Alpha Lipoic Acid as a Maternal Supplement in Obese Pregnancies

α-硫辛酸作为肥胖孕妇的母体补充剂

基本信息

批准号：
10373662
负责人：
MULCHAND S PATEL
金额：
$ 23.93万
依托单位：
STATE UNIVERSITY OF NEW YORK AT BUFFALO
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-02-15 至 2024-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10373662
关键词：
Address Adult Adult Children Animals Attention Biological Biological Factors Body Weight decreased Body mass index Calories Cell physiology Cells Chemistry Child Chronic Disease Counseling Data Desire for food Development Diet Dietary Supplementation Discipline of obstetrics Disease Outcome Eating Environment Exercise Exposure to Fatigue Fatty acid glycerol esters Female of child bearing age Fetal Development Fetal health Functional disorder Future Generations Glucose Glucose Intolerance Goals Health Health Promotion Healthcare Hematology Hormones Human Human Milk Hyperphagia Hypothalamic structure Infertility Inflammation Mediators Institute of Medicine (U.S.)Intervention Lactation Life Cycle Stages Life Style Maternal Health Metabolic Metabolic Diseases Metabolic dysfunction Metabolism Micronutrients Modeling Mothers Motivation Neuropeptides Nutraceutical Nutritional Obesity Outcome Overweight Pancreas Pathologic Pattern Performance Perinatal Physiological Plants Positioning Attribute Predisposition Pregnancy Pregnancy Complications Pregnancy Outcome Pregnant Women Premature Birth Prevalence Prevention Prevention strategy Preventive therapy Property Rattus Recommendation Reporting Research Risk Safety Serum Signal Transduction Spontaneous abortion Sprague-Dawley Rats Structure of beta Cell of islet Supplementation Testing Thioctic Acid Time United States Weaning Woman Work base cardiometabolism care burden diet and exercise diet-induced obesity dietary dietary supplements disorder risk effective intervention endometriosis experience fetal gestational weight gain health of the mother improved in utero insight insulin sensitivity insulin sensitizing drugs lifestyle intervention lipid mediator maternal obesity maternal safety mother nutrition novel obese mothers obesity in pregnancy obesity prevention obesity treatment offspring postnatal prepregnancy prepregnancy obesity prevent programs pup reproductive response unintended pregnancy

项目摘要

Fifty-percent of pregnant women in the US are overweight or obese, putting not only the mother’s health at risk but also placing a substantial health care burden on future generations before they are even born. Maternal pre-pregnancy obesity is associated with excessive gestational weight gain (GWG) and metabolic adverse in utero and postnatal environments that expose offspring to exaggerated developmental signals (e.g. hormones, glucose, lipids, and inflammatory mediators) that negatively impact disease risk outcomes in adulthood. The Institute of Medicine recommends that overweight/obese expectant mothers receive dietary and exercise counselling to limit GWG, however, most obese women demonstrate modest and variable responses to lifestyle interventions during pregnancy for various practical (lack of time, motivation) and physiological (change in appetite, fatigue) reasons. Although women may be motivated to improve eating patterns, a lack of improvement in dietary quality both before and during pregnancy has been reported. Further, although the pre-pregnancy period is regarded as a critical window where lifestyle changes could prevent harmful child outcomes, the high rate of unplanned pregnancies (51% in the US) do not provide this opportunity. Given the breadth of current limitations in lifestyle interventions to improve maternal pre-pregnancy BMI and limit GWG, there is a serious lack of treatment options that effectively address the ever-growing problem of maternal obesity. A promising, yet essentially unexplored, option may be found in dietary supplementation of natural health products with established anti-obesity and metabolic health-promoting responses. α-lipoic acid (αLPA) is notable amongst nutraceuticals as it offers a wide array of metabolic benefits with purported anti-obesity, appetite-suppressing, glucose lowering, and insulin sensitizing effects. However, it has yet to be examined in the context of maternal obesity as a preventative therapy to protect against adverse programming outcomes. Therefore, our proposal has two Specific Aims: i) To characterize maternal and fetal metabolic adaptations to dietary αLPA supplementation in obese pregnancies; and ii) To determine the influence of maternal αLPA supplementation in protecting against perinatal programming of obesity and associated metabolic dysfunction in offspring throughout the life course. We will use a well-characterized diet-induced obese pregnancy rat model to malprogram fetal pancreatic beta cell function and hypothalamic appetite-regulating neuropeptide signaling resulting in adult-onset obesity and glucose intolerance. The safety and efficacy of maternal αLPA supplementation throughout pre- pregnancy, gestation, and lactation will be explored as a means to protect against maladaptive programming responses in offspring from obese pregnancies. The ideas in this proposal should be considered highly exploratory that, if successful, would have a high degree of impact for early obesity prevention strategies and provide an informed understanding to advance novel applications for αLPA.

在美国，有51％的孕妇超重或肥胖，不仅使母亲的健康受到威胁，而且还会在其出生之前对子孙后代进行二级医疗保健。孕妇孕前肥胖与子宫和产后环境中的胎儿体重增加（GWG）和代谢广告有关，这些环境暴露于夸张的发育信号（例如激素，葡萄糖，脂质，脂质和炎症介体），从而对疾病的风险产生负面影响。医学研究所建议，超重/肥胖的母亲会接受饮食和运动咨询以限制GWG，但是，大多数肥胖女性在怀孕期间对各种实用（缺乏时间，动机）和生理学（食欲，疲劳，疲劳的变化）的怀孕期间对生活方式干预的反应适中和可变反应。尽管妇女可能会被激励改善饮食方式，但据报道，怀孕之前和怀孕期间缺乏饮食质量的改善。尽管怀孕前时期被认为是生活方式改变可以防止有害儿童结果的关键窗口，但计划外怀孕的高率（在美国为51％）并不能提供这个机会。鉴于生活方式干预措施的当前局限性以改善孕产妇的怀孕前BMI并限制GWG，因此严重缺乏治疗选择，可以有效解决孕产妇肥胖的不断增长的问题。在饮食中补充抗肥胖和代谢健康反应的天然健康产品中，可以找到一个希望，但本质上是出乎意料的选择。 α-脂肪酸（αLPA）在营养液中是值得注意的，因为它具有多种代谢益处，并具有抗肥胖，抑制作用，葡萄糖降低和胰岛素敏感性的作用。但是，在孕产妇肥胖症的背景下，它尚待进行研究，以防止不良编程的预后。因此，我们的提议具有两个具体的目的：i）表征肥胖妊娠中饮食中补充饮食αLPA的遗中和胎儿代谢的适应性； ii）确定补充母体αLPA对防止肥胖的围产期编程的影响，并在整个生命过程中后代对后代中的代谢功能障碍的影响。我们将使用特征良好的饮食诱导的肥胖大鼠模型来对胎儿胰腺β细胞功能和下丘脑食欲调节神经肽信号传导，从而导致成人肥胖和葡萄糖intlerance。将探讨在孕前，妊娠和泌乳期间补充母体αLPA的安全性和效率，以防止肥胖怀孕的后代中的适应不良的编程反应。该提案中的想法应被认为是高度探索性的，如果成功，将对早期肥胖策略产生很大的影响，并提供明智的理解，以推动对αLPA的新颖应用。