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.

Public Health Relevance

Breastfeeding has many benefits for both the development and health of the offspring and for the health of the mother. Why the health of women that nurse their young is improved over women that reproduce but not breastfeed and women that never reproduce at all remains largely unexplored. Results from these experiments will be used to take a targeted approach in evaluating interventions for women that are unable to nurse their young for an extended period and women who do not or cannot reproduce.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Small Research Grants (R03)
Project #
5R03HD083654-02
Application #
9015446
Study Section
Biobehavioral and Behavioral Sciences Subcommittee (CHHD)
Program Officer
Raiten, Daniel J
Project Start
2015-02-18
Project End
2018-01-31
Budget Start
2016-02-01
Budget End
2018-01-31
Support Year
2
Fiscal Year
2016
Total Cost
Indirect Cost
Name
Auburn University at Auburn
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
066470972
City
Auburn University
State
AL
Country
United States
Zip Code
36849
Hyatt, Hayden W; Zhang, Yufeng; Hood, Wendy R et al. (2018) Physiological, mitochondrial, and oxidative stress differences in the presence or absence of lactation in rats. Reprod Biol Endocrinol 16:2
Zhang, Yufeng; Brasher, Adam L; Park, Noel R et al. (2018) High activity before breeding improves reproductive performance by enhancing mitochondrial function and biogenesis. J Exp Biol 221:
Zhang, Yufeng; Humes, Frances; Almond, Gregory et al. (2018) A mitohormetic response to pro-oxidant exposure in the house mouse. Am J Physiol Regul Integr Comp Physiol 314:R122-R134
Hood, W R; Zhang, Y; Mowry, A V et al. (2018) Life History Trade-offs within the Context of Mitochondrial Hormesis. Integr Comp Biol 58:567-577
Zhang, Yufeng; Kallenberg, Christine; Hyatt, Hayden W et al. (2017) Change in the Lipid Transport Capacity of the Liver and Blood during Reproduction in Rats. Front Physiol 8:517
Hyatt, Hayden W; Zhang, Yufeng; Hood, Wendy R et al. (2017) Lactation has persistent effects on a mother's metabolism and mitochondrial function. Sci Rep 7:17118
Zhang, Yufeng; Hood, Wendy R (2016) Current versus future reproduction and longevity: a re-evaluation of predictions and mechanisms. J Exp Biol 219:3177-3189