Maternal malnutrition in the rat: Effects on food intake and body weight

The effects of dietary protein level on food intake and body weight were examined in adult female rats during a 35-day pre-mating period and during gestation and lactation. During the pre-mating period, no differences in daily food intake were observed among rats fed a 6% casein, 8% casein or 25% casein diet. However, during this period, rats fed the 6% casein diet gained significantly less weight than those with ad lib access to the 8% or 25% casein diets or than rats pair-fed the 25% casein diet in amounts equivalent to that consumed by rats in the 6% or 8% casein groups. Additionally, rats fed the 6% casein diet displayed decreased efficiency of energy utilization, calculated as weight gain per 100 kilocalories consumed, relative to rats fed the 8% or 25% casein diets. No differences in food intake were observed among the groups during gestation. However, rats fed the 6% casein diet gained less weight than rats fed the 8% or 25% casein diets. During lactation rats fed either the 6% or 8% casein diet consumed significantly less food than animals given the 25% casein diet ad lib. During the second week of lactation, rats receiving ad lib access to the 25% casein diet gained weight while those receiving the 6% or 8% casein diets continued to lose weight. At parturition, body weights of pups did not differ as a function of dietary condition. However, by day 12 of life, pups whose dams had ad lib access to the 25% casein diet weighed significantly more than pups whose dams consumed the 6% or 8% casein diet or whose dams were pair-fed the 25% casein diet in amounts equivalent to those consumed by rats fed the 6% or 8% casein diet.     

Effects of food restriction and adrenalectomy in rats with VMH or PVH lesions

The effects of adrenalectomy in rats with ventromedial or paraventricular hypothalamic lesions have been studied in two experiments. Rats with ventromedial hypothalamic lesions or lesions in the paraventricular nucleus were allowed to gain weight for fourteen days at which time they were adrenalectomized. Before adrenalectomy, animals with VMH lesions ate more, gained significantly more weight than animals with lesions in the paraventricular nucleus, and both were significantly heavier and consumed more food than sham-operated controls. Following adrenalectomy, food intake decreased and both groups of lesioned animals lost weight. The animals with VMH lesions stabilized at weights above the control animals. Implantation of corticosterone enhanced weight gain and food intake in animals with lesions in either the paraventricular nucleus or the ventromedial hypothalamus. In the second experiment, one subgroup of rats with VMH lesions was adrenalectomized, and allowed to eat ad lib. Two other groups of sham-operated rats with VMH lesions served as controls. One group ate ad lib and one group was pair fed to the food intake of the adrenalectomized VMH-lesioned rats. Weight gain in the adrenalectomized VMH-lesioned rats and the pair-fed VMH-lesioned controls was similar and less than the VMH-lesioned rats eating ad lib. GDP binding to interscapular brown adipose tissue was related to the degree of weight gain, not to the presence of the VMH lesion. These data show that corticosterone is essential for the expression of obesity in both PVH- and VMH-lesioned rats. They also argue that the reduction in the activity of the sympathetic nervous system of VMH-lesioned rats as estimated by the GDP binding to mitochondria from brown adipose tissue is associated with hyperphagia.     

Photoperiodic regulation of body mass and fat reserves in the meadow vole

Short photoperiods reduce both body mass and food intake of male meadow voles. To help determine whether the primary effect of short day lengths is on regulation of some component of body mass or on the control of food consumption, voles housed in a long photoperiod were provided rations equivalent to those consumed by animals in short day lengths. Animals were transferred to a short photoperiod and after either 3 or 6 weeks of food restriction were fed ad lib. Both groups of voles overate after termination of food restriction and achieved seasonally appropriate body masses that were influenced by the duration of short photoperiod treatment. We conclude that short photoperiods gradually alter the regulated level of one or more components of body mass. We tested and failed to support the hypothesis that the subcutaneous fat depot is selectively spared during seasonal weight loss and thereby increases surface insulation. Thus, the proportion of adipose tissue reduction did not differ significantly among the epididymal, retroperitoneal, and inguinal-subcutaneous fat depots of voles housed in short day lengths.     

