Offspring from mothers fed a 'junk food' diet in pregnancy and lactation exhibit exacerbated adiposity that is more pronounced in females

We have shown previously that a maternal junk food diet during pregnancy and lactation plays a role in predisposing offspring to obesity. Here we show that rat offspring born to mothers fed the same junk food diet rich in fat, sugar and salt develop exacerbated adiposity accompanied by raised circulating glucose, insulin, triglyceride and/or cholesterol by the end of adolescence (10 weeks postpartum) compared with offspring also given free access to junk food from weaning but whose mothers were exclusively fed a balanced chow diet in pregnancy and lactation. Results also showed that offspring from mothers fed the junk food diet in pregnancy and lactation, and which were then switched to a balanced chow diet from weaning, exhibited increased perirenal fat pad mass relative to body weight and adipocyte hypertrophy compared with offspring which were never exposed to the junk food diet. This study shows that the increased adiposity was more enhanced in female than male offspring and gene expression analyses showed raised insulin-like growth factor-1 (IGF-1), insulin receptor substrate (IRS)-1, vascular endothelial growth factor (VEGF)-A, peroxisome proliferator-activated receptor-γ (PPARγ), leptin, adiponectin, adipsin, lipoprotein lipase (LPL), Glut 1, Glut 3, but not Glut 4 mRNA expression in females fed the junk food diet throughout the study compared with females never given access to junk food. Changes in gene expression were not as marked in male offspring with only IRS-1, VEGF-A, Glut 4 and LPL being up-regulated in those fed the junk food diet throughout the study compared with males never given access to junk food. This study therefore shows that a maternal junk food diet promotes adiposity in offspring and the earlier onset of hyperglycemia, hyperinsulinemia and/or hyperlipidemia. Male and female offspring also display a different metabolic, cellular and molecular response to junk-food-diet-induced adiposity.     

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.     

AMP-activated protein kinase signalling pathways are down regulated and skeletal muscle development impaired in fetuses of obese, over-nourished sheep

Maternal obesity and over-nutrition give rise to both obstetric problems and neonatal morbidity. The objective of this study was to evaluate effects of maternal obesity and over-nutrition on signalling of the AMP-activated protein kinase (AMPK) pathway in fetal skeletal muscle in an obese pregnant sheep model. Non-pregnant ewes were assigned to a control group (Con, fed 100% of NRC nutrient recommendations, n = 7) or obesogenic group (OB, fed 150% of National Research Council (NRC) recommendations, n = 7) diet from 60 days before to 75 days after conception (term 150 days) when fetal semitendinosus skeletal muscle (St) was sampled. OB mothers developed severe obesity accompanied by higher maternal and fetal plasma glucose and insulin levels. In fetal St, activity of phosphoinositide-3 kinase (PI3K) associated with insulin receptor substrate-1 (IRS-1) was attenuated ( P < 0.05), in agreement with the increased phophorylation of IRS-1 at serine 1011. Phosphorylation of AMP-activated protein kinase (AMPK) at Thr 172, acetyl-CoA carboxylase at Ser 79, tuberous sclerosis 2 at Thr 1462 and eukaryotic translation initiation factor 4E-binding protein 1 at Thr 37/46 were reduced in OB compared to Con fetal St. No difference in energy status (AMP/ATP ratio) was observed. The expression of protein phosphatase 2C was increased in OB compared to Con fetal St. Plasma tumour necrosis factor α (TNFα) was increased in OB fetuses indicating an increased inflammatory state. Expression of peroxisome proliferator-activated receptor γ (PPARγ) was higher in OB St, indicating enhanced adipogenesis. The glutathione: glutathione disulphide ratio was also lower, showing increased oxidative stress in OB fetal St. In summary, we have demonstrated decreased signalling of the AMPK system in skeletal muscle of fetuses of OB mothers, which may play a role in altered muscle development and development of insulin resistance in the offspring.     

The effect of chronic protein malnutrition on trans-callosal evoked responses in the rat.

