Body weight and brown fat activity in hyperphagic cafeteria-fed female rats and their offspring

Presenting pregnant rats with a varied choice of human food items (a cafeteria diet) caused a slight reduction in total protein intake and significant increases in energy intake (32%) and weight gain compared to pregnant females fed stock diet (controls). Cafeteria-fed mothers gave birth to the same number and weight of pups as controls, and these grew normally, but were fatter at weaning than control pups. Cafeteria-fed dams lost more weight than controls during lactation, in spite of sustained hyperphagia, and body fat and energy was the same as controls at 21 days post-partum. Brown adipose tissue protein content and thermogenic activity (assessed from mitochondrial purine nucleotide binding) were both elevated in cafeteria-fed mothers when compared to controls at 21 days post-partum, but brown fat activity in their offspring at weaning did not differ between treatments, although tissue protein content was depressed in the pups of cafeteria-fed dams.     

Measurement of milk yield in the lactating rat from pup weight and weight gain

A new method was developed that enables milk yield to be estimated from pup weight and pup weight gain in well-nourished rats. Daily milk yield, body weight, and daily weight gain were measured over 4-5-day periods in 38 suckling pups aged 3-13 days postpartum. Each 24-h period was divided into consecutive 6-h cycles, during which dams and pups were separated for 4 h and then reunited for 2-h suckling intervals. Daily milk yield per pup was calculated from pup weight gain during the four suckling intervals for each 24-h period, and corrected for insensible weight loss of the pups. The following equation, relating pup milk yield to pup weight and weight gain, was obtained by stepwise forward multiple regression analysis: yield = 0.0322 + 0.0667 (weight) + 0.877 (gain); where yield is daily yield per pup (g/pup/day), weight is pup weight (g), and gain is pup weight gain per day (g/day) (n = 174; F = 552.3; p less than 0.001; r2 = 0.866). Per litter milk yield can be obtained by multiplying per pup yield by litter size. Using this equation, dams fed a stock diet and nursing eight pups were estimated to have produced 29.5 ml of milk on day 10 of lactation. This value is similar to yields measured by more laborious methods. SEs of yield estimates calculated with this method represent 1-3% of predicted yield values. The new method gives useful estimates of rat milk yield during the first 2 weeks of lactation from measurements that are more easily obtained than is the case with other methods.     

Ontogenic changes in serum immunoglobulins and C3 in vitamin-D deficient and malnourished rats

In both protein energy malnutrition and vitamin D deficiency, defects in some immunological functions have been noted, but the effects on complement and immunoglobulin concentrations have not been evaluated. We assessed the effects of malnutrition and vitamin D deficiency on immunoglobulins and C3 in rats in early postnatal life during weaning and early adulthood using the rocket immunoelectrophoresis technique. In well-nourished rats, the serum levels of IgG increased from 88.5 +/- 10.2 mg/dl in the newborn period to 883.4 +/- 104.8 mg/dl at weaning (day 19). The adult levels, 1,325.9 +/- 60.8 mg/dl, were attained by 35 days of age. Serum IgA was not detectable by our method until 20 days of age (1.1 +/- 0.2 mg/dl) and reached adult levels (13.4 +/- 3.2 mg/dl) by day 35. IgM was detectable in the serum of pups at 5 days of age (0.4 +/- 0.07 mg/dl), increased to 27.5 +/- 6.9 mg/dl at weaning and approached adult levels (93.7 +/- 9.9 mg/dl) at day 35. C3 levels at birth were only 36% of adult levels and did not change during the suckling period. They then increased to levels comparable to those of adults at the age of 35 days. Serum immunoglobulins and C3 in malnourished rats were not significantly different from age-matched control pups. In pups born to dams fed a vitamin-D-deficient diet from 3 weeks of age, only the serum IgG and C3 levels were significantly lower than those of normal pups at day 1 (IgG level: 65.2 +/- 6.1 vs. 88.5 +/- 10.2 mg/dl; C3 level: 20.3 +/- 6.9 vs. 36.2 +/- 3.1% of an adult level; p less than 0.005). Thus the increased susceptibility of malnourished young animals to infection does not appear to be related to a lowering of serum immunoglobulin and complement concentrations.     