Relationship between plasma corticosterone and insulin levels in rats with ventromedial hypothalamic lesions

The effects of ventromedial hypothalamic (VMH) lesions on plasma corticosterone, insulin, and glucose levels were studied in food-restricted and ad lib fed female rats. VMH lesions resulted in significant elevations of corticosterone and insulin levels compared to control values during the first 25 days after surgery. However, unlike insulin values which were generally greater in VMH rats fed ad lib than in food-restricted animals, plasma corticosterone levels were unaffected by level of food intake. Corticosterone and insulin levels were unrelated preoperatively and in sham-operated animals, but were positively correlated (r = .82) by Day 25 in ad lib fed VMH rats. It is concluded that the elevation in plasma glucocorticoids observed in VMH rats is a primary effect of the lesion that is independent of food intake or initial weight gain.     

Hypothalamic hyperphagia despite imposed diurnal or nocturnal feeding and drinking rhythms.

Rats normally do most of their eating at night. When ad lib fed rats are made hyperphagic with lesions or parasagittal hypothalamic knife cuts the increases in eating occur primarily during the day. This suggests that a disruption of circadian rhythms may mediate the overeating. However, when knife cut rats were food and water deprived all day excessive eating occurred at night. Similarly, when they were deprived all night overeating occurred during the day. Under both conditions od deprivation the food intakes and rapid weight gains of the ad lib fed knife cut group were defended. It was concluded that: (1) in hypothalamic hyperphagia either the excessive food intake or the excessive weight gain is defended when food and water are available only half of each day, and (2) disruption of nocturnal feeding and drinking rhythms is not the cause of hypothalamic hyperhagia.     

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.     

Hyperinsulinemia in rats with ventromedial hypothalamic lesions: role of hyperphagia

The relation of hyperinsulinemia to hyperphagia was examined in rats with lesions of the ventromedial hypothalamus (VMH). Plasma insulin and glucose levels were assayed after a 4-hr fast and 17 min after the initiation of a meal (6 ml of sweetened milk in 7 min) in animals with sham lesions, VMH animals maintained at preoperative body weight by food restriction, and VMH animals fed ad lib. Both VMH groups displayed basal and postabsorptive hyperinsulinemia, compared with the sham-operated control group, but insulin levels were greatest under the ad lib feeding condition. It is suggested that VMH hyperinsulinemia is due both to a primary effect of the lesion and to hyperphagia and that marked obesity can result in the absence of basal hyperinsulinemia as a result of hyperphagia with consequent postabsorptive hyperinsulinemia.     

Body weight regulation in ground squirrels and hypothalamically lesioned rats: slow and sudden set point changes

Golden-mantled ground squirrels. Citellus lateralis, have a near annual cycle in body weight. In the present experiments their weights were temporarily forced off the usual levels either by food deprivation during a phase of weight gain or by offering extra palatable food during a phase of weight loss. When these treatments ceased the weights returned to levels appropriate for that time of year rather than to pretreatment values. Therefore the cycle of body weight in uniform and ad lib conditions reflects an underlying cycle in slowly climbing or sliding set points for body weight. In contrast to fattening ground squirrels, lesioned rats in the dynamic phase of hypothalamic hyperphagia did not compensate well for weight losses incurred during food deprivation. Weight gain during the dynamic phase appears to be roughly proportional to the discrepancy between actual and set weights, the latter being suddenly much elevated by the lesion.     

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.     

Efficiency of food utilization during body weight gain in dormice (Glis glis)

During spontaneous body weight gain in dormice, Glis glis, progressive increases in the efficiency of food utilization as defined by weight gain (g)/food intake (g), and parallel increases in mean daily food intake were observed. Towards the end of the weight gain period, there was an abrupt drop in feeding efficiency with no significant change in food intake even when the latter was expressed relative to an index of each animal's “metabolic mass” (body weight_kg^0.62). Animals whose body weight increases followed a return to ad lib feeding after prolonged food restriction showed marked decreases in feeding efficiency from initially high values which were independent of changes in food intake. These results are discussed in relation to the sliding set point concept of body weight regulation in hibernators.     

Lack of diet-induced thermogenesis following lesions of paraventricular nucleus in rats

The effects of electrolytic lesions in the hypothalamus paraventricular nucleus were studied in adult male and female Sprague-Dawley rats, fed different diets, consisting of either palatable human food plus chow (cafeteria diet) or chow alone. The results showed that both cafeteria diet and lesions induced an increase in energy intake and weight gain in rats of both sexes. Oxygen consumption rate and colonic temperature were significantly decreased by lesions, while cafeteria diet increased the same parameters only in intact animals. The lesion decreased weight, protein and DNA, and temperature of brown adipose tissue, while cafeteria diet increased the values considered in brown adipose tissue of sham-injured rats, but not in lesioned animals. The response to norepinephrine administration was significantly greater in intact rats and those fed cafeteria diet. The results suggest that the larger body weight gain observed in lesioned rats, particularly evident in rats fed cafeteria diet, is partly due to the disappearance of diet-induced thermogenesis that depends on the reduced mass and functional activity of brown adipose tissue.     

