Resting oxygen consumption in over- and underfed rats with lateral hypothalamic lesions

Rats maintaining stable, reduced body weights following lateral hypothalamic (LH) lesions were given either ad lib amounts of a palatable liquid diet or restricted amounts of a hydrated chow diet. The palatable diet produced weight gains while the diet restriction led to weight reductions in both LH- and sham-lesioned rats. Body composition analysis indicated that these changes in body mass were accounted for largely by changes in carcass fat. Resting oxygen consumption (expressed relative to body weight raised to the 3/4 power) was altered by both dietary regimens. Resting oxygen consumption in sham-lesioned rats increased by 5% following overfeeding and decreased by 13% following food restriction. LH-lesioned rats made similar responses to these dietary challenges. Overfed LH-lesioned rats increased their rate of resting oxygen consumption by 11%. Underfed LH-lesioned rats decreased oxygen consumption by 11%. These findings provide further evidence that rats with LH lesions defend a reduced level of body weight. The changes in energy expenditure that mitigate weight change in sham-lesioned animals are also present in LH-lesioned rats. In the latter, however, these adjustments serve to stabilize body weight at a lower level.     

Prolonging lateral hypothalamic anorexia by tube-feeding

Male rats sustaining lateral hypothalamic (LH) lesions were anorexic for approximately one week following surgery. They then maintained their body weight at a reduced level (approximately 20% below controls) for the remainder of an 8-week postlesion period of observation. By tube-feeding another group of LH animals, their body weight was held at a control level for the first week postlesion. Following tube-feeding, these animals were anorexic for several weeks while their body weights declined to the same reduced level as that of the LH animals not tube-fed. For both groups of LH animals, achievement of a lowered weight level, rather than a time-dependent recovery process, appeared to underlie the return of food intake to levels sufficient for maintaining body weight. By impeding the loss of body weight, tube-feeding can thus prolong the duration of LH anorexia.     

Food intake and utilization in lateral hypothalamically lesioned rats

The daily food intake of rats with lateral hypothalamic (LH) lesions was monitored in two experiments. Confirming earlier reports, LH-lesioned animals were found to ingest nearly the same amount of food per day as nonlesioned controls even though their body weights remained substantially below those of the controls. In view of this result, an experiment was conducted to compare the efficiency of food utilization of LH-lesioned and control animals at different body weights. First, the daily food intakes of seven LH-lesioned rats and seven nonlesioned controls were determined. The body weights of these animals were then lowered by restricting food intake in four successive weekly periods to 85%, 70%, 55% and 40% of their ad lib level. Finally, all animals were refed for one week at their prerestriction levels of food intake reduced in proportion to the intervening loss in metabolic mass (body weight_kg^0.75). At each level of caloric restriction, the weight losses observed in the LH-lesioned and control animals were equivalent. Likewise, though given only prerestriction amounts (indexed to their reduced metabolic mass), LH-lesioned and nonlesioned animals both gained weight rapidly and at equivalent rates during refeeding. Thus, LH-lesioned animals appear to utilize food in a normal fashion and, as do controls, adapt to weight loss by increasing their efficiency of food utilizazion. In the case of LH-lesioned animals, however, such adjustments occur around a reduced level of maintained body weight, or set-point.     

Increased efficiency of food utilization following weight loss

The efficiency of food utilization following a period of restricted caloric intake was examined under controlled feeding conditions. By restricting caloric intake, the body weight of two groups of rats was reduced to either 92 or 81% of that of an unrestricted control group. For one week, all animals were then fed daily an amount of food equal to their prerestriction intake, adjusted for the intervening change in metabolic mass ($\text{FI}\text{BW}{}_{\mathrm{kg}}{}^{0.75}\text{=}\text{K}$). During this period of realimentation, the control animals gained an average of 1.6 g body weight while ingesting 156.1 g of food. The two restricted groups gained 21.4 g on 154.2 g food and 29.6 g on 140.4 g food, respectively. This inverse relationship between weight gain and food intake provides evidence that underweight animals utilize food more efficiently than do undeprived control animals.     

