Role of perinatal diet in developmental programming of skeletal strength

围产期饮食在骨骼强度发育规划中的作用

• 批准号: 7914827
• 负责人: Maureen Devlin Hamalainen
• 金额: $ 5.05万
• 依托单位: BETH ISRAEL DEACONESS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-30 至 2013-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7914827
• 关键词: Adolescent; Adrenergic Agents; Adrenergic Receptor; Adult; Affect; Atherosclerosis; Bone Density; Bone Growth; Caloric Restriction; Carbohydrates; Data; Development; Diet; Environment; Fatty acid glycerol esters; Growth; Health; Hormonal; Human; Immune; Knock-out; Lactation; Leptin; Life; Macronutrients Nutrition; Metabolic Diseases; Mus; Neurosecretory Systems; Non-Insulin-Dependent Diabetes Mellitus; Obesity; Osteoblasts; Osteoporosis; Perinatal; Peripheral; Pregnancy; Risk Factors; Rodent; Role; Signal Transduction; Skeletal Development; Skeleton; Societies; Source; Testing; adrenergic; bone; bone mass; nutrition; postnatal; prenatal; programs; public health relevance; reproductive; research study; response; skeletal

DESCRIPTION (provided by applicant): This project tests the effects of maternal perinatal diet on skeletal acquisition. Perinatal developmental programming, triggered by perinatal caloric restriction or high fat diet, is a known risk factor for adult neuroendocrine, immune, reproductive, and metabolic disease, including obesity, atherosclerosis, and type II diabetes. However, little is known about how early life nutrition impacts skeletal development. The general hypothesis is that perinatal caloric restriction (CR) or high fat (HF) diet will initiate developmental programming that decreases postnatal bone growth and acquisition of bone mineral density. To test whether perinatal energetic status affects bone growth, mice exposed to maternal CR or HF diet during gestation/lactation will be compared to postnatally exposed mice. Previous studies have shown negative effects of CR and HF diets on bone in adult rodents, but did not test for effects on juvenile skeletal acquisition. Our specific aims include determining whether caloric availability (ad lib vs. restricted) and macronutrient source (high fat vs. high carbohydrate) during skeletal growth and/or maternal diet during pregnancy and lactation affect bone mass, microarchitecture and strength. We will also test whether prenatal diet affects the skeletal response to postnatal diet. The hypothesized mechanism for these bone-environment interactions involves signaling of energetic status by leptin, a fat-derived signal of energetic status, via ss-adrenergic receptors in bone. Thus our experiments will compare skeletal and hormonal response to prenatal and postnatal energy availability in normal mice and ss-adrenergic receptor2 knockout (ss2-AR KO) mice. By separating the effects of direct leptin action on bone from the effects of central leptin signaling in osteoblasts (absent in ss2-AR KO mice), we will generate unique data on the effects of central vs. peripheral leptin signaling on trabecular and cortical bone. PUBLIC HEALTH RELEVANCE: This project has several applications to human health. Osteoporosis and obesity are increasing markedly in society, and understanding how interactions between prenatal and postnatal nutrition affect the skeleton may help to identify mechanisms underlying attainment of bone mass and strength during growth.

描述(由申请人提供)：该项目测试母亲围产期饮食对骨骼获得的影响。由围产期热量限制或高脂肪饮食引发的围产期发育规划是成人神经内分泌、免疫、生殖和代谢疾病的已知危险因素，包括肥胖、动脉粥样硬化和II型糖尿病。然而，人们对早期生命营养如何影响骨骼发育知之甚少。一般的假设是，围产期的热量限制(CR)或高脂肪(HF)饮食将启动发育规划，从而减少出生后骨生长和骨密度的获得。为了测试围产期的能量状态是否会影响骨骼生长，在怀孕/哺乳期间接触母体CR或HF饮食的小鼠将与出生后暴露的小鼠进行比较。以前的研究表明，CR和HF饮食对成年啮齿类动物的骨骼有负面影响，但没有测试对幼年骨骼获得的影响。我们的具体目标包括确定骨骼生长和/或孕期和哺乳期母体饮食期间的卡路里供应(随机和限制)和大量营养素来源(高脂肪和高碳水化合物)是否影响骨量、微结构和强度。我们还将测试产前饮食是否会影响骨骼对出生后饮食的反应。这些骨骼-环境相互作用的假想机制涉及瘦素通过骨骼中的ss-肾上腺素能受体传递能量状态的信号，瘦素是一种脂肪来源的能量状态信号。因此，我们的实验将比较正常小鼠和SS-肾上腺素能受体2基因敲除(SS2-AR KO)小鼠对出生前和出生后能量供应的骨骼和激素反应。通过分离瘦素对骨骼的直接作用和成骨细胞中中枢瘦素信号的作用(SS2-AR KO小鼠中没有)，我们将产生关于中枢和外周瘦素信号对骨小梁和皮质骨影响的独特数据。 公共卫生相关性：该项目对人类健康有几个应用。骨质疏松症和肥胖在社会上显著增加，了解出生前和出生后营养之间的相互作用如何影响骨骼可能有助于确定在生长过程中获得骨量和力量的潜在机制。