Neonatal hypoxia in the rat: effects on exocrine pancreatic development

BACKGROUND: Glucocorticoids profoundly affect pancreatic development during the suckling period. Increases in circulating glucocorticoids during exposure to hypoxia may alter the normal pattern of pancreatic enzyme development. METHODS: Rats were exposed to hypoxia from birth to 7 days (suckling) or from 28 to 35 days of age (weaned at day 21). RESULTS: Hypoxia in neonatal rats (0-7 days) led to decreased pancreatic weight, and trypsin, lipase, and amylase activity compared with normoxic controls. In contrast, rats exposed to hypoxia from 28 to 35 days of age had decreased lipase activity but no change in other pancreatic parameters. Two weeks after hypoxia (0-7 days) pups were returned to normoxia, and their body weights remained smaller than the age-matched, previously normoxic controls. Pancreatic enzyme activities were decreased in the group recovering from hypoxia compared with controls. Recovery of enzyme activities was observed 3 weeks after hypoxic rats were returned to normoxia. Normoxic pups were given dexamethasone to simulate the hyperglucocorticoid state in hypoxia at 7-day olds. Dexamethasone administration led to decreased body weight, but increased pancreatic weight and enzyme activity compared with normoxic, age-matched controls. CONCLUSIONS: Hypoxia in newborn rats delays the maturation of pancreatic exocrine enzymes. The mechanism is not related to increased serum glucocorticoids.     

Effect of chronic caffeine intake on myocardial function during early growth

The purpose of these studies was to evaluate the effects of chronic caffeine ingestion on the myocardium during fetal and neonatal growth and development. The isolated perfused working heart preparation was used to evaluate cardiac function. During gestation and lactation, one group of dams consumed a caffeine supplemented diet (10 mg/kg/day). Their offspring were sacrificed and the hearts analyzed 50 days after birth. We found that the intake of caffeine by the dams resulted in significant increases in the offspring's coronary flow, peak systolic pressure, and myocardial work. A second group of dams ingested a diet containing caffeine (10 mg/kg/day) during lactation only. Their pups continued to consume the caffeine diet until 50 days. Pup hearts exhibited significant reductions in cardiac output, stroke volume, pressure development, myocardial work, and external efficiency when compared to controls. Caffeine did not affect body or heart weight or adipose size or number in these experiments. Thus, continued caffeine consumption following birth may alter cardiac performance of the offspring.     

Effects of maternal hypocaloric diet feeding on neonatal rat brown adipose tissue

Hypocaloric diet (control diet diluted 1:1 with cellulose) feeding during pregnancy caused a reduction in the body weight of rat pups at birth whereas the main parameters of brown adipose tissue composition and thermogenic activity were unaffected. When prenatally underfed rat pups were nursed by untreated dams eating control diet during lactation, early (day 4 of life) and late (day 13 of life) neonatal body weight was rehabilitated and brown adipose tissue remained essentially unchanged. When prenatally underfed rat pups were nursed by dams that were fed with the hypocaloric diet during lactation, neonatal body weight continued lower at the two mentioned days of life and the overall thermogenic capacity of brown fat (GDP binding/g body weight) was substantially depressed. The reduction of the brown fat thermogenic capacity in these pups is mainly due to a hypotrophy of the mitochondrial component of the tissue as indicated by the lowered cytochrome oxidase activity. Results indicate that mild maternal underfeeding during lactation may depress brown adipose tissue thermogenic function in neonates whereas similar hypocaloric intakes during pregnancy did not alter brown fat thermogenic capacity.     