Studies were carried out on the trans-callosal evoked response in rats born of dams fed either a low (8%) or normal (25%) protein diet beginning 5 weeks prior to mating and throughout gestation and lactation. After weaning, pups were fed the same diets as their mothers. Bipolar (surface vs depth) stainless steel stimulating and recording electrodes were positioned at corresponding loci in the right and left sensorimotor cortices. Trans-callosal evoked responses were measured under urethane anesthesia using twice-threshold bipolar pulses of .1 msec duration at ages 13, 21, and 60-66 days. Evoked response latency was significantly greater in malnourished animals at 13 days of age, whereas at adulthood no latency differences were seen. Poststimulation excitability (15-100 msec range) was not significantly affected by the dietary treatment. These results are interpreted as corroborating previous reports on rats undernourished during development using sensory evoked potentials. By avoiding the use of extrinsic sensory stimulation, the present study demonstrates a dietary effect upon ontogeny of cortical evoked potentials independent of any possible effect on sensory receptor mechanisms.     

母鼠孕前营养过剩对子代小鼠生长发育影响

目的构建孕前营养过剩及超重小鼠模型,探讨孕前营养过剩对子代小鼠生长发育影响。方法 20只昆明种雌鼠随机分为对照组和实验组,分别给予标准饲料和高脂高糖饲料;两组单纯饲养4周后与雄鼠合笼,孕期继续上述饮食;产后均母乳喂养,产后3w断乳,哺乳期间母鼠仍按各自组别进食;监测单纯饲养期、孕期和哺乳期母鼠体重、血糖变化。两组子鼠断乳后一律以标准饲料喂养,监测子鼠出生至生后5w体重、身长和尾长发育。结果 1.母鼠体重和血糖变化：单纯饲养1周后开始实验组母鼠体重持续显著高于对照组（P〈0.05）;饲养1w和4w时,实验组母鼠血糖显著高于对照组（P〈0.05）。孕中、晚期实验组母鼠体重与对照组无显著差异（P〉0.05）。哺乳期两组母鼠体重、血糖均无显著差异（P〉0.05）。2.母乳喂养期子鼠发育：出生3天和7天,实验组子鼠体重显著高于对照组（P〈0.05）;整个母乳喂养期,实验组子鼠尾长显著长于对照组（P〈0.05）,两组子鼠身长无显著差异（P〉0.05）。3.自由采食期子鼠发育：整个自由采食期,实验组雌性子鼠体重显著高于对照组（P〈0.05）;出生35天,实验组雄性子鼠体重也显著高于对照组（P〈0.05）;整个自由采食期,实验组子鼠尾长均显著长于对照组（P〈0.05）,两组子鼠身长无显著差异（P〉0.05）。结论通过高脂高糖饲料可以建立孕前营养过剩及超重小鼠模型,母鼠孕前营养过剩导致子代小鼠出生体重增加以及成年早期肥胖,其对机体的深入影响及机制值得进一步研究。     

Pregnancy and lactation in the obese rat: Effects on maternal and pup weights

Lister hooded female rats, fed palatable high energy foods and chow, weighed significantly more than chow-fed control rats before mating. A smaller proportion of the obese rats became pregnant, and they lost more litters in lactation. When litters survived (7±1 pups), maternal weight changes differed between groups during lactation. The controls gained 6.2±3.2 g, whereas the obese rats lost variable amounts of weight despite the continued availability of the palatable diet. The rats that were heaviest at mating and parturition and which showed the largest non-fetal weight gains in pregnancy (i.e., the “large weight loss group”) lost 60.6±4.8 g, while less obese rats which showed similar non-fetal gains to controls (i.e., the “small weight loss group”) lost 24.6±3.2 g. Thus the weights of all groups converged and were similar after three weeks of lactation, but diverged again after weaning. During lactation the total energy intakes and amounts of protein consumed by the obese rats were significantly below those of controls, and total fat intake was significantly elevated. Although litter size and pup weights did not differ significantly at birth, pups of obese mothers weighed significantly less than those of controls at weaning. Maternal obesity in lactation appears to influence both body weight regulation and lactational performance.     

Protein restriction during fetal and neonatal development in the rat alters reproductive function and accelerates reproductive ageing in female progeny

