Amylin blunts hyperphagia and reduces weight and fat gain during recovery in socially stressed rats

During recovery from social stress in a visible burrow system (VBS), during which a dominance hierarchy is formed among the males, rats display hyperphagia and gain weight preferentially as visceral adipose tissue. By proportionally increasing visceral adiposity, social stress may contribute to the establishment of metabolic disorder. Amylin was administered to rats fed ad libitum during recovery from VBS stress in an attempt to prevent hyperphagia and the resultant gain in body weight and fat mass. Amylin treatment reduced food intake, weight gain, and accumulation of fat mass in male burrow rats, but not in male controls that spent time housed with a single female rather than in the VBS. Amylin did not alter neuropeptide Y (NPY), agouti-related peptide (AgRP), or proopiomelanocortin (POMC) mRNA expression in the arcuate nucleus of the hypothalamus as measured at the end of the recovery period, nor did it affect plasma corticosterone or leptin. Amylin exerted most of its effect on food intake during the first few days of recovery, possibly through antagonism of NPY and/or increasing leptin sensitivity. The potential for chronic social stress to contribute to metabolic disorder is diminished by amylin treatment, though the neuroendocrine mechanisms behind this effect remain elusive.     

Interaction of Leptin and Amylin in the Long‐term Maintenance of Weight Loss in Diet‐induced Obese Rats

We have previously shown that combined amylin + leptin agonism elicits synergistic weight loss in diet‐induced obese (DIO) rats. Here, we assessed the comparative efficacy of amylin, leptin, or amylin + leptin in the maintenance of amylin + leptin–mediated weight loss. DIO rats pretreated with the combination of rat amylin (50 µg/kg/day) and murine leptin (125 µg/kg/day) for 4 weeks were subsequently infused with either vehicle, amylin, leptin, or amylin + leptin for an additional 4 weeks. Food intake, body weight, body composition, plasma parameters, and the expression of key metabolic genes in liver and white adipose tissue (WAT) were assessed. Amylin + leptin treatment (weeks 0–4) reduced body weight to 87.5% of baseline. Rats subsequently maintained on vehicle or leptin regained all weight (to 104.2 and 101.2% of baseline, respectively), those maintained on amylin had partial weight regain (97.0%). By contrast, weight loss was largely maintained with continued amylin + leptin treatment (91.4%), associated with a 10% decrease in adiposity. Cumulative food intake (weeks 5–8) was reduced by amylin and amylin + leptin, but not by leptin alone. Amylin + leptin, but not amylin or leptin alone, reduced plasma triglycerides (by 55%), total cholesterol (by 19%), and insulin (by 57%) compared to vehicle. Amylin + leptin also reduced hepatic stearoyl‐CoA desaturase‐1 (Scd1) mRNA, and increased WAT mRNA levels of adiponectin, fatty acid synthase (Fasn), and lipoprotein lipase (Lpl). We conclude that, in DIO rats, maintenance of amylin + leptin–mediated weight loss requires continued treatment with both agonists, and is accompanied by sustained improvements in body composition, and indices of lipid metabolism and insulin sensitivity.     

Pharmacological actions of the peptide hormone amylin in the long-term regulation of food intake, food preference, and body weight

The ability of amylin to reduce acute food intake in rodents is well established. Longer-term administration in rats (up to 24 days) shows a concomitant reduction in body weight, suggesting energy intake plays a significant role in mediating amylin-induced weight loss. The current set of experiments further explores the long-term effects of amylin (4-11 wk) on food preference, energy expenditure, and body weight and composition. Furthermore, we describe the acute effect of amylin on locomotor activity and kaolin consumption to test for possible nonhomeostatic mechanisms that could affect food intake. Four-week subcutaneous amylin infusion of high-fat fed rats (3-300 microg.kg(-1).day(-1)) dose dependently reduced food intake and body weight gain (ED(50) for body weight gain = 16.5 microg.kg(-1).day(-1)). The effect of amylin on body weight gain was durable for up to 11 wks and was associated with a specific loss of fat mass and increased metabolic rate. The body weight of rats withdrawn from amylin (100 microg.kg(-1).day(-1)) after 4 wks of infusion returned to control levels 2 wks after treatment cessation, but did not rebound above control levels. When self-selecting calories from a low- or high-fat diet during 11 wks of infusion, amylin-treated rats (300 microg.kg(-1).day(-1)) consistently chose a larger percentage of calories from the low-fat diet vs. controls. Amylin acutely had no effect on locomotor activity or kaolin consumption at doses that decreased food intake. These results demonstrate pharmacological actions of amylin in long-term body weight regulation in part through appetitive-related mechanisms and possibly via changes in food preference and energy expenditure.     