Effects of two body weight reduction regimens on schedule dependent and schedule induced behavior

Fifteen male hooded rats were divided into three equal groups on the basis of body weights. One group was allowed to eat ad lib and constituted the Control Group. The second group of animals was reduced over 7 days and adjusted to 80 percent of the body weight of the animals in the Control Group for a 23 day period and constituted the Adjusted Group. Animals in the third group were reduced to 80 percent of their own predeprivation body weight over 7 days and were maintained at this constant level for a 23 day period and constituted the Constant Group. The two experimental groups were then allowed to feed ad lib for the remainder of the experiment. Both the Adjusted and the Constant Groups were tested throughout restricted and ad lib eating periods on a FI 1 min food reinforcement generator schedule. Schedule dependent lever pressing, schedule induced licking and drinking, food intake and body weights were recorded for the duration of the experiment. Results demonstrate that schedule induced licking and drinking and schedule dependent lever pressing increased in the Constant Group at reduced body weight. Animals in the Adjusted Group did not change significantly on these measures during the same periods. When animals were returned to ad lib feeding conditions, the Constant Group initially increased body weight at a faster rate, ate significantly more, and exhibited significantly increased schedule induced licking and drinking. These initial differences disappeared later during the same period. The two experimental groups did not attain the expected body weight of the normal Control Group during 78 days of ad lib eating. Apparently, when animals are initially deprived rapidly and maintained at relatively constant body weight reduction, a prolonged body weight deficit occurs even though these same animals eat normal amounts of food.     

Effects of lateral hypothalamic lesions on schedule dependent and schedule induced behavior

Rats were reduced to 80 percent body weight and were exposed to an FI 1 min food reinforcement schedule for 30 min daily until lever presses, licks and water consumption stabilized for at least 10 days. Six animals were subjected to bilateral mid lateral hypothalamic (LH) lesions and 6 animals to bilateral posterior LH lesions. Animals were tested for 50 days following the lesions at 80 percent body weight, were permitted to recover body weight, and were tested for an additional 30 days under ad lib feeding and after body weight recovered. Animals were then subjected to the following four home cage tests: food consumption following food deprivation; drinking following water deprivation; insulin induced eating; and salt arousal of drinking. On the basis of the data collected in these tests and lesion locus and size, the 12 experimental animals were divided into 3 groups--asymmetrical, typical and posterior bilateral LH lesion and were compared to a sham lesion control group of 4 animals. The asymmetrical LH lesion group was similar to the sham lesion group except lever pressing was significantly depressed. Typical bilateral lesion animals displayed the usual LH syndrome with prolonged depression of both schedule dependent lever pressing and schedule induced licking and drinking. Posterior bilateral LH lesions produced the most drastic effects on both schedule dependent and schedule induced behavior. Results indicate that the neural mechanism which is involved in schedule induced polydipsia is destroyed by posterior bilateral LH lesions.     

Area postrema/nucleus of the solitary tract ablations: Analysis of the effects of hypophagia

The effect of hypophagia following lesions of the area postrema and caudal-medial aspect of the nucleus of the solitary tract (AP/cmNTS) on body-weight, water intake and preference for palatable diets was examined. Following AP/cmNTS ablation, rats reduced pelleted-food intake to a degree which was sufficient to account for the weight loss and increased water:food ratios observed. Restricting food intakes of intact rats to levels taken by lesioned animals resulted in similar weight losses and increased water:food ratios. When offered both pelleted food and milk, lesioned rats took more calories as milk than did previously food-restricted intact rats. Thus, the hypophagia of AP/cmNTS lesioned rats does not account for their increased preference for milk diets. Lesioned rats ate less high-fat diet than did intact or sham-lesioned controls and did not increase their intakes when this diet was sweetened. At autopsy, retroperitoneal and epididymal fat-pad weights accounted for less of the total body weight of lesioned animals than controls suggesting that body-fat levels are reduced following AP/cmNTS ablation.     

