Differential early rearing affects response to overfeeding in B6D2F2 mice

Male and female B6D2F2 mice, reared in small (Sm = 4), medium (Md = 8) and large (Lg = 12) litters, were maintained on high-fat, high-carbohydrate (EXP) or chow (CH) diets beginning at 14 weeks. EXP mice consumed more calories and gained more weight than CH mice; these effects were greatest in the Sm animals. Each sex responded similarly. Caloric efficiency was highest in the Sm EXP and male animals. Total body fat in males showed that Sm greater than Md greater than Lg and EXP greater than CH. The thermogenic capacity was measured by total oxygen consumption and body temperature response during acute cold stress, and protein content and cytochrome c oxidase activity in interscapular brown adipose tissue (1BAT). Sm mice had a smaller decrease in temperature and consumed less oxygen per gram body weight than Lg, suggestive of a contributing role of increased insulation. When oxygen consumption was expressed as a function of body weight0.75, EXP greater than CH, but there were no other significant dietary effects. Neither litter size nor diet appeared to affect protein content or cytochrome c oxidase activity in 1BAT. These results show that early rearing experience effects both behavioural and physiological variables associated with the maintenance of adult body weight in mice, but these effects do not appear to be mediated through 1BAT.     

Effects of early rearing experience on feeding behavior in B6D2F2 mice

This work investigated putative factors contributing to the hyperphagia previously observed in mice which had been overfed during the preweaning period by rearing in small litters. In the first study, B6D2F2 mice, reared in small (Sm = 4), medium (Md = 8) and large (Lg = 12) litters, were subjected to a series of diets adulterated with varying concentrations of sucrose octa-acetate (1, 2, 4, and 8%). All animals reduced their food intake in response to the dietary adulteration, with evidence of a dose-response effect, but this response did not differ as a function of litter size. The second study addressed the involvement of the opioid system in the feeding response through the administration of a series of doses of naloxone (0.1, 0.25, 0.5, 1.0, 2.5, and 5.0 mg/kg, or 5, 7.5 and 10.0 mg/kg). Although naloxone treatment did reduce food intake, there was not a clear dose-response relationship. Again, there was no interaction with litter size. These results do not support effects of early rearing on the feeding response to dietary adulteration or to the effects of naloxone administration.     

No persistent effect of preweaning nutrition on postweaning food intake, feeding efficiency, or body energy stores in Long-Evans rats.

The purpose of this study was to determine the relative importance of pre- and postweaning nutrition on body mass, body fat, and feeding efficiency in Long-Evans rats up to a period of 18 weeks following weaning. Female rats were bred and pups were redistributed to form large (14-19 pups), normal (11-13 pups) and small (4 pups) litter groups. Weaned rats were housed as pairs (40 pairs) or singletons (n = 16) and fed either a mixed-fat diet (36.6% fat) or a standard chow diet (13.5% fat). Food intake, body mass, and feeding efficiency were measured at 4, 8, 12, and 18 weeks postweaning. Total body fat and depot fat pad mass were also measured at 18 weeks postweaning. At weaning, pups from small litters were fatter (p less than 0.001), and had a greater mass (p less than 0.03) than pups from large litters. There were no persistent effects of preweaning litter size after covarying for preweaning mass on body mass, and postweaning growth, food intake, feeding efficiency, or body fat accretion. Male rats ingesting the mixed-fat diet had a greater body mass (p less than 0.05), greater body fat accretion (p less than 0.008) and a higher feeding efficiency (p less than 0.001) than their chow-fed counterparts, despite an overall lower energy intake (p less than 0.05). Female rats ingesting the mixed-fat diet had a lower food energy intake (p less than 0.005) and a greater feeding efficiency (p less than 0.001) than chow-fed rats during the early postweaning period, only. Thus, postweaning nutrition may play a more important role in postweaning adult mass and depot fat in freely eating rats than early nutritional experiences.     