Changes in body composition and efficiency of food utilization for growth in young adult female rats before, during and after a period of food restriction.

Changes in body composition were studied in three groups of young adult female rats; the treatments were (1) ad libitum food intake to obtain normal growth, (2) restricted food intake to cause body weight loss, and (3) restricted followed by ad libitum food intake to obtain recovery of lost body weight. In each of the three groups of rats the percentage body water was linearly and negatively correlated with the percentage body fat, the weight of body water was linearly and positively correlated with the weight of body protein, and the ratio of the weight of body protein to water was relatively constant at 1:3.20 +/- 0.02 (mean +/- standard error). The percentage body water in the fat-free body was linearly and negatively correlated with fat-free body weight during normal growth between 109 and 334 g body weight but positively correlated during body weight loss and recovery. During recovery of body weight rats laid down more fat and less protein than during normal growth through the same body weight range and the percentage of digestible energy retained as body tissue was increased.     

Sibutramine alters the central mechanisms regulating the defended body weight in diet-induced obese rats

Chronic administration of sibutramine lowers body weight, presumably by altering brain monoamine metabolism. Here the effect of sibutramine on sympathoadrenal function (24-h urine norepinephrine and epinephrine levels) and arcuate nucleus (ARC) neuropeptide Y (NPY) and proopiomelanocortin (POMC) expression was assessed in diet-induced obese rats fed a low-fat diet. Chronic (10 wk) sibutramine [5 mg. kg(-1). day(-1) ip; rats fed ad libitum and injected with sibutramine (AS)] lowered body weight by 15% but only transiently (3-4 wk) reduced intake compared with vehicle-treated controls [rats fed chow ad libitum and injected with vehicle daily (AV)]. Other rats food restricted (RS) to 90% of the weight of AS rats and then given sibutramine restored their body weights to the level of AS rats when allowed libitum food intake. After reequilibration, RS rats were again energy restricted to reduce their weight to 90% of AS rats, and additional vehicle-treated rats (RV) were restricted to keep their body weights at the level of AS rats for 3 wk more. Terminally, total adipose depot weights and leptin levels paralleled body weights (AV > AS = RV > RS), although AS rats had heavier abdominal and lighter peripheral depots than RV rats of comparable body weights. Sibutramine treatment increased sympathetic activity, attenuated the increased ARC NPY, and decreased POMC mRNA levels induced by energy restriction in RV rats. Thus sibutramine lowered the defended body weight in association with compensatory changes in those central pathways involved in energy homeostasis.     

Ultrastructural morphometry of matrical changes induced by exercise and food restriction in the rat calcaneal tendon.

The ultrastructural morphometry of collagen fibril populations in 24 calcaneal tendons obtained from 12 Fischer 344 rats were studied to elucidate matrical changes induced by food restriction and/or endurance exercise. Rats were randomly assigned to four equal groups: ad libitum control (AC), ad libitum exercise (AE), restricted diet control (RC) and restricted diet exercise (RE) groups. Beginning from 6 weeks of age, animals in the two food restriction groups were fed 60% of the mean food consumption of ad libitum fed rats. Then, starting from 6-7 months of age, the rats in the two exercise groups performed 40-50 min of treadmill running at 1.2-1.6 miles h-1 every day for a total of 10 weeks. Endurance training did not significantly alter body weight, but food restriction with or without exercise resulted in a significant loss of body weight. In ad libitum fed controls, food restriction alone did not significantly alter the mean collagen fibril CSA, but predisposed a preponderance of small-sized collagen fibrils. Endurance training per se induced a significant (32%) increase in mean fibril CSA (P less than 0.05), but this adaptive response to exercise was prevented by food restriction, as indicated by a 33% decline in fibril CSA (P less than 0.05). These findings demonstrate that dietary restriction modifies the adaptation of tendon collagen morphometry in response to endurance training, and that weight loss is better achieved with food restriction than endurance exercise.     

Effects of dietary fat content on adiposity during energy restriction in genetically obese rats.