Effect of epidermal growth factor and artificial feeding in suckling rats

To evaluate the effects of epidermal growth factor (EGF) in dietary milk, a new method of delivering an artificial (EGF-deficient) formula was developed using 42 rat pups, 1-14 days of age. In a second study the effect of EGF was evaluated in suckling rats from 3-11 days of age: group 1, mother-fed; group 2, mother-fed plus daily injections of EGF (0.1 micrograms/g body weight); group 3, artificial milk fed with added EGF (62 ng/ml); and group 4, artificial milk fed without EGF. Each group consists of nine rats. In group 2 there was premature eye opening and tooth eruption and a significant reduction in body weight and weight of liver, kidney, thyroid, and thymus but an increase in length of the intestine and weights of stomach, pancreas, lung, and adrenal (p less than 0.04), when compared to group 1. Both groups 3 and 4 showed premature tooth eruption and eye opening, and their body weights and most organ weights were similar to group 2; exceptions were a smaller stomach, thyroid, thymus, lung, and adrenal, which were similar to those in group 1. In addition, intestinal length in groups 3 and 4 were similar to the mother-fed EGF-treated pups (group 2). There was no difference in intestinal length between the artificially fed pups, whether or not they received oral EGF. These findings demonstrate a new and effective technique of artificial feeding and suggest that the increase in intestinal length caused by injections of EGF (0.1 micrograms/g body weight) can also be induced by feeding an artificial milk with or without physiologic levels of EGF.     

Saccharin- or quinine-induced changes in the rat pups following prolonged ingestion by the dam

Effects presumably induced by a chronic free ingestion of saccharin (0.40 mg/ml) or of quinine (0.25 mg/ml) by female rats during the pregestative, gestative and lactating periods were investigated in the ensuing progeny. Preweaned pups were studied from birth up to weaning (21 days of age) by means of selected gross behavioral tests. The saccharin litters were mainly characterized by a slowering in the body growth evolution. The quinine pups demonstrate several physical anomalies: (1) congenital malformations in 5% of the animals; (2) a significantly reduced birth weight followed by a persistent growth retardation, and (3) a significant delay in the teeth eruption (1.6 and 2.6 days) and in the eye openings (1.6 days). In comparison to the untreated offspring, the saccharin pups showed minor effects whereas quinine-exposed rats were clearly impaired in several features of the postnatal physical development. Therefore, the addition of the sweetener to morphine solution may be convenient for the voluntary oral consumption of the narcotic. Conversely, quinine, used to habituate animals to drinking bitter solutions, has to be rejected in this narcotization procedure as being a harmful agent to the growing rat.     

Effects of oral caffeine intubation on bones in protein-energy malnourished newborn rats

Lactating dams with 8 suckling pups were fed either a 6% or a 20% protein diet from the birth of the pups to day 15. The pups were divided into caffeine and noncaffeine groups. Every other day between days 3 and 13, pups were either intubated with caffeine (1 mg/100 mg) dissolved in 0.1 ml physiological saline solution, or 0.1 ml saline solution as a control. On day 15, mandible and long bone weights, DNA, protein and calcium contents, collagen synthesis and 45Ca uptake in these bones of the pups were studied. Nutritional factors exercised consistent effects on all the studied parameters, but there was no difference in effects attributable to caffeine intubation, except the increased collagen synthesis in the long bones of the group with 6% protein diet with caffeine as compared to noncaffeine members of the same dietary group. We concluded that the direct administration of a relatively small amount of caffeine to newborns causes minor effects on bone development under certain nutritional conditions.     

Impact of maternal food restriction on cold-induced thermogenesis in the offspring

Food restriction imposed during pregnancy usually leads to many alterations in the development of the conceptus. Some of these alterations can be reverted after birth by adequate nutritional rehabilitation, while there are others which are permanent. The aim of this article is to study the influence of maternal food restriction on offspring thermoregulation. Offspring of dams with food restriction during pregnancy (50%) were fed ad libitum after weaning. Rectal temperature was measured every 15 days from weaning to the 90th day of life. From the 60th to the 90th day the animals were either acclimated at 25 or 5 degrees C. On the 90th day the animals were killed and their carcasses were processed for energy balance analysis and body composition determination. The results showed that animals from food-restricted mothers were not able to maintain body temperature for a longer period of time than the pups from control dams. Energy balance parameters and body composition did not show significant differences between rats from control and food-restriction mothers at the same environmental temperature. Thus, the results suggest that intrauterine food restriction may delay the development of the hypothalamus-thyroid axis which, in turn, may affect brown adipose tissue development leading to inefficient thermoregulation during neonatal life.     