Post weaning high fat feeding affects rats' behavior and hypothalamic pituitary adrenal axis at the onset of puberty in a sexually dimorphic manner

Feeding adult rats with high fat (HF) diets can alter their hypothalamic pituitary adrenal (HPA) axis responsiveness. In the present study, we examined the effect of a high fat diet, applied in rats from weaning to puberty, on their behavior and HPA axis status at puberty onset. Wistar rats of both sexes were fed postweaning with two diets containing either 24% fat (high fat, HF) or 4.3% fat (normal chow) by weight. HF enhanced puberty onset in female rats, without increasing body weight gain in either sex, compared with chow-fed animals. In the forced swim test, HF males exhibited a more active behavioral response on the first day, whereas HF females a more passive response during the second day of the test, as compared with their chow-fed counterparts. In the open field test, HF females showed increased sniffing but reduced rearing, compared with chow-fed females and were less explorative than HF males in the central arena. All animals could learn and recall a water maze task though HF males spent more time in the opposite quadrant than chow-fed males during memory test. The HPA axis status of these animals was investigated under basal conditions. Pubertal fat-fed males had lighter adrenals, while females heavier ones, compared with their counterparts. In addition, plasma corticosterone levels of female rats were increased and glucocorticoid receptor levels in their hypothalamus were reduced due to fat diet, while in males no such changes were detected. We conclude that HF feeding during the prepubertal period can affect behavior and the HPA axis of rats at puberty onset, well before the appearance of the obese state, in a sexually dimorphic manner. Fat diet impacted more the female HPA axis, suggesting that their system is more sensitive to fat-induced nutritional imbalance during adolescence. Present data suggest that the fat-induced nutritional imbalance in young females may lead to neuroendocrine dysfunction that in turn may trigger the appearance of stress-related disorders during adolescence.     

不同时间进食高脂或高蛋白食物与肥胖的关系

目的：探讨不同时间段进食高脂肪或者高蛋白饲料对小鼠肥胖程度的影响。方法：将108只3～4周龄健康清洁级雄性昆明小白鼠随机分为3大组：高脂组、高蛋白组和对照组。喂食时间段为：T1（17∶00～19∶00）,T2（22∶00～24∶00）和T3（7∶00～9∶00）。高脂组又分为4小组：HF0,HF1、HF2、HF3。HF0在三时段均喂食高脂饲料,HF1、HF2、HF3分别于时段T1,T2和T3喂食高脂饲料,其余时段喂食普通饲料。高蛋白组分为HP0,HP1、HP2、HP3,分组原理同高脂组。对照组在三个时段均喂食普通饲料。三组小鼠其它时间不予进食,饮水不限,连续喂养8w后,称重,并计算小鼠的体重增加值及测量内脏脂肪系数。结果：高脂组增重：与对照组相比,实验组增重明显,但组间差异没有统计学意义。高蛋白组增重：17∶00～19∶00高蛋白组（HP1）及7∶00～9∶00高蛋白组（HP3）相比对照组有显著增重,三餐高蛋白组（HP0）、22∶00～24∶00高蛋白组（HP2）组、对照组三组之间差别没有统计学意义。无论是高脂组还是高蛋白组的内脏脂肪系数与对照组比较,结果没有统计学意义（P〉0.05）。结论：无论哪一餐进食高脂饲料,或者三餐都进食高脂饲料,相较于对照组都会使小鼠增重明显。而三餐高蛋白组（HP0）相较于对照组没有显著增重;22∶00～24∶00高蛋白组（HP2）相较于对照组没有显著增重;22∶00～24∶00高蛋白组（HP2）相较于三餐高蛋白组（HP0）也没有显著增重。该结论对研究人类肥胖问题有现实参考意义。     

Effects of diet and exercise training on thermogenesis in adult female rats

The effects of a cafeteria diet on body weight gain, food intake, resting metabolic rate (RMR) and the thermic effect of food (TEF) were compared in female Charles River albino rats that were either sedentary or exercise-trained. The food intakes of the exercise-trained rats on the cafeteria diet were increased to the same degree as those of the sedentary rats, however, they gained less body weight and body fat than sedentary controls. The exercise training increased RMR independent of diet, but differentially increased TEF in rats given the cafeteria diet. Conversely, sedentary rats on the cafeteria diet had significantly lower RMR, but their TEF were not different from control animals on lab chow. Thus, in addition to the direct cost of the exercise, training increased thermogenesis (RMR and TEF) which also helped prevent the dietary obesity which normally occurs with cafeteria diets.     