The effects of the amount of fat provided in a restricted diet on weight loss and body composition were studied in this work. Lean male (Fa/?) Zucker rats were fed a control diet ad libitum. Obese (fa/fa) Zucker rats were divided into three groups: one group was fed a control diet ad libitum and the other two groups were fed 75% energy-restricted diets, which provided 10 or 50% of calories as fat. After 4 weeks, energy restriction normalized body weight but not body composition in the genetically obese rats. Reductions in adipose tissue weights and adipocyte size, without changes in the cellularity, were observed. Differences only reached statistical significance in subcutaneous adipose tissue. A standard fat content in the diet induced the same fat-free mass reduction as a higher amount of this macronutrient, but a greater body fat reduction. This suggests that the restriction of dietary fat, as well as energy, is necessary to achieve dietary management in obesity.     

Does neuropeptide Y contribute to the anorectic action of amylin?

Neuropeptide Y (NPY) is a potent feeding stimulant acting at the level of the hypothalamus. Amylin, a peptide co-released with insulin from pancreatic beta cells, inhibits feeding following peripheral or central administration. However, the mechanism by which amylin exerts its anorectic effect is controversial. This study investigated the acute effect of amylin on food intake induced by NPY, and the effect of chronic amylin administration on food intake and body weight in male Sprague Dawley rats previously implanted with intracerebroventricular (icv) cannulae. Rats received 1 nmol NPY, followed by amylin (0.05, 0.1, 0.5 nmol) or 2 microl saline. Increasing doses of amylin resulted in a dose-dependent inhibition of NPY-induced feeding by 31%, 74% and 99%, respectively (P < 0.05). To determine the chronic effects of i.c.v. amylin administration on feeding, rats received 0.5 nmol amylin or saline daily, 30 min before dark phase, over 6 days. Amylin significantly reduced food intake at 1, 4, 16 and 24 hours; after 6 days, amylin-treated rats showed a significant reduction in body weight, having lost 17.3 +/- 6.1 g, while control animals gained 7.7 +/- 5.1 g (P < 0.05). Brain NPY concentrations were not elevated, despite the reduced food intake, suggesting amylin may regulate NPY production or release. Thus, amylin potently inhibits NPY-induced feeding and attenuates normal 24 hour food intake, leading to weight loss.     

Influence of alterations in meal frequency on lipogenesis and body fat content in the rat.

Rats were allowed to eat only 2 hr per day (meal-fed) or were fed ad libitum (nibbler) for 12 wk; another group of animals was meal-fed for 3 wk and then fed ad libitum (converted I) while the fourth group of rats (converted II) was meal-fed for 3 wk, allowed to nibble for the next 3 wk, meal-fed from the 6th to 9th wk and then returned to ad libitum feeding for the last 3 wk. Body fat gain and food efficiency was increased in converted I rats. The lipogenic capacity of adipose tissue from meal-fed rats was greater than observen meal-fed rats were reverted to ad libitum feeding whereas lipogenic activity increased rapidly when ad libitum fed rats were switched to meal-feeding.     

Effects of rearing temperature and level of food intake on organ size and tissue composition in piglets

Piglets are particularly susceptible to cold and nutritional stress because of their poor insulation and low body fat. The purpose of this study was to examine how ambient temperature and level of food intake affect development in piglets. Thirty-two piglets were reared individually from 14 to 56 days of age in either a cold (10 degrees C) or a warm (35 degrees C) environment. Two feeding regimens, restricted and ad libitum, were used to assess the effect of food intake on organ mass. The ad libitum fed pigs in both environments gained weight at the same rate. Paired t-tests of organ weights of ad libitum fed pigs revealed that the mass of the heart, liver, kidneys, stomach, and small intestine, and total nitrogen and the length of the small intestine were greater in cold-reared than in warm-reared littermates of the same body weight. The skin mass and total fat mass, the lengths of the body, extremities, and individual long bones, and the total surface area were greater in warm-reared than in cold-reared individuals. A regression analysis showed body weight was the most important determinant of size for all tissues measured except fat mass, which was affected slightly more by rearing temperature. Of the organs and tissue components that differed in size in warm- and cold-reared pigs, heart, kidney, stomach, skin, nitrogen, and fat mass, and small intestine length and surface area were generally affected more by rearing temperature than by level of food intake. Liver and small intestine mass and femur length were affected more by level of food intake.(ABSTRACT TRUNCATED AT 250 WORDS)     

Leptin prevents obesity induced by a high-fat diet after diet-induced weight loss in the marsupial S. crassicaudata

