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|Title:||Influence of Nutrients on Developmental Programming of Glucose and Lipid Metabolism in a Wistar Rat Model|
|Author:||Hallam, Megan Carroll|
|Abstract:||Objectives: To determine the effects of pre-natal diets high in protein or prebiotic fiber on offspring health in adulthood and to examine the potential for postnatal prebiotic fiber to mitigate the metabolic malprogramming associated with maternal protein restriction during pregnancy. Methods: Three main studies were performed. Maternal diets high in prebiotic fiber (21.6%; HF) or protein (40%, HP) were compared with control. Gut microbiota and milk were analyzed in the dams along with adult offspring body composition, plasma satiety hormones and gut microbiota after a high fat/sucrose (HFS) dietary challenge. Re-matching to maternal diet after the HFS challenge was examined in the second study. The HF diet was further examined as a weaning diet in offspring malprogrammed due to gestational protein restriction (PR) in the third study. Results: Two oligosaccharides were increased in maternal milk of HP and HF dams. HF dams also had increased levels of bifidobacteria compared to HP and C. In the offspring, HF diets decreased body weight and adiposity, and increased plasma PYY and the abundance of bifidobacteria in the gut across all studies. The HP diet increased offspring body weight and adiposity, but decreased HOMA-IR scores. Liver triglycerides were also increased, which in the second study was accompanied by upregulation of hepatic lipogenic genes (SREBP1c, ACC, FAS). In the first two studies HF decreased plasma lipopolysaccharide, a measure of metabolic endotoxemia. Re-matching to maternal diet blunted the typical response to the HF and HP diets with increased fasting glucose, energy intake and decreased bone mineral density seen in re-matched versus naïve offspring. In the final study with malprogrammed offspring, HF improved HOMA-IR scores in male offspring but also increased markers of intestinal permeability in female PR offspring. Conclusions: A maternal diet high in prebiotic fiber prevented excessive weight and adiposity gain in adult offspring during an HFS dietary challenge. While improving HOMA-IR scores, the HP diet lead to increased adiposity and increased hepatic lipogenesis. A weaning diet high in prebiotic fiber has beneficial effects on body weight and adiposity, plasma satiety hormones, glycemia and gut microbiota in malprogrammed offspring.|
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