Effects of maternal nicotine exposure during lactation on breast-fed rat pups

BACKGROUND: Nicotine is known to be associated with adverse effects in infants and children. It is concentrated in breast milk and is absorbed by the infant. The aim of this study was to investigate the effects on breast-fed rat pups of maternal nicotine exposure during lactation. METHODS: In the experimental group (n = 6), nicotine was given to lactating dams (2 mg/kg/day) after delivery and continued for 10 days during lactation. Control animals (n = 4) received saline for the same duration. The suckling rats were weighed and killed on postnatal day 10, and samples were taken from the lung, liver, kidney, spleen and small intestine for histopathological examination. Superoxide dismutase (SOD), catalase (CAT) activities and malondialdehyde (MDA) levels were measured in the liver of the dam and the offspring. RESULTS: Histopathological changes in the liver of the nicotine-exposed group showed portal inflammatory infiltrate, ballooning degeneration of hepatocytes, and focal necrosis in the parenchyma. Thickening of alveolar walls because of interstitial inflammation was noted in the lungs. Histopathological examination of kidney, spleen and small intestine tissue did not reveal any abnormality. In the experimental group, SOD and CAT activities were significantly decreased (p <0.001) but MDA levels were significantly increased (p <0.001) compared with the control group. CONCLUSION: These results indicate that maternal nicotine exposure induces oxidative stress and causes detrimental histopathological changes in the lung and liver of lactating offspring.     

Intestinal glucose metabolism during development. II. The role of glucocorticoids and weaning

Prolonged suckling, until 25 postnatal days, delays the increase in jejunal oxidation of glucose both to lactate and to CO2 that occurs after artificial weaning at 20 days of age. The cortisone-mediated increase in intestinal sucrase activity which normally occurs by 20 days is not effected by prolonged suckling. Following precocious weaning at 16 days, the rate of jejunal glucose oxidation to lactate and to CO2 increases, over a 48-h period, to adult rates. Exogenous cortisone treatment at 10-13 postnatal days, before the endogenous steroid burst, does not change the rate of glucose oxidation in suckling animals. After weaning, both at 20 days of age and precociously at 16 days, the rate of glucose oxidation to lactate and to CO2 increases within 24 h in those animals who received early steroid treatment, in comparison to 48-72 h in untreated controls. After prolonged suckling until 25 days, there is no effect of early steroid treatment. We conclude that neither endogenous glucocorticoid secretion nor exogenous cortisone treatment alters the rate of glucose oxidation in jejunum of suckling animals despite the induction of jejunal sucrase activity. After early cortisone treatment, glucose oxidation increases within 24 h of normal of precocious weaning.     

Effects of suckling and the postsuckling fast on weights of the body and internal organs of harp and hooded seal pups

The weights of harp seal pups quadruple during 13 days of suckling while hooded seal pups double in weight in a lactation period of just 4 days. Pups of both species then fast for a month or longer. As a first measure of tissue responses to this 'feast and famine' pattern, we weighted the body, sculp (blubber and attached skin), core (carcass including viscera) and major internal organs of seal pups at birth, at the end of suckling, and at the end of the fast. When expressed as a percentage of body weight, the weights of the internal organs of newborn harp and hooded seals were within the range reported for newborn land mammals. During suckling, harp and hooded seals gained 2.3 and 6.5 kg/day body weight, respectively, but a large part (64-73%) of this gain was blubber and skin rather than core. Even though pups were ingesting great quantities of fat, their digestive organs (stomach, small and large intestines, pancreas) were neither particularly large at birth nor did these organs gain in weight or length unusually rapidly. Most organs increased in weight in proportion to the increase in core weight, but the liver and spleen increased proportionately more than the core, and the stomach, heart and kidneys increased proportionately less. At the end of suckling, sculp accounted for more than half of the body weight in both species. The subsequent 4-week fast resulted in weight loss from both the sculp and core, and the liver and spleen decreased in weight by about 70%. The net effect of sequential suckling and fasting was particularly striking in the hooded seal pup, which has a lighter core, heart, liver and spleen at 1 month postpartum than at birth. These data illustrate a remarkable cycle of nutrient deposition and depletion which is undoubtedly central to the survival of young seals in the harsh pack-ice environment.     