Effects of subdiaphragmatic vagotomy on schedule induced drinking and schedule dependent lever pressing

Fourteen male albino rats reduced in body weight were exposed to a daily 1 hr FI-1 min schedule of food reinforcement. When schedule induced licking and drinking and schedule dependent lever pressing stabilized, seven animals were subjected to bilateral subdiaphragmatic vagus nerve transections and the other seven animals were subjected to sham operations. Changes in licking, drinking, and lever pressing were assessed when animals were reduced to 80% of their initial body weight by partial food deprivation and when body weights recovered after the animals were returned to conditions of ad lib feeding. Results indicate that vagotomy produces a significant decrease in schedule induced licking and drinking when animals are at reduced body weight. When vagotomized rats are allowed to recover body weight due to ad lib feeding, lever presses decrease but licking and drinking are not further reduced. The sham operation had no appreciable effects at reduced body weight. When allowed to recover body weight sham animals exhibited significant decreases in licking, drinking, and lever pressing. In addition, the rate of body weight gain and home cage food and water consumption and water consumed in response to hypertonic saline injections were reduced in vagotomized animals when allowed to feed ad lib. Results are discussed in terms of vagal afferent activity from the viscera to the lateral hypothalamus associated with food deprivation and body weight reduction and the maintenance of adjunctive behavior.     

The effects of restricted food access upon locomotor activity in rats with suprachiasmatic nucleus lesions

The purpose of the study was to investigate the ability of rats with suprachiasmatic nucleus (SCN) lesions to anticipate restricted food access (RFA). The sham operated controls demonstrated entrainment of locomotor activity to a LD 12:12 cycle with ad libitum food and water, while the lesioned animals were arrhythmic in their running behavior. When exposed to constant light (LL) and presentation of food once every 24 hours, anticipatory wheel running was observed in both groups. A return to ad lib food and the previous LD 12:12 schedule produced a slow re-entrainment of running in the controls and arrhythmic activity in the SCN animals. The results suggest that the SCN is not necessary for the appearance of locomotor rhythms in the rat.     

Food availability and photoperiod affect reproductive development and maintenance in the marsh rice rat (Oryzomys palustris)

To examine whether photoperiod and food availability interact to influence reproductive development (Experiment 1), we exposed juvenile male and female rice rats to 16L:8D or 14L:10D and to ad lib, 80% of ad lib, or 60% of ad lib food intake from 3 to 8 weeks of age and recorded body and reproductive organ masses. Absolute paired testis masses were similar in ad lib and 80% of ad lib groups but significantly different than the 60% of ad lib group in both photoperiods. Relative paired testis masses were significantly different in the 80% and 60% of ad lib groups on 16L:8D only. Absolute seminal vesicle masses (SVM) were directly dependent upon the level of food restriction in both photoperiods, but relative SVMs were different only in the 60% of ad lib group. Terminal body masses were also directly dependent upon the level of food restriction and were greater on 16L:8D than on 14L:10D at most levels of food availability. In juvenile females, absolute uterine mass was only affected in the 60% of ad lib group on 14L:10D, while absolute paired ovary masses were affected on both photoperiods in the 60% of ad lib groups only. There was no effect of photoperiod or food on relative uterine and paired ovary masses. Terminal body mass was affected by food intake in both photoperiods. Lastly, in adult males (Experiment 2), photoperiod and food restriction affected reproductive function. Within a photoperiod, there was no effect of food restriction (75% of ad lib) on the testes, seminal vesicles, or testosterone levels in animals housed on 16L:8D, but terminal body mass was significantly reduced. On 12L:12D, however, food restriction significantly decreased testes and SVMs relative to ad lib-fed controls. Testosterone levels were reduced regardless of food availability. There was no effect of food restriction on terminal body mass. These results suggest that multiple potential environmental cues can be utilized to affect gonadal status in both juvenile and adult marsh rice rats.     

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.     

