The food intake of rats during pregnancy and lactation

Quantities of food required by Sprague-Dawley rats during gestation and lactation and in the post-lactation period were examined. Rats allowed to eat ad libitum during pregnancy consumed quantities of food only slightly greater than the amount reported to be the average intake of pregnant Sprague-Dawley rats (20 g/day). Rats delivered their pups on day 22 or day 23 of the gestation period, but regardless of the day of delivery, the food intake of each rat decreased on day 21 of pregnancy and then decreased a second time on the day of parturition. During lactation, food consumption of the rats soon exceeded the amount reported as the average intake of lactating rats (30-35 g/day). Food intake was found to escalate from 12.2 +/- 3.1 g/rat on day 0 of lactation, the lowest intake in the study, to 94.4 +/- 23.7 g on day 21 of lactation. However, in the latter part of the lactation period, the intake represented the combined food intake of dams and pups. Eight days in the post-lactation period were required for food intake of dams to return to a level near that recorded at the beginning of pregnancy.     

Effects of premature weaning and diet on lung growth and appearance of adenylate cyclase activator in rat lung

Early weaning of rat pups on day 16 to semi-ground Purina chow food and drinking water, ad libitum, delayed growth of body and lungs, and the appearance of adenylate cyclase activator (ACA) in lung after day 22. However, early weaning of pups to either milk or a gel diet containing semi-ground Purina chow food, agarose gel, water (30:1:69, w/w), and drinking water, restored lung and body growth and the appearance of ACA to control values. Early weaning of pups to dry semi-ground Purina chow food and drinking water also induced a transient rise in ACA on day 19. This early rise in ACA was completely absent in pups weaned on day 16 to milk, whereas it persisted in pups weaned similarly to a gel diet. Interestingly, lung glycogen decreased on day 19 in pups weaned early to dry semi-ground Purina chow food without (group 2) or with triiodothyronin administration (group 3), and on day 25 after normal weaning on day 22 (Nijjar, M.S. Biochim. Biophys. Acta 586: 464–472,1979). These data indicate 1) that reduced food intake (starvation) in pups weaned on day 16 to dry semi-ground Purina chow food was responsible for the delayed growth of body and lung, and the delayed appearance of ACA in lung after day 22, and 2) that a change in diet from milk to Purina chow food and associated alterations in hormones, possibly cortisol and insulin, were responsible for the appearance of ACA in rat lung. It would appear that reduced intake of food (starvation) and associated changes in hormones in rat pups at weaning induce ACA in lungs, stimulating adenylate cyclase to produce more cyclic AMP. A rise in cyclic AMP may initiate a cascade of enzymic reactions resulting in enhanced metabolism of glycogen to intermediates which are utilized for the production of energy during the time that the exogenous source of energy i.e. food, is restricted.     

Leptin serum concentration,food intake and body weight in rats whose mothers were exposed to malnutrition during lactation

We had shown that adult animals, whose mothers were submitted to protein or energy restriction during lactation, differ from controls in their body weight and thyroid function. The aim of this study was to evaluate, from birth through six months of age, leptin serum concentration, body weight and food intake in animals whose mothers received protein or energy restricted-diet during lactation as follows: control (C)-23% protein; protein-restricted (PR)-8% protein; energy-restricted (ER)-23% protein, in restricted quantity, according to the mean ingestion of the PR group. After weaning (day 21) all pups had free access the control diet. Body weight of pups from PR mothers were always lower than those from controls (p < 0.05), while body weight of pups from ER mothers surpassed that of the C group significantly at 140 days of age. The food intake was lower in both offspring from PR and ER mothers, normalizing on the 32th day in pups from ER mothers and on the 52th day in pups from PR mothers. Leptin serum concentration in both offspring from PR and ER mothers were significantly decreased on the 12th day (p < 0.05) and increased on the 21st day (p < 0.05) compared to control. After weaning there was no differences among the groups. It is possible that changes in leptin concentration during lactation in the offspring of malnourished groups could permanently modify the setpoint for body weight control.     

