The mechanistic basis for improved metabolic health in females following lactation

改善女性哺乳后代谢健康的机制基础

• 批准号: 8872898
• 负责人: Wendy R Hood
• 金额: $ 7.4万
• 依托单位: AUBURN UNIVERSITY AT AUBURN
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-02-18 至 2017-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8872898
• 关键词: Adipocytes; Adipose tissue; Age; Amino Acids; Animal Model; Animals; Antioxidants; Biogenesis; Birth; Breast Feeding; Breeding; Cell physiology; Child; Complex; Deposition; Development; Disease; Drops; Eating; Electron Transport; Energy Metabolism; Fatty acid glycerol esters; Female; Fetus; Functional disorder; Future; Glucose; Goals; Health; Histocompatibility Testing; Hypertension; Incidence; Individual; Intervention; Lactation; Lipid Peroxidation; Lipids; Liver; Malignant neoplasm of ovary; Mammary gland; Manganese Superoxide Dismutase; Measures; Mediating; Metabolic; Metabolic Diseases; Metabolism; Milk; Mitochondria; Mitochondrial Proteins; Monitor; Mothers; Muscle; Non-Insulin-Dependent Diabetes Mellitus; Nuclear Receptors; Nurses; Obesity; Organ; PPAR gamma; Pattern; Peroxisome Proliferator-Activated Receptors; Physiological; Play; Pregnancy; Probability; Process; Production; Proteins; Randomized; Rattus; Reactive Oxygen Species; Regulation; Relative (related person); Reproduction; Respiration; Risk; Role; Skeletal Muscle; Spectrum Analysis; System; Techniques; Tissues; Transcription Coactivator; Uterine Cancer; Variant; Visceral; Weaning; Western Blotting; Woman; Women' s Health Nursing; Work; aged; base; cancer type; catalase; child bearing; copper zinc superoxide dismutase; density; differential expression; experience; fasting glucose; glutathione peroxidase; improved; insight; insulin sensitivity; lipid metabolism; malignant breast neoplasm; metabolic rate; obesity risk; offspring; oxidation; oxidative damage; public health relevance; research study; respiratory; screening; therapy development; uptake

 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.

 描述(申请人提供)：母乳喂养不仅改善哺乳婴儿的健康和发育，而且对母亲的健康也有持久的好处，包括减少肥胖症和II型糖尿病的发生率。断奶后，乳酸盐雌性的内脏脂肪细胞较少，空腹血糖较低，胰岛素敏感度较高，与生育但不哺乳的雌性和根本不繁殖的雌性相比，循环中的血脂减少。根据哺乳重置假说，已提出哺乳期在重置女性代谢性疾病风险方面起着核心作用，但导致这种影响的机制在很大程度上仍未被探索。该项目的目的是评估哺乳到断奶的雌性大鼠(PL)、已经生育但没有哺乳的年龄匹配的雌性大鼠(P)和年龄匹配的未生育的雌性大鼠(NR)之间整个动物和细胞代谢差异的机制。这项研究将以大鼠作为我们的模型生物。比较各处理组大鼠断奶后及3个月后全动物代谢率及肝脏、骨骼肌和白色脂肪组织线粒体的变化。这些值将根据繁殖前、妊娠后期和哺乳峰值进行评估，以确定代谢模式是否指示通过哺乳重新建立到繁殖前的值。根据它们在调节脂质氧化和线粒体生物发生中的作用，将评估每组中过氧化物酶体增殖物激活受体和PCG转录辅助激活物的相对表达，以确定它们在哺乳期后刺激长期生理代谢变化的潜力。此外，氧化损伤的变化也将在不同组之间进行比较，作为线粒体维持器官健康能力的指标。这项工作的结果将提高我们对哺乳期如何改善整个动物新陈代谢和细胞生理学的理解，并为未来的研究提供目标，评估针对无法长期哺育孩子的妇女和不能生育的妇女的干预措施。