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

• 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
• 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

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，50%的孕妇超重或肥胖，这不仅危及母亲的健康，而且在后代出生前就给他们带来了巨大的医疗负担。母亲孕前肥胖与妊娠体重过度增加(GWG)和子宫和出生后环境中的代谢不良有关，这些环境会使后代暴露于夸大的发育信号(如激素、葡萄糖、血脂和炎症介质)，这些信号对成年后的疾病风险结果产生负面影响。医学研究所建议超重/肥胖的孕妇接受饮食和运动咨询，以限制GWG，然而，由于各种实际(缺乏时间、动力)和生理(食欲改变、疲劳)的原因，大多数肥胖妇女在怀孕期间对生活方式干预表现出温和和多变的反应。尽管女性可能会有动力改善饮食模式，但据报道，怀孕前和怀孕期间的饮食质量都没有改善。此外，尽管孕前被认为是改变生活方式可以防止有害儿童结局的关键窗口，但计划外怀孕的高比率(在美国为51%)并没有提供这一机会。鉴于目前在改善孕妇孕前体重指数和限制GWG方面的生活方式干预措施的广泛局限性，严重缺乏有效解决日益严重的产妇肥胖问题的治疗选择。在天然保健品的饮食补充中可能会发现一个有希望的、但基本上未被探索的选择，该产品具有既定的抗肥胖和代谢健康促进反应。α-硫辛酸(αLPA)在营养食品中是值得注意的，因为它具有广泛的代谢益处，据称具有抗肥胖、抑制食欲、降血糖和胰岛素增敏的作用。然而，尚未在母亲肥胖的背景下对其进行审查，将其作为预防方案编制结果的预防性疗法。因此，我们的建议有两个特别的目的：i)表征肥胖妊娠孕妇和胎儿对膳食α低密度脂蛋白补充的代谢适应；以及ii)确定母亲补充α低密度脂蛋白在预防围产期肥胖和子代整个生命过程中相关代谢障碍方面的影响。我们将使用一个具有良好特征的饮食诱导肥胖妊娠大鼠模型来编程胎儿胰岛β细胞功能和下丘脑食欲调节神经肽信号，从而导致成人发作性肥胖和糖耐量异常。母体αLPA在孕前、孕期和哺乳期补充的安全性和有效性将被作为一种手段来预防肥胖怀孕的后代的不良适应编程反应。这项建议中的想法应该被认为是高度探索性的，如果成功，将对早期肥胖预防策略产生高度影响，并为推进αLPA的新应用提供知情的理解。