The mechanistic basis for improved metabolic health in females following lactation

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 DESCRIPTION (provided by applicant): Breastfeeding not only improves the health and development of the suckling young but it also confers lasting benefits to the health of mother including reduced incidence of obesity and type II diabetes. Following weaning, females that lactate display fewer visceral adipocytes, lower fasting glucose, increased insulin sensitivity, an reduced circulating lipids relative to females that give birth but not suckle their young and females that do not reproduce at all. By the lactation reset hypothesis, it has been proposed that lactation plays a central role in resetting a female's risk of metabolic disease yet the mechanisms responsible for this effect remain largely unexplored. The goal of the proposed project is to evaluate the mechanisms responsible for differences in whole animal and cellular metabolism between female rats that that have suckled their young to weaning (PL), age-matched female rats that have given birth but not suckled their young (P), and aged-matched female rats that have not reproduced (NR). Rats will be used as our model organism for this study. Whole-animal metabolic rate and mitochondrial profiles of liver, skeletal muscle and white adipose tissue will be compared between all treatment groups after the PL rats are weaned and again 3 months later. These values will be evaluated relative to pre-breeding, late pregnancy, and peak lactation values to determine if patterns of metabolism are indicative of the re-establishment to pre-breeding values by lactation. Based on their roles in adjusting lipid oxidation and mitochondrial biogenesis, the relative expression of peroxisome proliferator- activated receptors and PCG transcriptional coactivator will be evaluated in each group for their potential to stimulate long term physiological changes in metabolism following lactation. In addition, variation in oxidative damage will also be compared between groups as indicators of mitochondrial ability to maintain organ health. The results of this work will improve our understanding of how whole animal metabolism and cellular physiology are improved by lactation and provide targets for future studies evaluating interventions for women that are unable to nurse their young for an extended period and women who don't reproduce.