The aims of this study were to determine in the marsupial Sminthopsis crassicaudata, the effects of leptin on food intake, body weight, tail width (a reflection of fat stores), and leptin mRNA, after caloric restriction followed by refeeding ad libitum with either a standard or high-fat preferred diet. S. crassicaudata (n = 32), were fed standard laboratory diet (LabD; 1.01 kcal/g, 20% fat) ad libitum fo 3 days. On days 4-10, animals received LabD at 75% of basal intake and then (days 11-25) were fed either LabD or a choice of LabD and mealworms (MW; 2.99 kcal/g, 30% fat); during this time, half the animals (n = 8) in each group received either leptin (2.5 mg/kg) or PBS intraperitoneally two times daily. On day 26, animals were killed and fat was removed for assay of leptin mRNA. At baseline, body weight, tail width, and food intake were similar in each group. After caloric restriction, body weight (P < 0.001) and tail width (P < 0.001) decreased. On return to ad libitum feeding in the PBS-treated animals, body weight and tail width returned to baseline in the LabD-fed animals (P < 0.001) and increased above baseline in the MW-fed animals (P < 0.001). In the LabD groups, tail width (P < 0.001) and body weight (P < 0.001) decreased after leptin compared with PBS. In the MW groups, the increase in tail width (P < 0.001) and body weight (P = 0.001) were attenuated after leptin compared with PBS. The expression of leptin mRNA in groups fed MW were greater in PBS than in leptin-treated animals (P < 0.05). Therefore, after diet-induced weight loss, leptin prevents a gain in fat mass in S. crassicaudata; this has potential implications for the therapeutic use of leptin.     

Effect of long-term food restriction on pituitary sensitivity to cLHRH-I in broiler breeder females

The effect of long-term food restriction on the sensitivity of the pituitary to exogenously administered chicken luteinizing hormone releasing hormone I (cLHRH-I) was investigated in three groups of broiler breeder females fed ad libitum, fed a restricted quantity of food or fed a restricted quantity of food to obtain an intermediate body weight between those of the first two groups. At 16 weeks of age, basal FSH release was higher in ad libitum fed birds, culminating in ovarian development and subsequent oestradiol production by the small follicles. At this age, LH secretion was independent of ovarian feedback factors. In all groups, cLHRH-I was most active in releasing LH in intact and ovariectomized animals and, to a lesser extent, in releasing FSH in ovariectomized birds. At 39 weeks of age, basal FSH concentrations were similar among intact animals of all groups, whereas LH concentrations differed among groups, with higher values in the restricted birds. This food effect was enhanced in ovariectomized birds. Furthermore, the high response to cLHRH-I in the ovariectomized, restricted birds compared with the ad libitum, ovariectomized group suggests an improved sensitivity of the hypothalamic-pituitary axis. In conclusion, birds fed ad libitum showed the highest responsiveness to ovarian factors and to cLHRH-I in releasing FSH in the period before sexual maturity. No effect of amount of feeding could be observed for LH. However, during the egg laying period, LH release by cLHRH-I was highly dependent on amount of feeding and on ovarian feedback regulation. This finding indicates that the amount of feeding can modify the sensitivity of the pituitary to cLHRH-I, and possibly to gonadal hormones, during the laying period.     

Effects of food restriction and social cues on sexual maturation and growth in male musk shrews (Suncus murinus)

In the first experiment, the effects of food availability on growth and reproduction were assessed by placing male musk shrews on 3 different feeding schedules, i.e. fed ad libitum, fed 50% of the amount eaten by the ad-libitum controls or fed 25% of the amount eaten by the ad-libitum controls. After 25 days, growth and sexual maturation were significantly retarded in both of the food-restricted groups compared to the control group. In the second experiment, the combined effects of food availability and social cues were investigated in juvenile males that were either fed ad libitum (during the day) or placed on a restricted diet known to inhibit growth and reproduction. Half of these males were either housed alone or with an adult female (separated from female during the day by a wire barrier, but in full contact at night). The ad-libitum-fed males living with a female ate more food, gained more body weight and were more sexually mature than ad-libitum-fed animals living alone. Furthermore, males in the two food-restricted groups had lower body weights and were sexually immature compared with males in both of the ad-libitum-fed groups. Finally, there were little or no differences in growth and reproduction between animals in the two food-restricted groups. These results suggest that food availability is an important environmental regulator of the timing of sexual maturation, and that stimulatory social cues cannot override the inhibitory effects of an inadequate diet.     