Lifelong food restriction prevents senile osteopenia and hyperparathyroidism in F344 rats

Studies were carried out on male F344 rats to examine the influence of aging and life-prolonging food restriction on bone and circulating parathyroid hormone levels. In ad libitum fed animals, the weight, density and calcium content of the femur increased with age and achieved their peak levels by 12 months of age. These levels remained stable until about 24 months and by 27 months of age the ad libitum fed animals had lost appreciable amounts of bone. The maturation of the femurs of the animals maintained on 60% of the ad libitum food intake was delayed and their bones were lighter, less dense and contained less calcium than bones from ad libitum fed rats of corresponding ages. But at 6, 12 and 24 months of age, the femur strength to body weight ratios were very highly significantly greater (P < 0.0001) for the restricted animals compared to the ad libitum fed controls. Circulating immunoreactive parathyroid hormone increased progressively with aging in the animals fed ad libitum and the animals that experienced bone loss at advanced age also had the highest level of the hormone. In contrast, in the food restricted animals aging was not associated with a marked increase in serum parathyroid hormone or with senile bone loss. The data are discussed in relation to the mechanism of the observed changes.     

Overcompensation of food intake following brief periods of food restriction

Four adult female Sprague-Dawley rats, maintained on an ad lib feeding schedule were deprived for either 0, 0.5, 1, 2, 4, 6, or 8 hours during the dark phase of the day-night cycle. It was found that the latency to initiate the first meal following the deprivation was independent of the previous deprivation interval. The animals were found to overcompensate for the periods without food by eating a large initial meal that increased proportionately in size with the duration of food restriction. Furthermore, the animals continued to overeat throughout the day. This deprivation-induced overeating by the animals resulted in an overcompensation in total food consumption that was 21–56% greater than on control days. The role of food intake as a regulator of body weight is discussed.     

The control of puberty in the dietary restricted female rat

Food intake, body weight and serum LH, FSH, progesterone and oestradiol-17 beta were monitored from weaning to puberty in fully fed females housed in groups of four or individually and in females individually housed and dietary restricted. Restriction of food intake from weaning delayed the onset of puberty (34-39 days fully fed, 63-189 days dietary restricted) which was achieved at the same body weight as in the fully fed females. Individual housing of fully fed rats resulted in a significant increase in relative and absolute food intake (but not body weight) and a decrease in serum FSH when compared to group housed fully fed animals. Serum FSH and progesterone were significantly decreased in restricted females and serum oestradiol-17 beta significantly increased.     

Self-starvation: A problem of overriding the satiety signal?

Rats housed in either activity wheels or standard laboratory cages received access to food either ad lib or for one 60-min, two 30-min, or four 15-min periods per day. Imposition of restricted feeding schedules led to reductions in food intake and body weight which were greater for animals with access to activity wheels. Increases in activity reflected the percent of body weight loss, which varied directly with frequency of food access. Subsequent recovery of intake was facilitated by partitioning total feeding time into briefer but more frequent periods. In the most extreme frequency-of-access condition, animals with access to running wheels failed to recover from the reduction of intake incurred by imposition of the restricted feeding schedule, even though their total feeding time was the same as that of animals that did recover. These data indicate that self-starvation is not induced by activity per se but results from a general failure to recover intake which, in turn, results from a failure to override the satiety signal within a meal.     

Effect of treadmill exercise on food intake and body weight in lean and obese rats

Body weight and food intake of lean and obese, male and female Osborne-Mendel rats following treadmill exercise were compared. Rats were assigned, separately by sex, to one of three diet groups; Group 1 was fed a low fat (10%) diet throughout the study, Group 2 was fed a high fat (55%) diet for 16 weeks and then switched to the low fat diet 1 week prior to exercise, and Group 3 was fed the high fat diet throughout the study. To control for differences in work output between the leanest and heaviest animals, exercise intensity was adjusted across groups such that all exercised rats had equivalent energy expenditure. After a 3 day training period, the exercise was successively increased over 8 days until a work output of 374.9J was reached. Relative to their respective controls, obese exercised males showed a reduction in body weight but no change in food intake. In contrast, exercised females showed no change in body weight or food intake, regardless of dietary condition.     