Recent studies demonstrate long-term programming of function of specific organ systems resulting from suboptimal environments during fetal life and development up to weaning. Nutrient restriction during pregnancy and lactation impairs overall fetal growth and development. We determined the effects of maternal protein restriction (MPR; 50% normal protein intake) during fetal development and/or lactation in rats on the function and ageing of the reproductive system of female progeny. Rats were fed either a control 20% casein diet (C) or a restricted diet (R) of 10% casein during pregnancy. After delivery mothers received either C or R diet until weaning to provide four groups, CC, RR, CR and RC. We report data on female offspring only. After weaning pups were fed the C diet. MPR increased maternal progesterone, corticosterone, oestradiol and testosterone concentrations at 19 days gestation. Reproductive and somatic phenotype was altered as pup birth weight was decreased, and ano-genital distance was increased by MPR. Pup corticosterone was decreased at 2 days postnatal (PN) life. Vaginal opening and timing of the first oestrus were delayed in RR and CR and these differences were not related to body weight. At 21 days PN oestradiol in RR and CR and progesterone in RR were reduced; at 70 days PN luteinizing hormone (LH) in all restricted groups was reduced in dioestrus while follicle stimulating hormone (FSH) was unchanged. Cycle length increased between 140 days and 1 year in RR and CR but remained unchanged in CC, providing evidence of premature ageing of reproductive function. Fertility rates declined over the same period in the three experimental groups but not CC. MPR in one of the two experimental periods, either pregnancy or lactation, resulted in decreased pup survival compared with CC and RR. These data show that MPR results in delayed sexual maturation and premature ageing of reproductive function.     

Diet choice exaggerates food hoarding, intake and pup survival across reproduction

Siberian hamsters increase food intake and hoarding during pregnancy and lactation, perhaps to compensate for large decreases in body fat (approximately 50%). We tested the effects of diet choice on these responses in pregnant, lactating and virgin hamsters housed in a simulated burrow system. Hamsters were offered pellet chow (PC) or a choice of sunflower seeds (SS), rabbit chow (RC) and PC. Pregnant or lactating PC-fed hamsters had increased food intake and hoard size compared with virgins, effects exaggerated by diet self-selection. The pregnancy-induced increases and lactation-induced decreases in body mass were enhanced and diminished by diet self-selection, respectively. Pregnant self-selecting hamsters ate relatively more carbohydrate and less fat and hoarded less carbohydrate and more fat than their virgin counterparts (protein not affected). Lactating and virgin self-selecting hamsters both ate and hoarded relatively more carbohydrate than protein or fat compared with PC-fed hamsters but were not different from each other. Litter and pup sizes were similar at birth, but pups from self-selecting mothers had decreased lipid content (50%) compared with pups from PC-fed mothers, whereas at weaning they were heavier but not fatter. Only lactating PC-fed mothers cannibalized their pups (approximately 60% eaten, 8/10 litters). The pregnancy-induced increased eating and hoarding of carbohydrate may have helped meet immediate energy needs sparing dwindling lipid reserves, whereas the decreased fetal lipid investment may have helped conserve energy in anticipation of the increased demands of lactation. The diet-induced exaggerated caloric intake and food hoard size of lactating hamsters may have promoted pup growth and survival.     

Early exposure to sugars influences the sugar preference of the adult rat

Female rats were maintained on either a High Sucrose or High Glucose diet during gestation and lactation. Their pups were continued on the same diet as their dam until they were 42 days of age; thereafter all animals were maintained on laboratory chow. From 21-84 days of age, each rat was given a weekly two-choice preference test between the High Sucrose and High Glucose diets. Rats that were fed the High Sucrose diet throughout their early development had heavier body weights and a greater preference for the High Sucrose diet beginning on Day 63 than did the rats that were fed the High Glucose diet. Rats fed the High Glucose diet demonstrated a greater preference for the High Glucose diet during adulthood. These data indicate that early dietary experience can modify the rat's subsequent preference for sugars.     

Lack of IgA antibody response in secretions of rat dams during long-term ovalbumin feeding. Induction of systemic tolerance in pups but not in adult rats

Antigen uptake, serum and secretory immune response was studied in rat dams fed pellets substituted with ovalbumin during three consecutive pregnancies and lactation periods. The concentration of ovalbumin was somewhat higher in milk than in serum, and both serum and milk concentrations showed a parallel decrease with feeding time. IgA antibodies did not develop in the milk during the 7-month feeding period and no antibody response could be detected in saliva or bile. By the time of the first lactation about half of the dams had developed low titres of IgG antibodies in serum and milk and the number of IgG responders, as well as the mean antibody titre, increased with each lactation. Also when injected directly into the Peyer's patches ovalbumin induced solely IgG antibodies in the milk, while immunization with ferritin in addition resulted in both IgA and IgM antibodies in the milk against ferritin. The presence or absence of immunological tolerance to ovalbumin was examined in three groups of rats: (1) dams which had been fed ovalbumin-substituted pellets for one pregnancy and the first 14 days of the lactation period, i.e. for approximately 5 weeks altogether; (2) pups that were born by and kept together with these mothers, and (3) pups that were born by and kept together with mothers that were fed ovalbumin-substituted pellets during the pregnancy and until weaning at day 21 (altogether for 6 weeks). The rat dams in group 1 were not tolerant to a subcutaneous injection of ovalbumin 4 weeks after the termination of feeding with ovalbumin-substituted food.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of diet and obesity on body weight regulation during pregnancy and lactation in the rat

