 4.2 ± 0.2 min). During exercise, lean rats had higher increases in core temperature (lean: 0.7°C, obese: 0.4°C) and muscle temperatures (lean: 1.3°C, obese: 0.7°C) than the obese rats. The calculated heat flows indicated a predominant conductive transfer of heat from muscle through the skin in lean rats but a higher proportion of heat transfer to the blood in obese rats. It is concluded that muscle heat accumulation did not cause fatigue in either case. Received: 30 July 1997 / Received after revision: 24 October 1997 / Accepted: 27 October 1997     

Feeding and drinking behavior responses of adult Zucker obese rats to cholecystokinin

Increased meal size in obese animals may occur because of decreased sensitivity to satiety factors. Feeding and drinking behavior responses of Zucker obese and lean rats to two forms of cholecystokinin (CCK), a putative satiety factor, were compared in these experiments. Octapeptide of CCK (CCK-8) in both obese and lean rats decreased meal size (47 and 65%) and rate of eating but not meal duration, and increased satiety ratio but not postmeal interval. Impure CCK decreased first meal size after a 6-hr fast similarly in obese and lean rats (33 and 40%, respectively); however, meal duration was decreased only in lean rats, and rate of eating was decreased only in obese rats. Postmeal interval was decreased in lean rats, while satiety ratio was increased only in obese rats. In spite of decreased first meal size daily food intakes were increased by both impure CCK and CCK-8 in lean rats. In 6-hr water-deprived rats injected with CCK-8, decreased water intake was associated with decreased food intake. However, while impure CCK in lean rats elicited similar responses as CCK-8, impure CCK in obese rats decreased food but not water intake. Feeding behavior response to the putative satiety agent, cholecystokinin, depended on form of the peptide administered and phenotype.     

Decreased sensitivity of Zucker obese rats to the putative satiety agent cholecystokinin

In obese rodents increased daily food intake leading to accumulation of adipose tissue is frequently accompanied by increased meal size and loss of the normal diurnal variations in feeding pattern. Increased meal size of obese rats may be due to decreased sensitivity to factors which elicit satiety. We compared Zucker obese and lean rat feeding behavior responses to octapeptide of cholecystokinin (OP-CCK), a peptide shown to decrease meal size in several species. Obese rats were less sensitive than lean rats to OP-CCK (.06, .25 and 1.0 μg/kg/meal) injected before each of four consecutive scheduled meals in the light portion of the diurnal cycle, when obese meal size was larger than lean. However, neither obese nor lean rats responded to injection of the same doses of OP-CCK during meals in the dark, when average meal size was larger than during the light and when average meal size of the obese rats was similar to that of lean rats. In both obese and lean rats injection of OP-CCK affected daily feeding pattern. Obese and lean Zucker rats are less sensitive to OP-CCK when meal size is larger, whether this is due to phase of the diurnal cycle (dark vs. light in both obese and lean rats) or phenotype (obese vs. lean rats in the light).     

Discrepancy between self-reported and actual caloric intake and exercise in obese subjects.

BACKGROUND AND METHODS. Some obese subjects repeatedly fail to lose weight even though they report restricting their caloric intake to less than 1200 kcal per day. We studied two explanations for this apparent resistance to diet--low total energy expenditure and underreporting of caloric intake--in 224 consecutive obese subjects presenting for treatment. Group 1 consisted of nine women and one man with a history of diet resistance in whom we evaluated total energy expenditure and its main thermogenic components and actual energy intake for 14 days by indirect calorimetry and analysis of body composition. Group 2, subgroups of which served as controls in the various evaluations, consisted of 67 women and 13 men with no history of diet resistance. RESULTS. Total energy expenditure and resting metabolic rate in the subjects with diet resistance (group 1) were within 5 percent of the predicted values for body composition, and there was no significant difference between groups 1 and 2 in the thermic effects of food and exercise. Low energy expenditure was thus excluded as a mechanism of self-reported diet resistance. In contrast, the subjects in group 1 underreported their actual food intake by an average (+/- SD) of 47 +/- 16 percent and overreported their physical activity by 51 +/- 75 percent. Although the subjects in group 1 had no distinct psychopathologic characteristics, they perceived a genetic cause for their obesity, used thyroid medication at a high frequency, and described their eating behavior as relatively normal (all P < 0.05 as compared with group 2). CONCLUSIONS. The failure of some obese subjects to lose weight while eating a diet they report as low in calories is due to an energy intake substantially higher than reported and an overestimation of physical activity, not to an abnormality in thermogenesis.