Reproductive consequences of food restricition at low temperature in lines of mice divergently selected for thermoregulatory nesting

Female mice of lines divergently selected for thermoregulatory nesting were mated at 5°C and were fed eitherad libitum or restricted diets. Gestation period and litter size at birth were not affected by food restriction, but both fertility and litter size at weaning were significantly reduced by restriction. The reduction in litter size by restricted females was positively associated with the weight of both females and pups at weaning. The pattern of response to food restriction was generally more conservative than that expected on the basis of r-selection predictions. There was also a significant reduction in the proportion of males weaned by restricted females. Differences among the selected lines in both feeding regimes were generally consistent with the hypothesis that thermoregulatory nesting has a positive genetic correlation with Darwinian fitness at low temperatures.     

Effects of diet and handling on initiation of independent ingestion in rats

The present study examined the effects of dietary manipulation on the age of onset of weaning in rat pups. In Experiment 1, female rats were placed on a standard chow (SC) or high-fat (HF) diet 1 week following mating. Pups were weighed daily from birth to Day 12, then animals were placed into specialized cages for separate recording of food intake of pups and dams. Pups were offered the same diet as their dam, and food intake and body weight were determined twice daily until Day 25. The results demonstrated that pups reared by dams fed the HF diet initiated independent ingestion on Day 16, approximately 24 hr before pups reared by dams fed the SC diet. There were no differences in body weight in pups across the two diets. While few differences were noted across diets in pups' or dams' behavior, HF pups appeared to demonstrate a delay in the establishment of circadian patterns of food intake. In Experiment 2, all dams were maintained on an SC diet until the day after parturition. At that time, dams and litters were placed into specialized cages and divided into four groups: HF/HF, HF/SC, SC/SC, and SC/HF (dam's diet/pup's diet, respectively). The results demonstrated that dams given the HF diet had pups that initiated food intake approximately 2 days before the pups of dams given the SC diet. In addition, pups offered the HF diet, independent of the dam's diet, initiated food intake approximately 0.8 days prior to pups offered the SC diet. Further, by Day 12, HF dams had pups that were heavier than SC dams. The results suggest that the onset of weaning in rats is affected by maternal diet and the weaning diet available to the pup.     

Ontogeny of isolation rearing-induced deficits in sensorimotor gating in rats.

Presentation of a weak stimulus immediately before a startling stimulus decreases the magnitude of the resultant startle response. This phenomenon, termed prepulse inhibition (PPI), provides an operational measure of sensorimotor gating, and is deficient in schizophrenia patients. Clinically observed PPI deficits can be modeled in rodents by housing rats individually from weaning until adulthood. The developmental time course of isolation rearing-induced PPI deficits, however, is unknown. The present studies characterized the ontogeny of isolation-induced PPI deficits and hyperactivity. Separate groups of Sprague-Dawley and Lister hooded rats were either singly housed (ISO) or socially housed (SOC, groups of two to three per cage) upon weaning and then maintained in these housing conditions for different periods of time until assessment of PPI and locomotor activity; animals were tested at time points that roughly corresponded to before puberty (2 weeks postweaning), during puberty (4 weeks postweaning), or after puberty (6-7 weeks post weaning). PPI deficits were seen in Sprague-Dawley ISO rats at either the 4- or 6-, but not the 2-week time points. In contrast, hyperactivity was noted in these animals starting at the 2-week time point. Lister rats showed the same general pattern of ISO-induced effects, with ISO-induced hyperactivity (observed 4 weeks postweaning) preceding ISO-induced PPI deficits (observed 7 weeks postweaning). Therefore, ISO produces dissociable effects on PPI and locomotor activity, with PPI deficits emerging only during or after puberty. ISO might thus provide a useful noninvasive tool with which to study the neural substrates of delayed-onset sensorimotor gating abnormalities.     