In a hypergravity environment neonatal survival is adversely affected by alterations in dam tissue metabolism rather than reduced food intake.

Exposure of rat dams to hypergravity during pregnancy is associated with increased pup mortality, reduced food intake, and decreased rates of glucose oxidation and lipogenesis in mammary tissue. We hypothesized that increased pup mortality is due to changes in maternal metabolism and not to reduced food intake of dams. Effects of hypergravity on rate of glucose oxidation and lipogenesis in mammary, liver, and adipose tissue were measured in rat dams centrifuged at 2.0 G [hypergravity (HG)], kept at 1.0 G (control), or fed to match the intake of HG rats (pair fed) from gestation day 11 (G11) until G21 or postpartum day 3 (P3). Body weight, percent body fat, metabolizable energy, and nitrogen balance were significantly less in HG dams compared with controls (P<0.05); however, these factors were not different between HG and pair-fed dams. By P3, 100% of control and pair-fed pups survived, while only 49% of HG pups survived. At G21, rates of glucose oxidation and lipogenesis in mammary and adipose tissue were less in HG than in control and pair-fed dams (P<0.1 and P<0.05). In liver, at G21, the rate of lipogenesis was greater in HG than control and pair-fed dams (P<0.01); at P3, lipogenesis was greater in control than HG and pair-fed dams (P<0.05). Gene expression of ATP citrate lyase, acetyl-CoA carboxylase, and fatty acid synthase increased in liver from pregnancy to lactation in control and pair-fed dams but not HG dams. Thus reduced food intake and body mass due to hypergravity exposure cannot explain the dramatic decrease in HG pup survival.     

Effect of insulin and 2-deoxy-d-glucose on the food intake of infant rats

The effects of glucoprivation on the food intake have been determined in infant rats up to weaning. It was found that insulin reduced the milk intake of 9, 13 and 17-day-old males and females for three hours after treatment. In 24-day-old pups food intake increased for three hours after insulin administration, and decreased during the next 21-hour period. 2-deoxy-D-glucose increased the food intake in 28-day-old rat pups only. It was concluded that the inability of rat pups to correct glucoprivation by a subsequent increase of food intake is a consequence of the inadequate development of hypothalamic regulatory mechanisms. Glucoprivation stimuli are ineffective inducers of short-term hyperphagia of rat pups until the age of 24-28 days.     

Effect of weaning time on the growth rate and food intake of the spiny mouse pup

The spiny mouse Acomys cahirinus produces well-developed pups although it is a relatively small mammal (45 g). We envisioned two opposing hypotheses on the effect of early weaning on the growth rate of pups. The first predicts little effect since the increase in energy intake of dams above non-reproducing females is relatively low, suggesting that pups consume a large portion of their energy as solid food, and the pups are very well developed at birth. The second predicts a substantial effect since the 'index of precociality', that is the energy intake for maintenance of a pup as a proportion of that predicted for a rodent of its body mass, falls within values for altricial rodents, suggesting an extended maternal dependence of the young. To test these hypotheses, we measured the growth rate and food intake of pups weaned after either 7, 14, 21 or 28 days. Only three of 12 pups weaned after 7 days survived and, consequently, the latter hypothesis was supported. All pups weaned at 14–28 days survived. There was a significant decrease in growth rate during the first day after weaning in pups weaned at 7, 14 and 21 days but not after 28 days, suggesting that pups did not require parental care by day 28. Peak growth rate in pups weaned at 14 days occurred in the second week but occurred in the third week in pups weaned at 21 and 28 days. In spite of these differences, pups in all treatments had similar body mass at 64 days, indicating compensatory growth. We concluded that pups of A. cahirinus are precocial from a morphological aspect in that they are well developed at birth but altricial from a nutritional aspect in that they require extended maternal support.     