The effects of obesity level and cafeteria feeding were studied in rats during pregnancy and lactation. The non-fetal weight gain in pregnancy was three times greater with the cafeteria diet than with chow, indicating that fat deposition is not regulated at an optimal level during pregnancy. There was a strong negative correlation between postpartum weight and weight change during lactation. Obese rats were finicky in that their weight changes in lactation were exaggerated when the diet was changed between pregnancy and lactation. Pup growth rate was proportional to maternal energy intake but in this experiment not related to maternal protein, fat or carbohydrate intake. In obese rats switched to chow, intake was inadequate for normal pup growth. Thus, the weight gains in pregnancy are not regulated at a set level, and the weight change in lactation appears to compensate for the weight gain in pregnancy.     

Effects of high fat,protein supplemented diets on maternal behavior in rats

Female albino rats were maintained on either chow, a 25% fat, protein supplemented diet or a 45% fat, protein supplemented diet during breeding, gestation and lactation. Materanal behavior was assessed using observational techniques. Maternal bodyweight of the females on the high fat diets was not different from females on chow. Reproductive success, as indicated by pregnancy and pup survival, was reduced in the females on the 45% fat diet. However, unlike offspring of obese dams, pup growth was enhanced in most of the offspring of the dams on the high fat, protein supplemented diets. The dams on these diets showed more postural nursing, less non-postural nursing, more pup grooming and were observed more frequently with a majority of their pups. These dietary differences in maternal behavior did not appear to be necessarily due to differences in the body weight of the pups.     

Maternal malnutrition in the rat: Effects on food intake and body weight

The effects of dietary protein level on food intake and body weight were examined in adult female rats during a 35-day pre-mating period and during gestation and lactation. During the pre-mating period, no differences in daily food intake were observed among rats fed a 6% casein, 8% casein or 25% casein diet. However, during this period, rats fed the 6% casein diet gained significantly less weight than those with ad lib access to the 8% or 25% casein diets or than rats pair-fed the 25% casein diet in amounts equivalent to that consumed by rats in the 6% or 8% casein groups. Additionally, rats fed the 6% casein diet displayed decreased efficiency of energy utilization, calculated as weight gain per 100 kilocalories consumed, relative to rats fed the 8% or 25% casein diets. No differences in food intake were observed among the groups during gestation. However, rats fed the 6% casein diet gained less weight than rats fed the 8% or 25% casein diets. During lactation rats fed either the 6% or 8% casein diet consumed significantly less food than animals given the 25% casein diet ad lib. During the second week of lactation, rats receiving ad lib access to the 25% casein diet gained weight while those receiving the 6% or 8% casein diets continued to lose weight. At parturition, body weights of pups did not differ as a function of dietary condition. However, by day 12 of life, pups whose dams had ad lib access to the 25% casein diet weighed significantly more than pups whose dams consumed the 6% or 8% casein diet or whose dams were pair-fed the 25% casein diet in amounts equivalent to those consumed by rats fed the 6% or 8% casein diet.     

Maternal stress and high-fat diet effect on maternal behavior, milk composition, and pup ingestive behavior

Chronic variable prenatal stress or maternal high-fat diet results in offspring that are significantly heavier by the end of the first postnatal week with increased adiposity by weaning. It is unclear, however, what role maternal care and diet play in the ontogenesis of this phenotype and what contributions come from differences already established in the rat pups. In the present studies, we examined maternal behavior and milk composition as well as offspring ingestive behavior. Our aim was to better understand the development of the obese phenotype in offspring from dams subjected to prenatal stress and/or fed a high-fat (HF) diet during gestation and lactation. We found that dams maintained on a HF diet through gestation and lactation spent significantly more time nursing their pups during the first postnatal week. In addition, offspring of prenatal stress dams consumed more milk at postnatal day (PND) 3 and offspring of HF dams consume more milk on PND 7 in an independent ingestion test. Milk from HF dams showed a significant increase in fat content from PND 10-21. Together these results suggest that gestational dietary or stress manipulations can alter the rat offspring's developmental environment, evidence of which is apparent by PND 3. Alterations in maternal care, milk composition, and pup consumption during the early postnatal period may contribute to long-term changes in body weight and adiposity induced by maternal prenatal stress or high-fat diet.     

