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: 10573241
• 负责人: MULCHAND S PATEL
• 金额: $ 21.03万
• 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 2025-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10573241
• 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; Gynecologic; Health; Health Promotion; Healthcare; Hematology; Hormones; Human; Human Milk; Hyperphagia; Hypothalamic structure; Infertility; Inflammation Mediators; Institute of Medicine (U.S.); Insulin; 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; 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; 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.

美国 50% 的孕妇超重或肥胖，这不仅使母亲的健康面临风险，而且还给后代在出生之前就带来了沉重的医疗负担。母亲孕前肥胖与妊娠期体重过度增加（GWG）以及子宫内和产后环境中的代谢不良有关，使后代暴露于过度的发育信号（例如激素、葡萄糖、脂质和炎症介质）下，从而对成年期的疾病风险结果产生负面影响。医学研究所建议超重/肥胖的准妈妈接受饮食和运动咨询以限制体重增长，然而，大多数肥胖女性由于各种实际（缺乏时间、动力）和生理（食欲变化、疲劳）原因，对怀孕期间的生活方式干预表现出适度且可变的反应。尽管女性可能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缺乏改善。此外，尽管怀孕前时期被认为是生活方式的改变可以预防有害的儿童结局的关键窗口期，但高意外怀孕率（美国为 51%）并不能提供这个机会。鉴于目前改善产妇孕前BMI和限制GWG的生活方式干预措施存在广泛局限性，严重缺乏有效解决日益严重的产妇肥胖问题的治疗方案。一种有前途但本质上尚未探索的选择可能是在天然保健品的膳食补充剂中找到已确定的抗肥胖和代谢健康促进反应。 α-硫辛酸 (αLPA) 在营养保健品中引人注目，因为它具有广泛的代谢益处，据称具有抗肥胖、抑制食欲、降低血糖和胰岛素增敏作用。然而，尚未在孕产妇肥胖的背景下对其作为预防性疗法进行检验，以防止不良的规划结果。因此，我们的提案有两个具体目标： i) 描述肥胖妊娠期间母体和胎儿对膳食 αLPA 补充剂的代谢适应情况； ii) 确定母体 αLPA 补充剂对预防后代整个生命过程中围产期肥胖和相关代谢功能障碍的影响。我们将使用一种经过充分表征的饮食诱导肥胖妊娠大鼠模型来破坏胎儿胰腺β细胞功能和下丘脑食欲调节神经肽信号传导，从而导致成年肥胖和葡萄糖耐受不良。我们将探讨在整个孕前、妊娠期和哺乳期补充 αLPA 的安全性和有效性，作为防止肥胖妊娠后代出现适应不良编程反应的一种手段。该提案中的想法应被认为是高度探索性的，如果成功，将对早期肥胖预防策略产生很大影响，并为推进 αLPA 的新应用提供知情的理解。