The effect of chronic food and water restriction on open-field behaviour and serum corticosterone levels in rats

In operant conditioning experiments, two methods are commonly used to motivate laboratory rats to perform designated tasks. The first is restricting food so that rats are forced to lose 20% of body weight within one week, followed by maintenance at 80% of the baseline weight for the remainder of the experiment. The second is restricting access to water to 15 min in each 24 h period. These methods are effective in motivating the animals. There is, however, little information available on the effects on performance in tests of behaviour that are not related to operant conditioning. In addition, it is not clear if these commonly used methods of food and water restriction will lead to physiological stress as indicated by an elevation of serum corticosterone. Male rats were either food-restricted to reduce and maintain their weight at 80% of baseline weight, or were restricted to 15 min access to water every 24 h. Activity in the open field was significantly greater in food-restricted rats than in water-restricted or control rats, but freezing behaviour was similar in all experimental groups. Food-restricted rats had a higher mean serum corticosterone level than water-restricted and control rats 37 days after the start of the experimental period. These data suggested that chronically restricting food and maintenance of body weight at 80% of baseline body weight led to significant behavioural changes and physiological stress. In contrast, water restriction did not lead to changes in behaviour or corticosterone levels. A second experiment was conducted to compare the effects of food restriction to 80% of baseline body weight, as described above, with a less stringent protocol in which test rats were initially reduced to 80% of baseline weight, but were then maintained at 80% of an ad libitum fed control rat's weight. Serum corticosterone levels and adrenal gland weights were measured after the initial week of forced weight loss and after maintenance for 21 days. Forced loss of 20% of body weight in the first week led to significantly increased serum corticosterone levels and adrenal gland weights compared to ad libitum fed controls. Serum corticosterone levels and adrenal gland weights in rats maintained at 80% of their initial body weight for 21 days remained higher than ad libitum fed control rats. However, rats maintained at 80% of an ad libitum fed control rat's weight did not differ from control rats in serum corticosterone levels or adrenal gland weights at the end of the 21-day study period. Adjustment of the feeding regimen in this manner eliminated physiological evidence of chronic stress.     

Effect of sibutramine on regional fat pads and leptin levels in rats fed with three isocaloric diets

AIM: The aim of the study was to investigate: a) the differential effect of the three main macronutrients on food intake, fat depots and serum leptin levels and b) the impact of sibutramine on the above parameters in rats fed ad libitum with three isocaloric diets. METHODS: Three groups of male Wistar rats (n = 63) were fed with a high fat diet (HFD), a high carbohydrate diet (HCD) or a high protein diet (HPD) for 13 weeks. In the last three weeks, each group was divided into three subgroups and received sibutramine (S) either at 5 mg/kg or 10 mg/kg, or vehicle. Food intake was measured daily during the last week of the experiment; perirenal and epididymal fat and fat/lean ratio were calculated and serum leptin was assayed. RESULTS: HFD-fed rats demonstrated elevated food intake and higher regional fat depots. S at 10 mg/kg decreased food intake in the HFD and epididymal fat in the HCD group. S also reduced perirenal fat in the HCD and HPD groups. Leptin levels were higher in rats fed with either the HFD or the HPD compared to those fed with the HCD. Moreover, S at 10 mg/kg decreased serum leptin levels in the HPD group. CONCLUSIONS: Results suggest a preferential effect of S on perirenal visceral fat and support the view that body fat loss is greater when its administration is accompanied by a HCD diet. No effect of S on leptin levels was found, besides that expected as a result of the decrease in body fat.     

Sex differences in voluntary locomotor activity of food-restricted and ad libitum-fed rats. Implications for the maintenance of a body weight set-point

1. Male and female Wistar-strain rats were studied under either ad libitum or 23-hour food restriction conditions both with and without access to a running wheel. 2. Daily measures were taken of body weight, food consumption and wheel revolutions. 3. It was observed that food restriction was associated with decreased food consumption and body weight but increased wheel revolutions. 4. Irrespective of feeding regime, females exhibited higher running rates than males.     

Effect of dietary restriction and/or exercise on 23-h metabolic rate and body composition in female rats.

This study examined the effects of three levels of dietary intake [ad libitum fed (AL), moderately severe (MSR), and severe restriction (SR)] and two levels of exercise [cage confinement (CC) and exercise training (E)] on 23-h resting metabolic rate (RMR) and body composition in 47 female Sprague-Dawley rats. At the end of the 9-wk study, the MSR and SR groups weighed approximately 81 and 61%, respectively, of the AL-CC group. RMR was depressed for the MSR and SR groups compared with the AL-CC group. This was true whether expressed on an absolute (ml/min) or relative (ml.min-1.kg-0.75) basis. On a relative basis, which accounts for changes caused by weight loss alone, the RMR decreased by approximately 12 and 19%, respectively, for the MSR and SR groups compared with the AL-CC group. Although E resulted in significant differences in fat mass, percent fat, percent water, and heart mass between the AL groups, there were no significant differences between E and CC groups at either the MSR or SR level of dietary intake for any of the variables measured (i.e., body composition, muscle mass, RMR). Thus E does not appear to affect the composition of lost weight or RMR during diet-induced weight loss for female rats of normal weight.     