Weight loss,slower growth and lower fasting heat production rates following LH lesions in female rats

Lesions in the lateral hypothalamus (LH) can result in a permanent loss of body weight and slower growth in female rats, but do not do so invariably. Weight and growth rate changes were always accompanied by lower rates of fasting heat production (FHP) independent of changes in activity. The thyroids of these animals were significantly below normal in size. None of the traditional deficits of the “LH syndrome” were present: the animals ate when deprived of water: drank when deprived of food (although less than the control animals) and increased their food intakes when injected systemically with insulin, at least on the initial test. With repeated tests the food intake following insulin-induced hypoglycemia declined both in the animals with lesions and in the animals whose body compositions and weights had been lowered to the same levels.     

Involvement of a humoral factor in regulation of body weight in parabiotic rats.

Excessive food intake and obesity was induced in one member of parabiotic pairs by electrical stimulation (three 30-min sessions/day for 2 wk) of the lateral hypothalamus (LH). The nonstimulated partners reduced spontaneous food intake the fatter the stimulated animals became. This reduced food intake resulted in a decreased body weight, fat content, and fat-free solid body mass. The decrease of food intake was not due to changed social behavior of the obese partner. It must be attributed to transmission of a humoral satiety factor. The very first stimulation of the LH in the stimulated partners resulted in a large increase in blood glucose and glucagon level without much change in the insulin level. These changes in blood parameters were probably due to strong sympathetic arousal. In the nonstimulated animals there were practically no changes in these parameters. One week of fattening resulted in increased basal glucose and insulin levels in the stimulated animals and decreased glucose levels in the nonstimulated partners, in which the basal insulin levels remained nearly normal. Basal glucagon levels were the same in both partners and did not differ from the prefattening situation. At that time during stimulation the obese animals showed a large increase in glucose and glucagon levels and a decrease in insulin level. On the other hand the nonstimulated animals showed a slow gradual increase in glucose and insulin level due to transmission from their fat partners because of the large gradient in these substances between the animals. These phenomena were still more pronounced after 2 wk of fattening. It is tentatively concluded that the humoral satiety factor is neither circulating insulin nor glucagon nor one of the major circulating nutrients.     

The weanling rat ventromedial syndrome: males get just as fat as females

Weanling female and male Holtzman rats received bilateral electroytic lesions in the ventromedial hypothalamic nucleus (VMN) at the age of 27 and 26 days, respectively. Sham-operated rats served as controls. The animals were maintained on a synthetic diet (4.2 Cal/g) and tap water ad lib, and body weight, Lee (obesity) Index, tail length and food and water intake were recorded weekly for 6 weeks. The only parameters in which a significant sex difference could be demonstrated were body weight gains and water intake which were greater in the male VMN rats. Female and male VMN rats also utilized food energy for fat deposition, body weight and body length change to the same extent. The data also show that in growing animals, body weight is a poor criterion for the accurate assessment of obesity status and true growth.     

Electroconvulsive shock effects on food and water intake as a function of prior deprivational state

Two experiments, each using approximately 30 male and 30 female hooded rats, examined the effects of electroconvulsive shock (ECS) on water intake as a function of the water deprivation state of the animal and food intake and body weight as a function of food deprivation state. In Experiment 1, half the animals were subjected to water deprivation prior to ECS or sham ECS, and the other half were watered ad lib; in Experiment 2, food deprivation was the pre-ECS manipulation. As predicted, ECS produced a decrease in water intake in the ad lib watered animals but not in the deprived ones. A similar treatment by deprivation interaction was not found for food intake or body weight. In the males, food intake was decreased for one day by the treatment but recovered to a normal level two days following ECS; however, such an effect of ECS on food intake did not occur in the females. Since food and water intake was not differentially affected by ECS and sham ECS in deprived animals, previous cautions regarding ECS effects on motivational states may not be germane to many studies using appetitive conditioning paradigms.     