The effect on growth of feeding supplemental milk or baby food to the suckling rat

Suckling rats were fed synthetic rat milk or baby food as dietary supplements amounting to 10% of their total expected daily caloric intake from day 10 to day 16 of life. On day 17, their body lipid levels were significantly higher than those of control pups, and they remained high throughout a 6-week postweaning period of ad libitum food intake. Protein content (at 17 and 60 days of age) was similar in experimental and control groups. Seventeen-day-old pups that had been fed supplemental baby food showed a small but significant increase in DNA levels but no accompanying increase in lean body mass. Rats that received supplemental milk weighed more than either those that received baby food or controls at 17 days of age; however, both experimental groups weighed considerably more at weaning (21 days) than controls. At 60 days of age, their weights were again similar to those of control rats.     

The development in infant rats of kassinin's potent and selective control of cell-dehydration thirst

In infant rats, kassinin exerts its antidipsogenic effect in the very early stages of neonatal life (2nd-3rd day). The inhibition of cell-dehydration drinking appears in rats of 2 days, and attains adult levels in pups of 9 days. Instead, the thirsts induced by suckling deprivation or by intracerebroventricular angiotensin II are inhibited by kassinin precociously (3rd day), but are unaffected by it in rats of 12-15 days. Kassinin also inhibits milk intake very early (3rd day) and this effect also disappears at 12 days of age. The pattern of ontogenetic results described here may be that of a brain kassinin-like tachykinin that, in the course of the development of the neural structures on which it acts, gains potent and selective control of cell-dehydration thirst.     

Functional changes of the small intestine in over- and undernourished suckling rats support the development of obesity risk on a high-energy diet in later life

To investigate the relationship between early nutritional experience, ontogeny of the small intestinal functions and predisposition to obesity development, the following experimental models of male Sprague-Dawley rats were used: 1) rats in which the quantity of nutrition was manipulated from birth to weaning (day 30) by adjusting the number of pups in the nest to 4 (SL), 10 (NL) and 16 pups (LL) and 2) littermates of SL, NL and LL rats fed either a standard or a hypercaloric diet from days 80 to 135 of age. The overfed SL pups were overweight after day 15 and became permanently obese, whereas the underfed smaller LL pups, due to accelerated growth and enhanced food intake from day 30 to day 35, attained a body fat level that did not differ from normally fed NL rats. Moreover, a significantly increased duodenal and jejunal alkaline phosphatase (AP) activity was found in SL and LL rats and these acquired somatic and intestinal characteristics persisted from weaning throughout life. Eight weeks of high-energy diet feeding elicited a similar pattern of intestinal response in SL and LL rats that was clearly different from NL rats. Despite energy over-consumption in these three groups, both SL and LL rats still displayed enhanced AP activity and showed a significant increase in protein/DNA ratio accompanied with a significant body fat accretion. These results indicate that the postnatally acquired small intestinal changes induced by over- and undernutrition could be involved in the similar predisposition to obesity risk in later life when caloric density of the diet is raised.     

Obesity and changes of alkaline phosphatase activity in the small intestine of 40- and 80-day-old rats subjected to early postnatal overfeeding or monosodium glutamate

To investigate the relationship between development of obesity and the small intestinal functions two experimental models of male Wistar rats were used in the present work: 1) early postnatally overfed rats, nursed from birth to weaning in small litters (SL, 4 pups/nest), and 2) neonatally monosodium glutamate treated rats (MSG 2 mg/g b.w. administered s.c. for 4 days after birth) submitted to the same early nutritional manipulation. After weaning, all animals had free access to a standard pellet diet and at 40 and 80 days of age their body weight, body fat content and food consumption as well as changes of the brush-border-bound duodenal and jejunal alkaline phosphatase (AP) activity were compared with parameters of the offsprings raised under normal feeding conditions (NL, 8 pups/nest). At 40 and 80 days of age the postnatally overfed pups from SL nests became heavier, displayed a significantly increased epididymal plus retroperitoneal fat pad weight (P<0.01) and significantly higher AP activity in both segments of the small intestine (P<0.01) in comparison with rats nursed in NL nests, although their mean daily food intake did not differ from that of non-obese rats during the postweaning periods examined. In contrast, the same treatment of MSG rats had only a small effect on late appearance of obesity, i.e. in early postnatally overfed and normally fed MSG rats a similar pattern of body weight, food intake, adiposity and AP activity was found after weaning. The effect of MSG-treatment was also accompanied by the appearance of normophagia, hypophagia and stunted growth on day 40 and day 80, respectively. Moreover, the size of fat depots and the increase of brush-border-bound AP activity in MSG rats belonging to the SL and NL groups was quantitatively similar to the values size of these parameters observed in SL obese rats subjected to early postnatal overnutrition. These results indicate that postnatal nutritional experience (overnutrition) may represent a predisposing factor in control rats from small litters for the development of obesity in later life. Permanently increased small intestinal AP activity observed after weaning in both models of obesity when hyperphagia is not present suggest that these functional changes and associated alterations in food digestion could be a component of regulatory mechanisms contributing to the maintenance of their elevated body fat weight.     

