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.

Maternal consumption of high-prebiotic fibre or -protein diets during pregnancy and lactation differentially influences satiety hormones and expression of genes involved in glucose and lipid metabolism in offspring in rats.

Risk of developing the metabolic syndrome may be influenced by nutritional environment early in life. We examined the effects of high-fibre (HF) and high-protein (HP) diets consumed during pregnancy and lactation on satiety hormones and expression of genes involved in glucose and lipid metabolism in offspring. Wistar dams were fed a control (C), HF or HP diets during pregnancy and lactation. At parturition, litters were culled to ten pups. At 21 d, all pups were weaned onto C diet. At 7, 14, 21, 28 and 35 d after birth, blood was analysed for satiety hormones and tissues for mRNA expression in offspring. No differences were observed in litter size or birth weight. At 21 d, offspring of HF dams had greater adjusted intestinal mass and lower liver weight than those of C but not of HP dams. Plasma glucose at 28 d and amylin at 7, 14 and 28 d were lower in HF v. C and HP offspring. Glucagon-like peptide-1 was higher in HP offspring than in HF offspring at 7 d but was higher in HF v. C offspring at 21 d. Offspring of HF dams had higher glucose transporter (GLUT2 and Na+-dependent glucose/galactose transporter) mRNA expression at 21 d v. C and HP offspring. In brown adipose tissue, HF and HP up-regulated uncoupling protein-1 and PPAR-γ coactivator. HP was associated with increased resistin and IL-6 mRNA expression. The present study demonstrates that maternal diet composition differentially regulates circulating satiety hormones and genes involved in glucose transport and energy metabolism in offspring. These early changes could have long-term consequences for obesity risk.

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.

Long-term dietary restriction influences plasma ghrelin and GOAT mRNA level in rats.

The objective of this study was to examine the effect of chronic dietary restriction on the physical characteristics of the intestine and gut-derived satiety hormone production. Male Wistar rats (8 weeks) were randomized to ad libitum (AL) or 35% dietary restriction (DR) for 5 months. At the end of the study, physical measurements were made on the intestine and satiety hormone secretion and mRNA expression determined. A comparison group of young, growing AL rats (5 weeks) was also examined. The adult DR rats gained less weight over 5 months and had lower fat mass than adult AL rats (p<0.05). The weight of the small intestine as a percentage of total body weight was greater in adult DR compared to adult AL but lower than young AL rats. Compared to AL, DR down-regulated proglucagon and cholecystokinin mRNA in the duodenum and ghrelin mRNA in the stomach of adult rats but was not different from young AL. Ghrelin-O-acyltransferase (GOAT) mRNA in the stomach was up-regulated 21-fold in adult AL rats compared to young AL and 14-fold compared to adult DR rats. Total and des-acyl ghrelin was approximately 50% higher in adult DR and young AL rats compared to adult AL. Plasma leptin and insulin were lower in adult DR and young AL rats compared to adult AL. Our findings suggest that long-term energy deficits continue to drive up ghrelin levels which may have profound implications for practical implementation of DR as an anti-aging or anti-obesity strategy in humans.

Changes in satiety hormones and expression of genes involved in glucose and lipid metabolism in rats weaned onto diets high in fibre or protein reflect susceptibility to increased fat mass in adulthood.

Risk of developing obesity and diabetes may be influenced by the nutritional environment early in life. We examined the effects of high fibre or protein diets on satiety hormones and genes involved in glucose and lipid metabolism during postnatal development and on adult fat mass. At 21 days of age, Wistar rat pups were weaned onto control (C), high fibre (HF) or high protein (HP) diet. Tissue and blood were collected at 7, 14, 21, 28 and 35 days after birth. A second group of rats consumed the weaning diets until 4 months when they were switched to a high fat-high sugar diet for 6 weeks, after which body and fat mass and plasma glucose were determined. In young rats, HF diet increased plasma glucagon-like peptide (GLP-1) compared to C and HP and decreased leptin compared to C at postnatal days 28 and 35. Hepatic fatty acid synthase mRNA was down-regulated by HF and HP compared to C at days 28 and 35. In brown adipose tissue, HF increased uncoupling protein-3 mRNA whereas HP increased mRNA of the inflammatory cytokine interleukin-6. Body weight, fat mass and glycaemia in adult males and fat mass in females were greater after the high fat challenge in rats that consumed the HP diet from weaning. Increasing fibre or protein in postnatal diets causes rapid change in satiety hormone secretion and genes involved in glucose and lipid metabolism which appear to influence fat mass and glycaemia in adulthood, high protein being associated with increased susceptibility to obesity.