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.     

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.     

Effect of skeleton photoperiod and food availability on the circadian pattern of feeding and drinking in rats

Feeding and drinking behavior were measured in rats maintained under a 12:12 light-dark (LD) cycle or skeleton photoperiod (SPP). Feeding and drinking were closely associated during the normal LD cycle but under SPP conditions an increased feeding activity during the subjective day was not accompanied by an equivalent increment of water intake. This indicates a stronger coupling of drinking to the subjective night. A restriction of food availability to the subjective light phase did not cause an accompanying complete shift in drinking behavior. These results suggest that drinking is largely dependent on the influence of a circadian oscillator and this association is not disrupted by changes in feeding schedule. A change in food access to the subjective light phase caused partial but not permanent desynchronization between feeding and drinking behavior. Synchrony was reestablished within one day once food was available ad lib. Complete return to the original feeding and drinking patterning took 3 days. It is suggested that separate slave oscillators controlling feeding and drinking are governed by a hypothesized "master" circadian oscillator which remains definitely entrained to the original rhythm by the light pulses of the SPP condition.     

Hoarding of food and non-food items in blind, anosmic and intact albino rats

Hoarding was studied in anosmic, blind, and sham-operated rats. It was found that: (1) blindness had little effect on hoarding, while anosmia led to increased hoarding in both ad lib and food-deprived conditions; (2) during ad lib feeding, blind and sham-operated animals showed a preference for wooden blocks over food pellets. During deprivation the reverse occurred. The anosmic animals did not display any consistent preference during ad lib feeding, but behaved like the other groups during deprivation; and (3) anosmic rats showed an initial increase in both latency to emerge from the home cage and time spent in the cage. It is concluded that (1) neither olfactory nor visual cues are necessary to elicit any of the behaviors which are involved in hoarding; (2) the increased hoarding of anosmic rats may be related to increased shyness; and (3) the preference for wooden blocks over food pellets during ad lib feeding may be related to gnawing.     

Effects on growth and endocrine status of maintaining obese and lean Zucker rats at 22 degrees C and 30 degrees C from weaning

Lean and genetically obese Zucker rats were maintained from 21 to 34 days of age at an ambient temperature of 22 degrees C or 30 degrees C. Maintenance at 30 degrees C normalised the lower rectal temperature of obese rats. At 30 degrees C obese rats reduced their food intake compared with obese animals at 22 degrees C but they were still hyperphagic compared with non-obese animals at 30 degrees C. At 30 degrees C obese rats accumulated as much lipid in their carcase, but deposited less protein than obese animals at 22 degrees C. Obese rats were hyperinsulinemic compared with non-obese animals at either temperature. Plasma T3 and T4 levels did not differ between phenotypes and T4 levels were lower in both phenotypes at 30 degrees C. Plasma corticosterone levels were higher in obese rats at both temperatures and this phenotypic difference was larger at 30 degrees C. In a second experiment rats were maintained at 22 degrees C from 21-34 days of age and obese rats pair-fed to the ad lib intake of non-obese animals. Obese rats still became more obese than non-obese animals and deposited less protein than either non-obese or ad lib fed obese animals. Pair-fed obese rats were hyperinsulinemic and had higher plasma corticosterone concentrations than non-obese animals. These findings suggest that the raised plasma corticosterone concentrations of obese rats kept at 30 degrees C, or not allowed to express their greater appetite, may cause reduced protein deposition.     

Effect of insulin in rats with lesions of the dorsomedial hypothalamic nucleus.

Four hours after insulin injection Dorsomedial Hypothalamic Nuclei (DMN) lesioned rats consumed an amount of food that was comparable to that eaten by injected sham-operated animals. However, the DMN lesioned rats are not as initially responsive to the food intake stimulating properties of insulin as are the controls. A second study showed ad lib fed and fasted lesioned animals displayed a lower plasma glucose concentration after insulin challenge than did respectively treated controls. This suggests the initial insulin-induced feeding of the lesioned rats was blunted when compared to the controls even in the face of lower plasma glucose levels. Although a previous investigation revealed that DMN lesions destroy glucoreceptor tissue, the present data shows that DMN lesioned rats will increase their food intake in the face of insulin challenge, albeit their initial feeding response to insulin challenge is somewhat blunted. Finally, the present study confirms a previous report in that DMN lesioned rats can competently meter their 24 hour calorie intake.     

Effects of feeding a single daily meal and of changes in lighting schedule on the circadian rhythms of oxidoreductases in the rat gastric mucosa.