Chronic food restriction and reduced dietary fat: risk factors for bouts of overeating

The purpose of this study was to determine the effect of chronic food restriction and reduced dietary fat on feeding behavior and body weight. Young female rats were fed ad lib or food restricted on a low-fat (LF) or a fat-free (FF) diet for 4 weeks. Rats then received 24-h free access to 2 diets, the maintenance diet (LF or FF) plus a novel high-fat (HF) diet (24-h intake test). After the test, all the rats were allowed chronic free access to the HF diet until body weight was stable. During the 24-h test, the restricted groups ate significantly more calories than the ad lib groups, and the FF-restricted rats ate significantly more total food, carbohydrate and protein than the LF-restricted rats; there were no differences between the two ad lib groups. During chronic free access to the HF diet, the formerly restricted rats achieved and defended lower body weights than the formerly non-restricted rats. Throughout the experiment, the ad lib groups had more body fat than the restricted groups independent of the dietary subgroup. Hence, a history of chronic food restriction predisposes to consuming more food in acute feeding situations, particularly when dietary fat is reduced, and lowers the level of body weight maintained and defended. Chronic food restriction accompanied by reduced dietary fat may increase risk for bouts of overeating.     

Effects of preweaning nutrition on weight gain during pregnancy in mice

Previous work has shown that preweaning litter size affects the response of adult mice to dietary induced obesity, with animals reared in small litters showing increased hyperphagia and weight gain. The present work addressed whether a similar effect would be seen in the weight changes normally accompanying pregnancy and lactation. B6D2F2 mice were reared in small (4), medium (8) and large (12) litters. Adult females from each of these conditions were mated with males from medium litters and their body weight and food intake measured throughout pregnancy and lactation. Food intake increased during pregnancy and correlated with the dams' litter size, but the amounts consumed by all groups appeared similar. This was also true of maternal weight gain during pregnancy, pup weight and litter size. During lactation, the only differences were that animals which had been reared in large litters ate more food and weaned heavier pups than those in medium litters. These results differ from those previously obtained on dietary induced obesity, supporting different regulatory mechanisms in the two conditions.     

Returning 'cafeteria-fed' rats to a chow diet: negative contrast and effects of obesity on feeding behaviour

Two experiments examined the feeding behaviour and body weight changes of rats returned to a standard chow diet after prolonged periods of cafeteria feeding. In the first, both overweight (ad lib fed) and 'normal' weight (fed a restricted ration of cafeteria foods) cafeteria rats became hypophagic compared to chow-fed rats following their return to chow feeding. However, the overweight rats' hypophagia was initially more severe and was longer lasting. In the second experiment, analysis of meal patterns recorded throughout the first 4 weeks on chow after 26-32 weeks of ad lib cafeteria feeding showed that the hypophagia was due to a reduction in mean meal size (MMS) and meal frequency (MF). Food intake and MMS subsequently recovered to within control levels (by 2-3 weeks), but MF remained persistently low. There was a decrease and then a recovery in eating rate (ER) which paralleled the changes in MMS. The previously cafeteria-fed rats lost only 60% of their excess body weight. These findings are interpreted in terms of a negative contrast effect (changes in MMS and ER) and an inhibitory action of increased adiposity on feeding (affecting mainly MF).     

Effects of a gastric implant on body weight and gastrointestinal hormones in cafeteria diet obese rats

In order to evaluate the effectiveness of a gastric implant in an animal model of dietary obesity, silicone implants (2.5 ml) were inserted into the stomachs of male rats maintained on a chow or "cafeteria" diet. At the time of implantation, the cafeteria fed rats weighed 14% more than chow fed controls. Overweight cafeteria fed animals lost weight in response to the gastric implant, whereas control chow fed animals did not. Both implant groups had significant increases in stomach weights in contrast to sham implant groups, but the increase was much less in the cafeteria diet group. The fasting plasma levels of the gastrointestinal hormones, gastrin and pancreatic polypeptide, and oxytocin (a marker of vagal afferent function) were measured by radioimmunoassay. Cafeteria fed sham or implanted animals had significantly higher fasting levels of plasma oxytocin and gastrin, and significantly lower plasma levels of pancreatic polypeptide than the chow fed groups. These studies demonstrate that the gastric implant has more effect on weight in overweight animals on a palatable mixed diet, perhaps related to both mechanical and neural factors.     