Dose-related and other effects of maternal cimetidine pretreatment during lactation on drug metabolism in mouse dams and pups

The effects of maternal cimetidine pretreatment at different dose levels during lactation, on drug metabolism, were investigated in mouse dams and recently weaned pups. Aminopyrine N-demethylase, aniline hydroxylase and pentobarbitone metabolism were inhibited in both dams and pups in a dose-dependent manner (15, 25 and 50 mg/kg/day, i.p.). Pretreatment at a dose level of 50 mg/kg/day resulted in comparable levels of inhibition of drug metabolism in dams and female pups while male pups were less affected. Of the three indices studied, aniline hydroxylase was the least influenced by cimetidine pretreatment. Thus, the effects of maternal cimetidine pretreatment on drug metabolism in the nursing pair varied with the dose, sex and substrate. The possible implications of these results for man are discussed.     

Pregnancy outcome in the Psammomys obesus gerbil on low- and high-energy diets

INTRODUCTION: Diabetes mellitus (DM) during pregnancy is associated with an increased risk for poor reproduction and a high rate of congenital malformations. The gerbil Psammomys obesus is a unique model for nutritionally induced Type 2 DM (T2DM) that enabled us to study the outcome of uncontrolled T2DM during pregnancy. METHODS: Female Psammomys on low-energy (LE) or high energy (HE) diet were studied. The blood glucose levels and weights of pregnant animals were determined. The offspring from the different groups were followed-up to weaning. RESULTS: Most of the HE-diet animals were diabetic (77%). There were no differences in the pregnancy rates in animals on both diets (32.7% in HE vs. 38.3% in LE). Pregnancy of the HE-diet group was longer than the LE-diet group (26.7 vs. 26.1 days), and litter average was reduced (2.7 vs. 3.0). At birth, the offspring of the HE-diet dams weighed less (5.2 vs. 7.2 g) and had smaller crown rump length (4.0 vs. 4.6 cm) These offspring also presented a 1-3 days delay in neuro-developmental parameters (first turn over, hair appearance, eye-opening and response to noise). However, from the fourth week of life they became diabetic, and from the third week they weighed more than the LE offspring. CONCLUSION: HE-diet caused diabetes, maternal complications and altered reproduction in Psammomys animals. The offspring of diabetic Psammomys presented birth weight and length changes as well as developmental delay.     

Perinatal feedings adversely affect lipogenic activities but not glucose handling in adult rats

The long-term effects of early under- and overfeeding on glucose metabolism and fat cell lipogenesis were studied. Newborn rats were reared in litter sizes of four, 10, and 16 pups. The amount of milk intake per pup varied inversely with litter sizes. A subgroup of pups from each group was studied at age 20 d, whereas another subgroup was weaned to an ad libitum feeding of standard rat chow and studied at 12 wk of age. There were no differences among groups in food intake on the basis of per gram body weight. Overfeeding during suckling resulted in fatter rats at weaning and in the adults. The higher fat contents in the adipose tissues and carcasses were associated with higher fatty acid synthase and lipogenic activities in the adipose tissues at weaning and 12 wk of age. Differences in plasma insulin and glucose levels among groups were observed only in the 20-d-old rats: basal insulin and glucose levels and 30-min postglucose insulin levels were highest in the overnourished and lowest in the undernourished rats. However, by 12 wk of age, there were no significant differences among groups in their basal insulin and glucose levels and after an oral dose of glucose. Our results suggest that overfeeding or underfeeding during the suckling period affects the glucose-insulin axis only temporarily and not permanently, but early overfeeding permanently enhances fatty acid synthase and lipogenic activities in adipose tissues, resulting in fatter adult rats.     