The present paper investigated the effect of restricted feeding (11.00 to 13.00 h) by a single daily meal upon the activity of various oxidoreductases of the rat gastric mucosa (SDH, alpha-GPDH, LDH, NADHTR), which at ad libitum feeding under normal lighting conditions with a dark night were shown to have distinct circadian activity variations related to the rat's nocturnal food intake preference (Zaviacic and Brozman 1978a). 1st part of the animals received food in 2-h-period by natural daylight (natural lighting conditions), the 2nd part at the same period of time but in the dark (lighting conditions reversed to natural). Checking the consumption of food, we found the animals to become adapted to the new time of food intake beginning with the 6th experimental day. The circadian rhythm of enzymes was examined on days 69, 83, 97, and 104 of limited feeding under the defined lighting schedule, at 06.00 h, 12.00 h, 18.00 h, and 24.00 h in groups of 5 animals. Synchronization of the highest dehydrogenases activities (particularly of SDH) with the time of restricted feeding was seen to develop in the gastric mucosa of the rat. The synchronization effect was more pronounced in the animals which received their food in the dark (and here even more in male than in female). The effect of light during food intake was found to be rather interfering with the development of synchronization of dehydrogenase activities with the time of food intake, and the influence was again more marked in male than in female. The time of food intake was at the feeding schedule restricted to daytime intake the main synchronizer for the circadian rhythm of oxidoreductases of the gastric mucosa of the rat, with the highest daily activities recorded around the feeding time and the lowest activities at night, which is the direct opposite of the circadian rhythm of the same enzymes determined in rats fed ad libitum under normal lighting conditions with a dark night.     

Circadian patterning of feeding,drinking and activity during diurnal food access in rats

Using an “ecologically” relevant approach, the present study investigated (1) the association between feeding and drinking patterns and their circadian organization and (2) changes in general activity (or life-style), during ad lib conditions (fa:LD) and in a situation where access to food was restricted to the light phase (fa:L). Rats were housed in large outcages with nest boxes. Feeding, drinking, activity, outcage and nest occupation were recorded automatically throughout the day-night cycle. Access to food was restricted by a sliding door situated in front of the food hopper. Under ad lib conditions rats were mainly nocturnal, eating 94% and drinking 95% of their daily intakes at night. The patterns of food and water intake were similar, showing a bimodal distribution over the dark phase. During fa:L rats showed an initial large peak in feeding with lights on, followed by a long pause. Thereafter, feeding activity was variable but remained at a low level. The nocturnal drinking pattern persisted. However, 17.5% of daily water intake was meal-associated, compared with 71% during ad lib. Diurnal activity was associated with feeding and nocturnal activity with drinking. Nocturnal outcage and nest occupation patterns were not shifted to the light phase. The experiment demonstrates that rats on an fa:L schedule reduce food and water intake, and body weight, while still retaining circadian characteristics in the temporal distribution of drinking, activity, outcage and nest occupation. Further, although feeding and drinking may be causally related they need not occur in close temporal association. The rapidity of re-establishment of the normal feeding pattern, on return to free-feeding, and the close association with drinking under normal conditions, suggest the existence of a single or two coupled oscillators controlling feeding and drinking.     

Maternal deprivation in neonatal rats alters the expression of circadian system under light-dark cycles and restricted daily feeding in adulthood

Effects of maternal deprivation (MD) with different conditions were examined on the circadian rhythms in plasma corticosterone and locomotor activity in adult rats under ad libitum and restricted daily feeding (RF), in which rats had free access to food for 2 h for 3 weeks. Three different types of MD were performed from postnatal day 1 (P1) to day 6 (P6); MD for 12 h/day (MD12), for 3 h/day in the morning (MD3am) and in the afternoon (MD3pm). Under ad libitum feeding, corticosterone levels at 08:00 h and 24:00 h were significantly increased in MD12 rats. A similar increase was detected in MD3am rats, but not in MD3pm rats. Under the RF, corticosterone levels at 08:00 h, 24:00 h, and 04:00 h were significantly increased in MD12 rats. Similar elevations were detected in MD3am rats, but not in MD3pm rats. Furthermore, prefeeding locomotor activities under the RF increased significantly in MD12 rats. A similar increase was observed in MD3am rats, but not in MD3pm rats. Keeping ambient temperature and humidity at 37 degrees C and 70-80% during MD attenuated the effects of MD on the corticosterone rhythmicities under RF as well as ad lib feeding. It is concluded that MD in the early postnatal period influences the expressions of circadian rhythms in plasma corticosterone and locomotor activity in adult rats. Not only the length but also the time of day of MD seems to be critical for these effects. Ambient temperature and/or humidity are suggested to be one of the factors by which MD exerts its effect.     