Vitamin A deficiency and the development ofLitomosoides carinii (Nematoda,Filarioidea) in cotton rats

Summary This paper demonstrates that vitamin A deficient (A–) cotton rats are more susceptible to infection withLitomosoides carinii than normal (A+) cotton rats. However, embryogenesis is frequently retarded in female worms from A– hosts.Groups of young cotton rats were depleted of their liver stores of vitamin A by feeding them a vitamin A free diet from weaning. From 6 weeks of age this diet was supplemented with either 2, 5, 10, 25 or 100 IU vitamin A per 100 g body weight per day and half the animals in each group were infected withL. carinii. At autopsy, 51 days post-infection, serum vitamin A levels were proportional to vitamin A intake but were unaffected by infection (P<0.05). A+ cotton rats grew more rapidly and gained more weight than A– ones; infected animals gained less weight than their uninfected controls. More parasites developed in rats fed either 2 or 5 IU vitamin A than those fed either 10, 25 or 100 IU (P<0.02) and parasites from the 5 IU group were significantly longer than those from all other groups (P<0.02).However, microfilarial development was retarded in female worms from A– animals as compared with A+ ones.     

Ability of omega-3 fatty acids to restore the impaired glucose tolerance in a mouse model for type-2 diabetes. Different effects in male and female mice

Mice of both sexes were fed diets with 80 per cent animal or vegetable fat for 3 months. Half of the animals also received SuperEPA, which contains 61% omega-3 fatty acids. At the end of the feeding period the mice receiving animal fat had gained more weight than the controls and the mice receiving vegetable fat, and all fat diet groups, irrespective of sex or kind of diet, had become hyperglycaemic and had impaired intravenous glucose tolerance. The decay in plasma glucose during the tolerance tests was, however, significantly slower in the groups getting animal fat than in the groups getting vegetable fat. Supplementation with omega-3 fatty acids only affected the male mice receiving the animal fat diet. Thus, these mice gained less weight, and both the hyperglycaemia and the impairment of the glucose tolerance were significantly less pronounced in this group than in the male mice fed animal fat without SuperEPA. In the groups eating fat diets, the plasma total cholesterol levels increased 50-100 per cent during the first 2 weeks of the experiment and then plateaued. In both sexes HDL-cholesterol averaged approx. sixty-five per cent of the total cholesterol content at the start of the experiment and was not changed significantly during the feeding period. It is concluded, that omega-3 fatty acids do not seem to be suitable as a general means of ameliorating impaired glucose tolerance. It is further suggested that the fat-fed mouse may be a useful animal model for further studies of the regulation of metabolism in type-2 diabetes.     

Effect of increased growth rate during the suckling period on subsequent body weight and muscle weight to body weight ratio

The effect of increased growth rate during the suckling period on subsequent body growth rate and muscle weight to body weight (MW/BW) ratio was examined in inbred and outbred male and female mice. Growth rate during the suckling period was increased by reducing litter size to 4 pups within six hours of birth. Body weight, MW/BW ratio, and dry weight to wet weight (DW/WW) ratio for the soleus, tibialis anterior, extensor digitorum longus, biceps brachii, and heart muscles were measured at 4, 8, 16, and 24 weeks of age. The results indicate that increasing growth rate during the suckling period results in an increased body weight at 24 weeks of age in outbred male and female mice; whereas, in inbred male and female mice body weight is greater at 4 weeks of age but by 8 weeks of age the mice raised in normal litters have "caught up" with those raised in small litters. MW/BW ratio is increased in several muscles during the suckling period but returns to normal during the post weaning period.     

Early protein malnutrition in the rat: Behavioral changes during rehabilitation

Behavioral development was studied in 2 groups of rats during the postweaning period. Pups were selected from litters nursed by dams fed either a standard protein (25% casein by weight) or a low protein diet (12% casein) during lactation. Two pups from each litter were housed together and fed the control diet throughout rehabilitation Behavioral observations were made by repeated time-lapse photography at 5-day intervals. Differences in h ome cage behavior were observed at the onset of rehabilitation in the postnatally malnourished rats. Increased feeding behavior was observed during the 1st week of rehabilitation. Locomotor behavior was depressed during the rehabilitation period in the experimental animals. Climbing activity, however, was significantly greater. Self-grooming activity was elevated throughout rehabilitation in post-natally malnourished animals. During the course of rehabilitation, the behavioral differences between the 2 groups gradually disappeared.     