Involvement of the GHSR in the developmental programming and metabolic disturbances induced by maternal undernutrition

The mismatch between maternal undernutrition and adequate nutrition after birth increases the risk of developing metabolic diseases. We aimed to investigate whether the hyperghrelinemia during maternal undernourishment rewires the hypothalamic development of the offspring and contributes to the conversion to an obese phenotype when fed a high-fat diet (HFD). Pregnant C57BL/6 J, wild type (WT) and ghrelin receptor (GHSR)^−/− mice were assigned to either a normal nourished (NN) group, or an undernutrition (UN) (30% food restricted) group. All pups were fostered by NN Swiss mice. After weaning, pups were fed a normal diet, followed by a HFD from week 9. Plasma ghrelin levels peaked at postnatal day 15 (P15) in both C57BL/6 J UN and NN pups. Hypothalamic Ghsr mRNA expression was upregulated at P15 in UN pups compared to NN pups and inhibited agouti-related peptide (AgRP) projections. Adequate lactation increased body weight of UN WT but not of GHSR^−/− pups compared to NN littermates. After weaning with a HFD, body weight and food intake was higher in WT UN pups but lower in GHSR^−/− UN pups than in NN controls. The GHSR prevented a decrease in ambulatory activity and oxygen consumption in UN offspring during ad libitum feeding. Maternal undernutrition triggers developmental changes in the hypothalamus in utero which were further affected by adequate feeding after birth during the postnatal period by affecting GHSR signaling. The GHSR contributes to the hyperphagia and the increase in body weight when maternal undernutrition is followed by an obesity prone life environment.     

Maternal treatment with oleoyl-estrone induces resistance to lipid accrual in their descendants

Objective: To determine whether treatment of rat dams with oleoyl‐estrone (OE) has an effect on the offspring's long‐term response to diet restriction during lactation. Methods and Procedures: Control, OE‐treated, and diet‐restricted dams were treated up to day 15 of lactation. Changes in food intake and body weight were recorded for dams and their pups. After weaning, pups received a 4‐week standard diet followed by a 4‐week period of high‐fat diet. Lipid, protein, and energy content of pups plus energy intake and efficiency. Serum metabolites (glucose, urea, and cholesterol) and serum hormones (adiponectin, leptin, insulin, and sexual hormones). Results: Neither pups from dams in the OE‐treated nor in the diet‐restricted group showed significant changes in weight, though these two groups ingested 79% of food ingested by controls. At weaning, the pups from OE‐treated rats were smaller than those of the control or diet‐restricted groups. These pups maintained the differences in size and lipid content during the 4‐week standard‐diet period, whereas pups from diet‐restricted dams showed a sharp decrease in their lipid content. During the 4 weeks of high‐fat diet, the male offspring from OE‐treated dams increased the difference in lipid content in relation to the pups from control dams whereas in females the differences decreased. Female offspring from diet‐restricted dams showed the most marked changes in metabolite and hormone levels in relation to controls. Discussion: Treatment of lactating dams with OE programs the metabolic response of their offspring to resist the challenge of a high‐fat diet that would lead to obesity in adulthood.     