Lack of diet-induced thermogenesis following lesions of paraventricular nucleus in rats

The effects of electrolytic lesions in the hypothalamus paraventricular nucleus were studied in adult male and female Sprague-Dawley rats, fed different diets, consisting of either palatable human food plus chow (cafeteria diet) or chow alone. The results showed that both cafeteria diet and lesions induced an increase in energy intake and weight gain in rats of both sexes. Oxygen consumption rate and colonic temperature were significantly decreased by lesions, while cafeteria diet increased the same parameters only in intact animals. The lesion decreased weight, protein and DNA, and temperature of brown adipose tissue, while cafeteria diet increased the values considered in brown adipose tissue of sham-injured rats, but not in lesioned animals. The response to norepinephrine administration was significantly greater in intact rats and those fed cafeteria diet. The results suggest that the larger body weight gain observed in lesioned rats, particularly evident in rats fed cafeteria diet, is partly due to the disappearance of diet-induced thermogenesis that depends on the reduced mass and functional activity of brown adipose tissue.     

The impact of maternal cafeteria diet on anxiety-related behaviour and exploration in the offspring

Contemporary trends in obesity mean that research into whether unbalanced diets could impact on behavioural traits became increasingly important. The timing of exposure to obesity is particularly important, as sensitive periods during development have been identified where dietary extremes play a critical role in determining adult risk of physiological dysfunction. To this end, female Wistar rats were fed on chow or cafeteria diet (CD) for 8 weeks from weaning until mating. Half of the mated animals within each group were crossed-over to the alternative diet. This generated four treatment groups, differing in their pre-gestational and gestational diets. After birth, offspring of dams from each of the 4 pregnancy groups were further divided into groups, either being fed chow or CD throughout lactation. Anxiety-related behaviour and exploration in the offspring were tested in the Elevated Plus Maze (EMP) and the Open Field (OF) at 10 weeks of age. Maternal obesity significantly reduced the EPM locomotor activity in male and female offspring and grooming in males. Lactational CD had an anxiolytic effect in male offspring as shown in the EPM (increased entries into and more time on open arms) and the OF (shorter latency to enter the centre). In both sexes, lactational CD reduced grooming upon exposure to the EPM and the OF. Post mortem analysis revealed a stimulant effect of lactational CD on adipose tissue growth. The present study demonstrates that pre-gestational, gestational and lactational maternal CD programme behaviour in the offspring with lactational CD reducing anxiety in the male offspring.     

Adolescent pregnancy and growth of progeny in rats

The relationship between very young adolescent mothers and their progeny was studied in terms of fetal development and pup growth. The mothers used in this study had just attained puberty and were still growing; their body weight was about half that of normal full-grown adult females. Still, they were able to conceive and to maintain gestation but growth and skeletal development of their fetuses was significantly retarded. Adolescent dams took in more food during gestation, and about 60% of the intake was used to meet their own growth and development need rather than that of their progeny. During lactation, adolescent dams took in about the same amount of food as did the control, but the pups they were suckling gained significantly less weight than did pups suckled by the control. Retardation of growth and development during gestation, and the continued retardation during lactation, can best be explained by an overall nutritional competition between adolescent dams and their offspring.     

The effects of Cannabis sativa L. seed (hemp seed) on reproductive and neurobehavioral end points in rats

This study determined the effects of maternal dietary intake of hemp seed on reproductive and neurobehavioral end points of Wistar rats. Time-mated rats were fed 100% hemp seed (n = 15), 50% hemp seed (n = 15) or basal diet (n = 15) once a day. The amount of food made available was based on control feed consumption records. All dams remained on their respective diets from premating (14 days) throughout gestation and lactation. After weaning, all pups were given their maternal diet until puberty. Mating and delivery weights of dams in all groups did not show significant changes. Number of pregnancies, number and post-natal survival rate of total rat pups, litter size and milk yield were lower in the group that received 100% hemp seed. Offspring that received 50% hemp seed diet expressed reproductive and neurobehavioral end points from a modified Fox battery earlier than rats on 100% hemp seed or basal diet, except acoustic startle results where no differences appeared. In conclusion, this study shows that hemp seed supplementation does not improve the reproductive and neurobehavioral performances of rats. Pregnant women and nursing mothers should be cautious about the using of Cannabis sativa L. byproducts in their diets.     

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.