Effects of long-term dietary restriction on body temperature are modified with increasing age

Effects of long-term dietary restriction on body temperature and its circadian changes were investigated in 3.5- and 14.5-month-old male Long-Evans rats. Animals were either fed and libitum or kept on a restricted diet for 8 weeks. Purina Lab Chow was constantly available to the ad libitum-fed groups, while half portions of their daily food consumption were given to age-matched diet-restricted groups every day. A highly significant lowering of body temperature in middle-aged diet-restricted (MR) rats was not observed until their food intake had been restricted for 5 weeks compared with that of the middle-aged ad libitum-fed (MA) group as well as that of the young diet-restricted (YR) rats. Eight weeks after diet restriction, both the circadian pattern of body temperature and its diurnal peak-trough difference remained almost unchanged in all four groups, while the average body temperature of MR rats was greatly lower than that of the YR group and that of MA animals. No significant difference in average body temperature was found between the young ad libitum-fed (YA) rats and the MA group. These data suggest that the average body temperature and its circadian changes in ad libitum-fed rats, at least before the age of 14.5 months, is not age-related, while the effect of dietary restriction on body temperature may be modified with increasing age.     

Long-Term Weight Cycling in Female Wistar Rats: Effects on Metabolism

LU, HUIQING, ANNE BUISON, VIRGINIA UHLEY AND K-L CATHERINE JEN. Long-term weight cycling in female Wistar rats: effects on metabolism. Obes Res. Weight cycling (WC) induced by ad-lib and restricted high fat (HF) feeding has been shown to reduce final body weight but not body fat percent in female Wistar rats. We examined the metabolic consequences of this type of WC. Five groups of female Wistar rats were fed a HF diet and the sixth group was fed a low fat diet to serve as a control group. Of the five HF groups, four groups were weight cycled by ad-lib and restricted feeding of the HF diet One of these groups weight cycled three times (HFCYC group) while the remaining three groups weight cycled once only, corresponding to the first, second and the third cycle of the HFCYC group. HF feeding induced hyperinsulinemia, hypertriglyceridemia, insulin resistance and elevated adipose tissue lipoprotein lipase (AT-LPL) activity levels as compared to rats fed the low fat (LF) control diet. WC further increased blood insulin concentrations and insulin resistance in rats with three cycles of WC. However, blood pressure was not affected by HF feeding or WC. The magnitude of increase of AT-LPL was reduced in weight cycled, HF fed obese rats after 15 weeks refeeding. We concluded that even though WC did not enhance weight gain nor impair weight loss, it did facilitate the development of insulin resistance and may predispose animals to diabetes.     

Effect of Chronic Caloric Restriction on the Synchronization of Various Physiological Measures in Old Female Fischer 344 Rats

-A variety of physiological and behavioral parameters which relate to metabolism were continuously monitored in 18 month old female Fischer 344 rats which were maintained on either ad libitum or reduced calorie diets. Caloric restriction (CR) stimulated average motor activity per day, the duration of each feeding episode, food consumed per episode, and water consumed per gram lean body mass (LBM). However, CR limited total food consumption, feeding time, number of feeding episodes per day, total eating and drinking time, and the daily ratio of food consumed to water consumed, CR also decreased average body temperature per day, O₂ consumption, CO₂, production, and respiratory quotient. A variety of parameters concerning water consumption were not affected. CR rats ate their food immediately when food was presented during the light span, while ad libitum fed animals ate numerous small meals throughout the entire dark span. An anticipatory response to restricted feeding was also noted. Total motor activity, metabolism, and body temperature increased just prior to scheduled feeding and reached maximum values shortly after feeding, suggesting that these parameters were highly synchronized to feeding. Females and males were found to respond to caloric restriction in a similar fashion. Dramatic changes in respiratory quotient and body temperature suggest rapid shifts between metabolic pathways (glycolysis to giuconeogenesis) to obtain optimal efficiency. Lower body temperature and metabolism may provide protection against DNA damage, thereby increasing the survival potential of restricted rats. These responses may provide insight into the mechanisms by which caloric restriction acts to extend life span.