Impact of Diet Composition in Adult Offspring is Dependent on Maternal Diet during Pregnancy and Lactation in Rats.

The Thrifty Phenotype Hypothesis proposes that the fetus takes cues from the maternal environment to predict its postnatal environment. A mismatch between the predicted and actual environments precipitates an increased risk of chronic disease. Our objective was to determine if, following a high fat, high sucrose (HFS) diet challenge in adulthood, re-matching offspring to their maternal gestational diet would improve metabolic health more so than if there was no previous exposure to that diet. Animals re-matched to a high prebiotic fiber diet (HF) had lower body weight and adiposity than animals re-matched to a high protein (HP) or control (C) diet and also had increased levels of the satiety hormones GLP-1 and PYY (p < 0.05). Control animals, whether maintained throughout the study on AIN-93M, or continued on HFS rather than reverting back to AIN-93M, did not differ from each other in body weight or adiposity. Overall, the HF diet was associated with the most beneficial metabolic phenotype (body fat, glucose control, satiety hormones). The HP diet, as per our previous work, had detrimental effects on body weight and adiposity. Findings in control rats suggest that the obesogenic potential of the powdered AIN-93 diet warrants investigation.

Milk Collection in the Rat Using Capillary Tubes and Estimation of Milk Fat Content by Creamatocrit.

Milk, as the sole source of nutrition for the newborn mammal, provides the necessary nutrients and energy for offspring growth and development. It also contains a vast number of bioactive compounds that greatly affect the development of the neonate. The analysis of milk components will help elucidate key factors that link maternal metabolism and health with offspring growth and development. The laboratory rat represents a popular model organism for maternal studies, and rat milk can be used to examine the effect of various maternal physiological, nutritional, and pharmacological interventions on milk components, which may then impact offspring health. Here a simple method of manually collecting milk from the lactating rat that can be performed by a single investigator, does not require specialized vacuum or suction equipment, and provides sufficient milk for subsequent downstream analysis is described. A method for estimating the fat content of milk by measuring the percentage of cream within the milk sample, known as the creamatocrit, is also presented. These methods can ultimately be used to increase insight into maternal-child health and to elucidate maternal factors that are involved in proper growth and development of offspring.

Postnatal prebiotic fiber intake in offspring exposed to gestational protein restriction has sex-specific effects on insulin resistance and intestinal permeability in rats.

Maternal protein restriction (PR) during pregnancy is known to have numerous adverse effects on offspring, including increased adiposity and impaired glucose tolerance later in life. A few studies have shown that this adverse programming can be reversed by dietary or hormonal therapies early in postnatal life. The objective of this study was to determine if a weaning diet high in prebiotic fiber could mitigate some of the negative effects of maternal PR, such as increased adiposity and impaired glucose tolerance. Wistar rats were fed a low- (8%) or normal- (20%) protein diet during pregnancy. Male and female pups were weaned onto control (C; 5% fiber, 20% protein) or high (prebiotic) fiber (HF; 21% wt:wt, 1:1 ratio oligofructose and inulin at 4-10 wk; 10% wt:wt, 1:1 ratio oligofructose and inulin at 10-24 wk; 17.3% protein) diets. At 24 wk of age, glucose tolerance, body composition, satiety hormones, gut microbiota, and markers of intestinal permeability were measured in the offspring. Maternal PR reduced offspring birth weight by 5% and lean mass by 9% compared with the C offspring (P < 0.007). HF-fed offspring had lower body weights and percentage body fat (∼23% in males, ∼19% in females) at 24 wk than did C offspring (P < 0.02). Compared with C pups, pups fed the HF diet had greater cecal Bifidobacterium spp. (>5-fold) and plasma concentrations of the gut trophic hormone glucagon-like peptide 2 (GLP-2) (P < 0.05). In male PR offspring fed the HF diet, insulin resistance measured by the homeostasis model assessment of insulin resistance was reduced by 81% compared with those fed the C diet (P = 0.02). In female PR offspring fed the HF diet, plasma endotoxin was greater and colonic tight junction protein 1 (Tjp1) expression was lower than in those fed the C diet. A high prebiotic fiber weaning diet mitigated increased adiposity and insulin resistance associated with maternal PR, which could improve health and decrease risk of chronic disease in offspring born to malnourished dams. However, the functional importance of sex-specific changes in markers of intestinal barrier function warrants further investigation.

Maternal high-protein or high-prebiotic-fiber diets affect maternal milk composition and gut microbiota in rat dams and their offspring.

OBJECTIVE: Maternal gut microbiota and milk composition could modify offspring microbiota and therefore disease susceptibility. The effect of maternal high-protein (HP) or prebiotic diets on maternal milk composition and gut microbiota in rat dams and offspring was examined. METHODS: Wistar rat dams were fed a control, HP (40% wt/wt), or high-prebiotic-fiber (21.6% wt/wt) (HF) diet throughout pregnancy and lactation. Pups were challenged with a high-fat/sucrose diet from 14.5 to 22.5 weeks of age. Dam milk was analyzed for fat, protein, and oligosaccharides (OS). Fecal microbiota was analyzed in dams at parturition and 2 weeks post-partum and in offspring at 5 and 22 weeks along with cecal digesta at termination. RESULTS: Maternal milk differed only in OS content, each diet group being distinguishable. HF1 and HP1 offspring had decreased plasma lipopolysaccharide compared with C1. Offspring sex, maternal diet, and time (5 weeks vs. 22 weeks of age) affected the microbial groups examined. Bifidobacteria was higher in HF dams and offspring. CONCLUSIONS: Increasing protein or fiber content in maternal diet during pregnancy and lactation modifies milk OS content and gut microbiota of dams which may influence establishment of gut microbiota in offspring.