Brain beta-hydroxybutyrate utilization in neonatal hypothyroidism in rats

The in vitro and in vivo utilization of 14C-beta-hydroxybutyrate (BOHB) by the brain in neonatal hypothyroidism was studied in rat pups made hypothyroid by feeding dams a diet containing 0.02% propylthiouracil during pregnancy and lactation. In the in vitro studies, the oxidation of BOHB to CO2 was lower at 14 and 21 days of age in hypothyroid pups than in pair-fed controls but higher at 35 days. The incorporation of BOHB into brain lipid was significantly higher in hypothyroid pups at 14, 21 and 35 days. In contrast, in the in vivo studies, incorporation of BOHB into lipid was significantly lower in hypothyroid pups at 14 and 21 days. These results suggest that hypothyroid pups may have a normal or increased capability to use BOHB for lipid synthesis, but were unable to achieve normal rates of utilization in vivo, possibly due to a decreased substrate availability. These findings may have implications for the decreased brain lipid content characteristic of neonatal hypothyroidism.     

Prenatal exposure to ethanol in rats: effects on postnatal maturation of the small intestine and liver.

To examine the effects of prenatal exposure to ethanol on postnatal development of small intestinal and liver functions, female rats were accustomed to increasing amounts of ethanol (10 to 25%, vol/vol) in tap water for 1 mo. During pregnancy, ethanol-fed dams had higher daily caloric intake and similar weight gain compared with controls. In ethanol offspring, neonatal mortality was 28.9% compared to 0% in controls. Although ethanol had been withdrawn at birth, pups issued from ethanol-treated mothers showed at 5 and 10 d postpartum decreased values of body weight, jejunal and ileal weights, and intestinal DNA concentration per unit of length, as well as lower specific and total activities in lactase and maltase, compared with controls. DNA synthesis rates, measured by the incorporation of [3H]thymidine into mucosal DNA, were also significantly (-20 to -34%, p < 0.01) depressed in the jejunum and ileum of ethanol pups at 5 and 10 d of age. All these parameters returned to control levels by d 15 postpartum. Electron microscopy of jejunal mucosal samples at 5, 10, and 15 d of age revealed that ethanol pups differed from controls by a fetal-like immature aspect of the enterocytes, which persisted up to d 15. The ontogenic upsurge in sucrase and the decline in lactase occurred at weaning with the same chronology in both groups, but the level reached by sucrase activity was about 50% lower in alcohol offspring than in controls. Except for moderate steatosis, the ultrastructure of hepatocytes was unaltered in sucklings.(ABSTRACT TRUNCATED AT 250 WORDS)     

Maternal dietary n‐6/n‐3 fatty acid ratio affects type 1 diabetes development in the offspring of non‐obese diabetic mice

Environment factors, including maternal or infant dietary nutrition have been reported to have an influence on the pathogenesis of type 1 diabetes. In the present study, to investigate the effect of maternal or post‐weaning offspring's nutrition, in particular the essential fatty acid ratio (n‐6/n‐3) on the development of type 1 diabetes, we prepared two kinds of chows with n‐6/n‐3 ratios of 3.0 (L) and 14.5 (H), and provided them to mothers of non‐obese diabetic (NOD) mice during gestation and lactation and to the offspring after weaning. The n‐6/n‐3 ratios in breast milk and erythrocyte membrane of NOD offspring became nearly the same with that of the maternal diet at 2 weeks after birth. In the L chow‐fed offspring from L chow‐fed mother (LLL), levels of insulitis were higher than those in the H chow‐fed offspring from H chow‐fed mother (HHH) at 4 weeks of age, while the levels in the LLL offspring became lower than those in the HHH after 6 weeks. Early insulin autoantibody expressions were found from 2 to 6 weeks in the HHH offspring, but not in the LLL. The LLL offspring exhibited strong suppression of overt diabetes development in regard to the onset and accumulated incidence of diabetes compared to the HHH. The study with combined L and H chows during gestation, lactation in mother and in post‐weaning offspring revealed that only the LLH chow significantly suppressed the development of diabetes with similar kinetics to LLL chow, although the other combinations may delay the onset of diabetes. The present findings suggest that n‐6/n‐3 ratio of the maternal diet during gestation and lactation rather than that of offspring after weaning strongly affects the development of overt diabetes in NOD mice.