Reactivity to aversive stimuli as a function of alterations in body weight in normal and gonadectomized female rats

Two studies compared the quinine aversion and shock thresholds of intact and gonadectomized female rats. Using food deprivation to modify body weight, the first study measured the reactivity of gonadectomized and intact rats at the same weight level and compared their behavior to a food deprived, but heavier, gonadectomized group. While maintained at the same weight levels, no differences in either shock thresholds or quinine aversion were found between gonadectomized and intact animals. The heavier gonadectomized group showed decreased reactivity on both measures. The second study manipulated body weight with gonadal hormones. Estrogen and the combination of estrogen and progesterone maintained the body weight of gonadectomized rats at the level of the intact control group. During this period the reactivity of both estrogen injected groups was not different from the control group. Progesterone had no effect on weight gain and the progesterone injected group did not differ in reactivity from an oil injected gonadectomized group. Both the progesterone and oil injected gonadectomized groups were heavier and showed less reactivity to both shock and quinine. These results were interpreted as direct support for previous work suggesting that the effects of alterations in gonadal hormones are mediated by the weight changes attendant on hormone level changes and are not direct effects of gonadal hormones, themselves.     

Dietary self-selection of golden hamsters in response to acute food deprivation and chronic food restriction

Adult male golden hamsters were maintained on either Purine Rat Chow (Chow diet) or a self-selection diet consisting of high-protein chow, pure fat, and pure carbohydrate (Choice diet). In Experiment 1, animals were deprived of food for single periods of up to 48 hr. Animals on the Chow diet did not increase intake at any time after deprivation; animals on the Choice diet selectively increased their consumption of fat-derived calories and increased their total caloric intake during the first 6 hr of refeeding, but not thereafter. The nature of the diet did not influence the rate at which animals regained weight following deprivation. In Experiment 2, hamsters were placed on food-restriction schedules (access to food either for 1 hr/day only or on alternate days only) until they lost 20% of starting body weight. Chow-fed animals demonstrated little or no change in food intake either during or after food restriction. Hamsters on the Choice diet consumed more calories and lost weight more slowly than did chow-fed animals during 1-hr/day feeding; intake of fat-derived calories was elevated during restriction. Choice hamsters increased total caloric intake only towards the end of the alternate-days restriction schedule. Choice hamsters were hyperphagic following both types of food-restriction schedules, but no increased preference for fat-derived calories was observed. Factors influencing food consumption of hamsters in response to deprivation and restriction are discussed.     

Effect of lateral hypothalamic lesion on brown adipose tissue of Zucker lean and obese rats

Acute (10-day) lateral hypothalamic (LH) lesion induced a reduction of food intake in both lean and obese Zucker rats which averaged about 50% over the course of the first 10 days. The aphagia associated with a fall in body weight in both genotypes which was greater than their respective pair-fed controls, indicating a change in energetic efficiency. The reduced level of BAT protein, mitochondria and GDP binding observed in the obese rat was restored after LH lesion, suggesting the reestablishment of a normal sympathetic drive to the tissue. The markedly lower plasma insulin concentration in the LH lesioned obese rat is consistent with a reduction in parasympathetic activity in these animals. Food restriction in the sham lean rat reduced BAT protein content and mitochondrial GDP binding, whereas no such changes were observed in the food restricted obese rat. This demonstrates the insensitivity of the obese rat to dietary signals and may imply that LH lesion restores diet-induced BAT thermogenesis in the obese rat.     

Ovarian influences on food intake and body weight regulation in lactating rats

In the following experiments, an attempt was made to determine the role of the ovary in the control of food intake and body weight regulation during lactation. In the first study, it was found that concentrations of estradiol benzoate effective in suppressing food intake and body weight in nonlactating animals were not effective during lactation. In the second experiment, ovariectomy during lactation was shown not to produce the usual increases in food intake and body weight or change in meal patterns known to occur after ovariectomy in the nonlactating rat. These results suggested that lactating animals behave the as though functionally ovariectomized and that the removal of the ovaries is of no additional consequence. The further observation that animals nursing small litters gained weight considerably more rapidly than animals nursing large litters led to the prediction that these animals would also be more responsive to the suppressive effects of EB. In the third study, EB in concentrations which are not effective in suppressing body weight in animals nursing large litters was found to suppress body weight in mothers with small litters. However, since these animals also showed a decline in milk yield, a number of alternative interpretations of these results were considered. These results, together with data concerning levels of ovarian hormones during gestation and lactation led to the hypothesis that pregnant and lactating animals undergo an elevation in body weight set-point, similar in magnitude and quality to elevations following ovariectomy in the nonlactating animal.