The effect of peripheral administration of peptides on food intake, glucose and insulin in wolf pups

In the studies reported here we demonstrate that bombesin decreases food intake in wolf (Canis lupus) pups without altering glucose or insulin levels. A high dose of cholecystokinin-octapeptide (CCK, 5 μg/kg) decreased food intake. CCK produced a transient increase in insulin, without altering glucose. Glucagon (0.5 mg/kg) failed to decrease food intake despite producing a marked hyperglycemia and hyperinsulinemia. Calcitonin was ineffective at decreasing food intake, although it did decrease the time spent feeding. These studies suggest a potential role for peripheral peptides in food regulation in the wolf.     

Intestinal microflora and obesity in rats

The relationship was evaluated between early nutritional experiences, the intestinal microflora and the small intestinal functions in the mechanism of predisposition to obesity development. Male Sprague-Dawley rats were used in which the quantity of nutrition was manipulated from birth to weaning (day 30) by adjusting the number of pups in the nest to 4 small litters (SL) and 10 normal litters (NL) and fed a standard diet from days 30 to 40 of age. After 40 d, the postnatally overfed SL pups became heavier, displayed significantly enhanced adiposity, body mass gain and food intake as well as a significantly higher jejunal alkaline phosphatase and maltase activity than in rats nursed in NL nests. The effect of different early nutrition was also accompanied by the appearance of significantly decreased Bacteroides and significantly increased enterococci and lactobacilli of obese rats than in lean NL rats. The amounts of Bacteroides were negatively correlated with fat pad mass, body mass, body-mass gain and food intake whereas enterococci and lactobacilli were correlated positively with the same parameters. Our results demonstrate that postnatal nutritional experience may represent a predisposing factor influencing ontogeny of small intestine function and development of intestinal microbial communities. The acquired changes and associated alterations in food digestion could be a component of regulatory mechanisms contributing to the development of obesity and its maintenance in later life.     

Absence of anorectic effect to acute peripheral leptin treatment in adult rats whose mothers were malnourished during lactation.

Diets with restricted energy or protein during lactation programs body weight in the adult offspring. We have investigated the hypothesis that protein or energy-restricted diets during lactation alter the feeding response to peripheral leptin treatment of the adult offspring. Five Wistar rats were randomly assigned to one of the following groups on the day that the offspring were born: C, control diet with 23% protein; PR, protein restricted diet with 8% protein; and ER, energy-restricted, receiving the control diet in restricted quantities, which were calculated according to the mean ingestion of the PR group. After weaning (day 21), two animals from each litter (10 pups in each group) were randomly selected and placed together in the cage with free access to water and standard diet until 150 days of age, when they were tested for its response to either leptin (0.5 mg/kg body wt ip) for groups Clep, PRlep and ERlep or saline vehicle for groups Csal, PRsal and ERsal on food intake. In the control groups, food intake was reduced two hours (36%), four hours (41%) and six hours (25%) after leptin treatment. In contrast, no response was observed to leptin treatment in the PRlep and ERlep groups, suggesting leptin resistance. We demonstrated the development of resistance to the anorectic leptin effect and its program in a critical life period associated to nutritional and hormonal factors.     

Chronic treatment with a stable obestatin analog significantly alters plasma triglyceride levels but fails to influence food intake; fluid intake; body weight; or body composition in rats

Obestatin (OB(1-23) is a 23 amino acid peptide encoded on the preproghrelin gene, originally reported to have metabolic actions related to food intake, gastric emptying and body weight. The biological instability of OB(1-23) has recently been highlighted by studies demonstrating its rapid enzymatic cleavage in a number of biological matrices. We assessed the stability of both OB(1-23) and an N-terminally PEGylated analog (PEG-OB(1-23)) before conducting chronic in vivo studies. Peptides were incubated in rat liver homogenate and degradation monitored by LC-MS. PEG-OB(1-23) was approximately 3-times more stable than OB(1-23). Following a 14 day infusion of Sprague-Dawley rats with 50 nmol/kg/day of OB(1-23) or a N-terminally PEGylated analog (PEG-OB(1-23)), we found no changes in food/fluid intake, body weight and plasma glucose or cholesterol between groups. Furthermore, morphometric liver, muscle and white adipose tissue (WAT) weights and tissue triglyceride concentrations remained unaltered between groups. However, with stabilized PEG-OB(1-23) we observed a 40% reduction in plasma triglycerides. These findings indicate that PEG-OB(1-23) is an OB(1-23) analog with significantly enhanced stability and suggest that obestatin could play a role in modulating physiological lipid metabolism, although it does not appear to be involved in regulation of food/fluid intake, body weight or fat deposition.     