The behavioral sequela following the prevention of home-cage grid-climbing activity in C57BL/6 mice

Several studies have demonstrated that the early postweaning phase (3-7 weeks of age) is a crucial ontogenic period for rodent neurobehavioral development. During this phase, both brain and behavior are highly sensitive to environmental variations (i.e., changes in the standard housing conditions). In the present study, male and female C57BL/6 mice were housed at weaning in cages provided with a Plexiglas lid, and thus, they were deprived of the opportunity to perform climbing activity on the cage grid--a major component of mouse behavior in standard laboratory environments. At early adulthood (7-10 weeks old), mice underwent an extensive battery of behavioral tests. The present study demonstrates for the first time the psychological, sex-specific relevance of home-cage grid-climbing activity in mice, showing that its prevention alters fear-conditioned responses in mice of both sexes and induces psychotic-like and anxious behaviors in females only. The data further highlight the importance of the early postweaning phase for the study of environmentally induced neurobehavioral plasticity and the design of animal models of psychiatric disorders on the basis of environmental manipulation in early postweaning life.     

Energy intake of rats fed a cafeteria diet

The proportion of lipid, carbohydrate and protein energy self-selected by male and female rats from a cafeteria diet has been studied for a 48-day period (36-day in female rats). The diet consisted in 12 different items and was offered daily, in excess and under otherwise standard conditions, to rats--caged in groups of three--from weaning to adulthood. Groups of control animals were studied in parallel and compared with the cafeteria groups. Cafeteria diet fed groups of rats ingested more energy and lowered their metabolic efficiency with age. Male rats ate more than females and increased their body weight even after female practically stopped growing. There was a wide variation in the aliments consumed each day by the cafeteria-fed rats. However, the proportion of lipid, protein and carbohydrate the rats ate remained constant. Male rats ingested more lipid than females. Carbohydrate consumption was constant in control and cafeteria fed groups of rats independently of sex. Protein consumption was higher in cafeteria rats than in controls, but the differences were not so important as with liquid. Fiber content of the cafeteria diet was lower than that of the control diet. The cafeteria diet selected by the rats was, thus, hypercaloric and hyperlipidic, with practically the same amount of carbohydrate than the control diet, slightly hyperproteic and, nevertheless, remarkably constant in its composition with respect to time. Cafeteria rats had a higher water intake than controls. All these trends were maintained despite the observed changes in the animals' tastes and their differential consumption of the ailments of the diet.     

Hyperactivity and obesity: The interaction of social isolation and cafeteria feeding

Rats were reared in social isolation or in social groups of 4 or 5 rats per cage from weaning and were fed either a lab chow diet or a diet of 4 palatable foods (cafeteria diet), in addition to the lab chow. The hyperactivity of isolation-reared rats appears to be a reactivity to novel environmental stimuli, since it was seen only in the 0.5 hr tests and not in the near 24 hr test. It was found that hyperactivity and increased body weight can develop within as few as 7 to 10 days in rats reared in isolation from weaning. Cafeteria feeding enhanced activity in isolation-reared rats, but suppressed it in group-reared rats. Isolation-reared rats fed a cafeteria diet had strong, stable preferences for their most preferred food over the 25 days of measurement. Rats reared in isolation had significantly different food preferences, as compared with rats reared in groups. Cafeteria fed rats had a significantly greater calorie intake and body weight than rats fed lab chow. On analysis, cafeteria fed rats had significantly greater carcass energy and an increased amount of parametrial white adipose tissue as compared with rats fed only lab chow. The interscapular brown adipose tissue (IBAT) weights of cafeteria fed rats were also greater. However, as there was no difference between the cafeteria and chow fed rats in the total amount of protein in the IBAT, it was concluded that the increased weight of the IBAT did not reflect a genuine hypertrophy of the tissue.