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.     

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.     

Effects of fasting on plasma catecholamine, corticosterone and glucose concentrations under basal and stress conditions in individual rats

Plasma noradrenaline (NA), adrenaline (A), corticosterone (CS) and glucose concentrations were determined in blood sampled via a cardiac catheter from freely moving male rats under ad lib fed and 24 hr food deprived conditions using a repeated measures within-subject design. Resting plasma NA and glucose levels were lower in the fasted condition as compared to the fed situation. One day of refeeding reinstated the decreased NA and glucose values to prefasting level. Exposing 24 hr food deprived animals to the psychological stress of a novel environment resulted in larger NA and glucose increases, an unchanged A release and a lower CS rise in comparison with the responses during the free feeding state. The results show the usefulness of a within-subject design to detect subtle changes in plasma NA contents. Additionally, the data support the concept of selective control of the sympathetic nervous system and adrenal medullae. It is argued that hypothalamic noradrenergic mechanisms may be linked to the fasting-induced effects on the sympatho-adrenal system.     

Nutritional considerations in the production of rodents for aging studies

Dietary restriction in the maintenance of animals for aging research has been the subject of intense recent interest. This interest may be justified. Current formulas for laboratory animal diets were a natural progression from those for farm animals, but the objectives and conditions for maintaining laboratory and farm animals are often quite different. Indeed, the practice of ad lib feeding current laboratory animal formulations may actually have deleterious effects that can be reduced or eliminated by restricting food intake. This paper reviews many of the major considerations in the development and application of dietary restriction protocols, including formulation, nutritional management during long-term studies, and practical considerations.     

Food ingestion is more important to plasma corticosterone dynamics than water intake in rats under restricted daily feeding

The roles of food and/or water ingestion in the regulation of plasma corticosterone level were examined in rats under restricted daily feeding. When the time of food-pellets and water supply was restricted to 2 hours in the early light period (meal feeding) for 2 weeks, the corticosterone level increased prior to meal (prefeeding peak). A similar prefeeding hormone peak was observed when supply of food-pellets was restricted to 2 hours with free-access to water (food restriction). In contrast, when water supply was restricted to 2 hours with free-access to food-pellets (water restriction), the hormone level before water supply did not increase as much as that under meal feeding or food restriction. Shortening of an available time for water under water restriction or prolongation of the restriction schedule failed to elevate the hormone level furthermore. On the other hand, the high prefeeding corticosterone level before meal decreased subsequently to meal feeding (prandial fall), which was not observed when rats were kept fasting during the meal time. This prandial fall of the hormone level was not observed by water intake alone, and closely related to food-pellets ingestion. It is concluded that food ingestion is more important than water intake to the formation of the prefeeding corticosterone peak and to the prandial fall of the hormone level under restricted daily feeding.     

Effects of food restriction on glucose tolerance, insulin secretion, and islet-cell proliferation in pregnant rats

Pregnancy is associated with increased glucose-stimulated insulin secretion and increased pancreatic islet-cell proliferation. In the present study it was investigated whether increased food intake, as occurs during pregnancy, is involved in the regulation of these phenomena. From Day 0 of pregnancy, rats received each day the mean amount of food they consumed daily during the estrous cycle prior to conception. This food restriction regime resulted in lower maternal body weight, and in lower fetal weight on Day 20 of gestation, but did not affect fetal survival. Food-restricted rats showed decreased insulin responses to an i.v. glucose challenge on Day 13, and lower islet-cell replication rates on Day 14 of pregnancy than pregnant rats fed ad lib. Plasma lactogenic activity in food-restricted animals was increased on Days 11 and 13; plasma progesterone levels were unchanged, but plasma leptin concentrations declined progressively during food restriction. Glucose tolerance was normal, suggesting that food restriction improved insulin action. On Day 20 of pregnancy, insulin responses were similar in food restricted and ad lib-fed rats; glucose tolerance was still unchanged. It thus seems that the improved insulin action as present on Day 13 had disappeared on Day 20. Also on Day 20, lactogenic activity as well as progesterone concentrations were similar in food-restricted and ad lib-fed rats. It was concluded that increased food intake plays an important role in the stimulation of islet-cell proliferation and insulin secretion, as well as in the diminished insulin action during the second week of rat pregnancy.     