Food restriction induced thyroid changes and their reversal after refeeding in female rats and their pups

In the present study, two groups of pregnant female rats were submitted to food restriction (24 h fast versus 24 h diet intake) from the 14th day of pregnancy until either the 14th day (group B) or the 4th day after parturition (group C). All pups and their mothers were sacrificed on day 14 after delivery. The body weight of the 14-day-old pups (group B) was 46% less than the controls (group A). Free thyroxine and free triiodothyronine levels in the plasma were reduced by 44 and 16% in pups and by 20 and 36% in their mothers, respectively. These reductions were correlated with a decrease in thyroid iodine content of the pups (-50%) and their mothers (-24%). Radioiodine uptake (131I) by the thyroid gland of pups was significantly increased by 27%. Plasma TSH levels were decreased by 38% in pups and by 44% in dams. Morphological changes in thyroid glands were observed in energy restricted dams and in their pups. Some of follicles in pups were empty. Moroever in dams, we noted the presence of peripheral resorbed vacuoles, sign of thyroid hyperactivity. After a refeeding (group C) period of ten days, total recovery occurred in plasma thyroid hormone levels (FT4 and FT3) and in thyroid iodine contents of pups in spite of a partial recovery of body weights and plasma TSH levels. In dams, a partial recovery occurred in plasma thyroid hormone levels in spite of total recovery in thyroid iodine contents, while plasma TSH levels exceeded control values. A significant amelioration in thyroid histological aspects was observed in pups and their dams.     

Leptin treatment during the neonatal period is associated with higher food intake and adult body weight in rats.

For this study, we have determined the effects of neonatal leptin treatment on the evolution of body weight. Experiment 1: pups were divided into two groups: LepF - injected with leptin (8 micro g/100 g of body weight) for the first 10 days of lactation and control (C) - receiving saline. Experiment 2: pups were divided into two groups: LepL - injected with the same leptin concentration of experiment one for the last 10 days of lactation, and C, which received saline. Body weight and food intake were monitored until age 150 days, after which leptin concentrations were measured by ELISA. The LepF group had a significant increase in body weight (p < 0.05) from day 98 onward, in food intake (p < 0.05) from day 74 onward, and higher serum leptin concentration compared to the control (108 %, p < 0.05). The LepL group had a significant increase in body weight (p < 0.05) from day 113 onward, in food intake from day 121 onward (p < 0.001), and higher serum leptin concentration compared to controls (6.9 %, p < 0.05). These results suggest that both periods of lactation constituted a critical window for body weight and food intake programming, but the effects are more marked when the leptin is injected within the first ten days.     

Alterations in the activities of rat tissue hexose monophosphate dehydrogenases in response to premature weaning and dietary restriction at mid-lactation

Summary The activities of the hexose monophosphate dehydrogenases increased in adipose tissue, remained unchanged in liver and decreased in mammary gland following the weaning of rats at mid-lactation (day 14). When dietary intake was restricted at mid-lactation, the activities of the hexose monophosphate dehydrogenases increased in adipose tissue, decreased in liver, but were unaltered in mammary gland. Premature weaning on day 14 postpartum resulted in maternal increases in both plasma insulin and glucose, which peaked at day 16. The plasma insulin levels decreased from day 14 to day 18 postpartum in the normal lactating rat, and a similar trend was observed for animals on a restricted dietary intake. Daily food consumption in the lactating rat decreased from 50 g to 20 g after premature weaning. The live weight of pups raised on dams given a restricted food intake from day 14 had decreased by day 17 postpartum, whereas an increase in daily live weight gain was recorded for the litters from the lactating controls. The results demonstrate that the activities of the hexose monophosphate dehydrogenases are regulated differentially between tissues of the lactating rat.