A maternal high-protein diet predisposes female offspring to increased fat mass in adulthood whereas a prebiotic fibre diet decreases fat mass in rats.

The negative effects of malnourishment in utero have been widely explored; the effects of increased maternal macronutrient intake are not known in relation to high fibre, and have been inconclusive with regard to high protein. In the present study, virgin Wistar dams were fed either a control (C), high-protein (40 %, w/w; HP) or high-prebiotic fibre (21·6 %, w/w; HF) diet throughout pregnancy and lactation. Pups consumed the C diet from 3 to 14·5 weeks of age, and then switched to a high-fat/sucrose diet for 8 weeks. A dual-energy X-ray absorptiometry scan and an oral glucose tolerance test were performed and plasma satiety hormones measured. The final body weight and the percentage of body fat were significantly affected by the interaction between maternal diet and offspring sex: weight and fat mass were higher in the female offspring of the HP v. HF dams. No differences in body weight or fat mass were seen in the male offspring. There was a significant sex effect for fasting and total AUC for ghrelin and fasting GIP, with females having higher levels than males. Liver TAG content and plasma NEFA were lower in the offspring of high-prebiotic fibre dams (HF1) than in those of high-protein dams (HP1) and control dams (C1). Intestinal expression of GLUT2 was decreased in HF1 and HP1 v. C1. The maternal HP and HF diets had lasting effects on body fat and hepatic TAG accumulation in the offspring, particularly in females. Whereas the HP diet predisposes to an obese phenotype, the maternal HF diet appears to reduce the susceptibility to obesity following a high-energy diet challenge in adulthood.

Satiety hormone and metabolomic response to an intermittent high energy diet differs in rats consuming long-term diets high in protein or prebiotic fiber.

Large differences in the composition of diet between early development and adulthood can have detrimental effects on obesity risk. We examined the effects of an intermittent high fat/sucrose diet (HFS) on satiety hormone and serum metabolite response in disparate diets. Wistar rat pups were fed control (C), high prebiotic fiber (HF) or high protein (HP) diets (weaning to 16 weeks), HFS diet challenged (6 weeks), and finally reverted to their respective C, HF, or HP diet (4 weeks). At conclusion, measurement of body composition and satiety hormones was accompanied by (1)H NMR metabolic profiles in fasted and postprandial states. Metabolomic profiling predicted dietary source with >90% accuracy. The HF group was characterized by lowest body weight and body fat (P<0.05) and increased satiety hormone levels (glucagon-like peptide 1 and peptide-YY). Regularized modeling confirmed that the HF diet is associated with higher gut hormone secretion that could reflect the known effects of prebiotics on gut microbiota and their fementative end products, the short chain fatty acids. Rats reared on a HF diet appear to experience fewer adverse effects from an intermittent high fat diet in adulthood when rematched to their postnatal diet. Metabolite profiles associated with the diets provide a distinct biochemical signature of their effects.

Consumption of diets high in prebiotic fiber or protein during growth influences the response to a high fat and sucrose diet in adulthood in rats.

BACKGROUND: Early dietary exposure can influence susceptibility to obesity and type 2 diabetes later in life. We examined the lasting effects of a high protein or high prebiotic fiber weaning diet when followed by a high energy diet in adulthood. METHODS: At birth, litters of Wistar rats were culled to 10 pups. At 21 d pups were weaned onto control (C), high prebiotic fiber (HF) or high protein (HP) diet. Rats consumed the experimental diets until 14 wk when they were switched to a high fat/sucrose (HFHS) diet for 6 wk. Body composition and energy intake were measured and an oral glucose tolerance test (OGTT) performed. Blood was analyzed for satiety hormones and tissues collected for real-time PCR. RESULTS: Weight gain was attenuated in male rats fed HF from 12 wk until study completion. In females there were early reductions in body weight that moderated until the final two wk of HFHS diet wherein HF females weighed less than HP. Final body weight was significantly higher following the high fat challenge in male and female rats that consumed HP diet from weaning compared to HF. Lean mass was higher and fat mass lower with HF compared to HP and compared to C in males. Energy intake was highest in HP rats, particularly at the start of HFHS feeding. Plasma glucose was higher in HP rats compared to HF during an OGTT. Plasma amylin was higher in HF females compared to C and glucagon-like peptide-1 (GLP-1) was higher in HF rats during the OGTT. Leptin was higher in HP rats during the OGTT. HF upregulated GLUT 5 mRNA expression in the intestine and downregulated hepatic hydroxymethylglutaryl coenzyme A reductase. Male rats fed HP had higher hepatic triglyceride content than C or HF. CONCLUSION: These data suggest that while a long-term diet high in protein predisposes to an obese phenotype when rats are given a high energy diet in adulthood, consumption of a high fiber diet during growth may provide some protection.