Effects of restricted daily feeding on freerunning circadian rhythms in rats

Male rats were kept in conditions of constant dim illumination and alternately fed ad lib or for 2 or 4 hr per day only. Locomotor activity was recorded as wheel running and as activity in the cage by a microphone system. At selected days before, during and after restricted feeding (RF) blood samples were taken from the tail in 4-hr intervals for the determination of plasma corticosterone. Under both schedules of RF, the circadian rhythms of activity and of plasma corticosterone continued to freerun without significant changes in period or phase while the feeding times were anticipated by increases in activity and in plasma corticosterone. After the termination of RF, the anticipatory components persisted for several days and merged into the freerunning rhythms through transients. The results support the concept of two systems with oscillatory capacities: the freerunning system which is driven by a pacemaker and not affected by RF, and the anticipatory system which can be uncoupled from the freerunning system by an entraining feeding cycle.     

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.     

Somatic, metabolic and endocrine correlates of set point recovery in food-restricted and ad lib-fed weanling rats with dorsomedial hypothalamic lesions

Male Sprague-Dawley rats received either electrolytic lesions in the dorsomedial hypothalamic nuclei (DMNL rats) or sham-operations (CON), and were fed lab chow ad lib for 41 post-operative (POP) days. Subsequently one lesioned (DNML-AL) and one control group (CON-AL) continued to receive lab chow ad lib until the end of the experiment (POP day 78). A second lesioned (DMNL-RE) and control group (CON-RE) were given 80% of the amount of food eaten by their ad lib-fed counterparts for 28 days. At this time several rats from each group were killed. The remaining animals were then given lab chow ad lib for nine days and then also killed. Both DMNL-RE and CON-RE recovered their lowered body weight, food intake and feeding efficiency and showed the same pattern and relative magnitude as their ad lib-fed counterparts. Similarly, carcass lipid, epididymal fat pad lipid, incorporation of glucose-U-C14 into fat pad saponifiable lipid, total lipid, total glycogen (DPM/protein), liver protein, incorporation of glucose into liver CO2 and concentrations of plasma glucose, glycerol, triglycerides and free fatty acids normalized on refeeding to the same extent and in the same pattern in DMNL-RE as in CON-RE. In contrast to previous studies, plasma insulin was lower in DMNL-AL than in CON-AL but DMNL-RE and CON-RE had similar levels on refeeding. Also on refeeding, both DMNL-RE and CON-RE showed the same enhanced glucose incorporation into liver total lipid. The data show that DMNL rats, although smaller in size and hypophagic in absolute terms, recovered lost body weight--at least under our relative mild reduction of 80% of their ad lib-fed controls--with the same competence and in the same time interval as sham-operated controls. It is quite possible that a more severe restriction of body weight would have uncovered some deficits in DMNL rats, however. Under the constraints of the present experimental arrangement, the data strengthen previous evidence for the existence in DMNL rats of an "organismic" set point that makes for a "scaled-down" but homeostatically normal animal.     

Meal patterning of rats with changes in day length and food availability

Feeding activity in rats is mainly nocturnal, with about 70–90% of the total daily intake eaten in the dark phase. During this phase, feeding has a typical biomodal pattern, i.e. a high level of feeding activity early and late in the night. The aim of the present study was to investigate the effects of temporary food restriction at dawn and dusk, and advanced light onset on the bimodal feeding pattern of male rats. It was found that suppression of food intake by restricting access to food or altering light onset act in radically different ways on the circadian meal patterning. It is argued that food restriction led to a general metabolic deficit, which was compensated by an increase in intake, especially after deprivation. Advancing light onset shifted the “dawn peak” of food intake to precede light onset. The results suggest that under these experimental conditions advancing light onset but not temporary food restriction can “reset” the circadian pacemaker.     

Increased drinking of a nonpreferred NaCl solution during food deprivation in the C3H-HeJ mouse

When food was given ad lib, C3H/HeJ mice showed a progressive decrease in NaCl solution intake as the concentration increased from 0.5–2.5% under single tube or double tube conditions. Under the latter condition, 1.5% NaCl intake volumes were approximately 20% of water intake volumes. However, when restricted to $\text{1}\text{3}$ normal food intake, the mice showed significant increase in the intake of 1.5% NaCl and several animals consumed more salt solution than water. Salt intakes declined to predeprivation levels upon return to free feeding. Since feeding of a sodium deficient diet produced no alteration in intake of 1.5% NaCl, the increase during food deprivation was attributed to hypovolemia rather than hyponatremia.