Prevention of obesity in Infants of overweight and obese women

预防超重和肥胖女性婴儿的肥胖

• 批准号: 10409647
• 负责人: Mina Desai
• 金额: $ 19.26万
• 依托单位: LUNDQUIST INSTITUTE FOR BIOMEDICAL INNOVATION AT HARBOR-UCLA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-06-01 至 2024-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10409647
• 关键词: Address; Adult; Age-Months; Animals; Birth; Body mass index; Brain; Breast Feeding; Calories; Childhood; Clinical Trials; Cognitive; Desire for food; Development; Dietary intake; Eating; Economic Burden; Energy Intake; Environment; Epidemic; Epigenetic Process; Exhibits; Exposure to; Fatty acid glycerol esters; Food Intake Regulation; Fostering; Gender; Generations; Gestational Age; Growth; High Fat Diet; Human Milk; Hyperphagia; Hypothalamic structure; Incidence; Infant; Infant Development; Infant Food; Infant formula; Intake; Interruption; Intervention; Laboratory Study; Leptin resistance; Life; Litter Size; Metabolic syndrome; Milk; Nerve Degeneration; Neurodevelopmental Disorder; Neurons; Newborn Infant; Non obese; Nutritional; Obesity; Overweight; Perinatal; Prevention strategy; Public Health; Rattus; Risk; Satiation; Signal Transduction; Structure of nucleus infundibularis hypothalami; Weight; Weight Gain; Woman; adult obesity; clinical application; early-onset obesity; excessive weight gain; fetal; in utero; increased appetite; infant adiposity; innovation; maternal obesity; milk intake; newborn adiposity; novel; obese mothers; obesity in children; obesity prevention; offspring; prevent; programs; rapid weight gain; relating to nervous system

Throughout the world, obesity and metabolic syndrome are an ongoing epidemic crisis, presenting major public health challenges and significant economic burdens. The developmental programming effects of the in-utero environment is demonstrated by the increased risk of large for gestational age (LGA) newborns and childhood and adult obesity in offspring of overweight/obese (OW/OB) mothers. Animal studies have confirmed that maternal obesity and high fat diet programs the offspring appetite center, the arcuate nucleus, resulting in offspring hyperphagia and rapid weight gain, contributing to the generational cycle of obesity. Compounding the effect of programmed hyperphagia is the impact of breast milk caloric content. Despite evidence that breastfeeding reduces the incidence of childhood obesity, breastfeed LGA infants’ childhood obesity rates are nearly 50% greater than formula fed appropriate for gestational age infants. Maternal BMI and dietary intake are highly correlated with milk total calorie and fat content. Our laboratory studies show that offspring born to and nursed by obese rat dams exhibit hyperphagia and develop early life and adult obesity. In contrast, if these offspring are cross fostered and nursed by non-obese dams (matched for gender and litter-size), the offspring grow to normal weight and BMI as adults. These studies suggest that despite programmed offspring hyperphagia at birth, the restriction to control dam milk prevents excessive newborn weight gain and obesity. We propose that normalized caloric intake and newborn growth will prevent the onset of infant obesity, hyperleptinemia (and leptin resistance), and thus normalize appetite throughout childhood. The proposed studies will 1) Confirm that OW/OB mothers’ milk has increased total calorie content and that infants of OW/OB mothers have increased milk intake, and as an intervention 2) Determine if titrated human milk or formula calorie intake prevents excessive infant weight gain in the first six months of life. This highly innovative study will examine the potential efficacy of a novel preventative strategy to prevent the development of infant obesity and interrupt the generational cycle of obesity.

在全世界，肥胖和代谢综合征是一种持续的流行病危机，带来了重大的公共卫生挑战和重大的经济负担。宫内环境的发育编程效应通过超重/肥胖（OW/OB）母亲的后代中大于胎龄（LGA）新生儿以及儿童和成人肥胖的风险增加来证明。动物研究证实，母体肥胖和高脂饮食程序影响了后代的食欲中枢--弓状核，导致后代食欲过盛和体重迅速增加，促成了肥胖的世代循环。母乳热量含量的影响加剧了程序性食欲过盛的影响。尽管有证据表明母乳喂养可以降低儿童肥胖的发生率，但母乳喂养的LGA婴儿的儿童肥胖率比适合胎龄婴儿的配方奶粉高出近50%。母亲BMI和膳食摄入量与牛奶总热量和脂肪含量高度相关。我们的实验室研究表明，出生和喂养的肥胖大鼠母鼠的后代表现出暴食症和发展早期生活和成年肥胖。相比之下，如果这些后代由非肥胖的母鼠（性别和窝仔数匹配）交叉培养和喂养，后代长大后体重和BMI正常。这些研究表明，尽管出生时有程序性的后代摄食过多，但控制母奶的限制可以防止新生儿体重过度增加和肥胖。我们认为，正常的热量摄入和新生儿的生长将防止婴儿肥胖，高瘦素血症（和瘦素抵抗）的发生，从而使整个儿童期的食欲正常化。拟议的研究将：1）证实OW/OB母亲的乳汁总热量含量增加，OW/OB母亲的婴儿的乳汁摄入量增加，并作为干预措施2）确定滴定的母乳或配方奶热量摄入是否可防止婴儿在出生后前六个月体重过度增加。这项高度创新的研究将研究一种新的预防策略的潜在功效，以防止婴儿肥胖的发展，并中断肥胖的世代周期。

项目成果

TNFα-Induced Oxidative Stress and Mitochondrial Dysfunction Alter Hypothalamic Neurogenesis and Promote Appetite Versus Satiety Neuropeptide Expression in Mice.

• DOI: 10.3390/brainsci12070900
• 发表时间: 2022-07-09
• 期刊: BRAIN SCIENCES
• 影响因子: 3.3
• 作者: Desai, Mina;Stiles, Linsey;Torsoni, Adriana S.;Torsoni, Marcio A.;Shirihai, Orian S.;Ross, Michael G.
• 通讯作者: Ross, Michael G.