Weight cycling in female rats increases dietary fat selection and adiposity

The effect of repeated food restriction-refeeding (weight cycling) on macronutrient selection and adiposity was investigated in female Sprague-Dawley rats. Rats were maintained on ad lib macronutrient self-selection and were put on one of two types of restriction. One group was reduced to 75% of their body weight on restricted amounts of chow and a second group was given ad lib chow during the concurrent period and were voluntarily hypophagic. During refeeding on macronutrient self-selection, animals previously restricted selected a higher percentage of dietary fat, had larger adipose depots and plasma insulin values, and had lower heart weights both expressed in grams and as a percentage of body weight than non-restricted groups. This suggests that both severe and moderate periods of restriction may have negative health consequences.     

The effect of dorsomedial hypothalamic nuclei lesions on body weight regulation.

Prior to hypothalamic surgery 1 group of male rats was placed on a partial starvation regimen to lower their body weight. A second group was fed ad libitum. Just before surgery the 2 groups were divided into 2 sub groups. Bilateral electrolytic lesions were then placed in the dorsomedial hypothalamic nucleus in some of the partially starved and some of the ad libitum fed rats. The remaining animals were sham operated. After surgery all groups were fed ad libitum. Following hypothalamic operation the group that before surgery had been fed ad libitum showed the previously reported postoperative hypophagia and reduced body weight. On the other hand, the rats that were partially starved prior to placement of the lesion, ate significantly more than ad libitum fed lesioned animals during the first 9 days after surgery. The body weights of the partially starved, lesioned rats increased steadily from the day of the operation while lesioned rats fed ad libitum showed an initial delay of ponderal growth. The data suggest that the transient postoperative increase in food intake of the partially starved, lesioned rats is an active process to bring the body weight of these animals up to a new but lowered ‘body weight set point’ initiated by the hypothalamic destruction. Since previous studies had shown that rats with a lesion in the dorsomedial nucleus have a normal body composition, it is suggested that the lesions change the animals' ‘body weight set point’ and not the ‘body fat set point’, as has been suggested after ventromedial and lateral hypothalamic lesions.     

Defense of a lowered weight maintenance level by lateral hypothamically lesioned rats: Evidence from a restriction-refeeding regimen

Male rats maintained their body weight at approximately 85% that of sham-lesioned controls following lesions of the lateral hypothalamus (LH). One month following surgery, the food intake of half the LH-lesioned animals was restricted until their body weight had declined to 80% that of nonrestricted LH animals. Half the sham-lesioned animals were similarly restricted until their body weight fell to 80% that of nonrestricted control animals. When returned to an ad lib feeding schedule, both restricted groups were initially hyperphagic and quickly restored their body weights to the level of the nonrestricted group from which they were originally selected. In doing so, the LH animals increased their food intake by the same amount and took the same number of days to restore their weight to control levels as the sham-lesioned animals. These observations provide further evidence of the vigor and effectiveness with which LH animals defend their reduced level of maintained body weight.     

Anorexia, food deprivation and hibernation

Two experiments examined the relationship between food eaten and the lenghts of bouts of continuous hibernation of golden-mantled ground squirrels, Citellus lateralis, kept at 5 ± 4°C. The first experiment showed that food deprivation at the start of the hibernation season increased the hibernation bout lengths compared to a control group given food ad lib. The second experiment showed that animals without food at the end of the hibernating season decreased bout lengths to near to 4 days; they continued to hibernated in this manner until refed at which time hibernation soon stopped altogether. Factors other than food intake contributed toward determining bout lengths since progressive changes in durations of continuous hibernation occurred at different times of year even in food deprived animals. It was argued that if high food intakes are incompatible with staying in a torpid state for many days on end, then set points for body weight must necessarily be lowered over the hibernation season.     

Refeeding after differential severity of deprivation

Forty-eight female rats were randomly assigned in equal numbers to an eight-day 0, 20, 23, 23.5, 46-hour food deprivation schedule, or complete starvation, followed by two weeks of ad lib refeeding. Two of the completely starved subjects died. Due to decreased metabolic need of the animals after weight loss, daily food intake was considered relative to body weight. Water consumption relative to body weight increased by the end of deprivation except for animals unadapted to deprivation. The major findings during refeeding were: (a) post-starvation anorexia does not occur after any form of starvation (scheduled or complete) when body weight is considered; (b) instead of being highest on the first day of refeeding, food consumption slowly increases to a maximum and then returns to ad lib control level; (c) the more severe the deprivation, the longer time for food consumption to reach its maximum and return to control levels; (d) the more severe the deprivation, the greater the maximal food consumption.