Prenatal exposure to high-fat diets promotes alcohol preference in the offspring

产前接触高脂肪饮食会促进后代对酒精的偏好

基本信息

批准号：
8320773
负责人：
Miriam E. Bocarsly
金额：
$ 2.69万
依托单位：
PRINCETON UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-09-20 至 2013-02-01
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8320773
关键词：
Accounting Address Adolescence Adolescent Adult Adult Children Age Alcohol abuse Alcohol consumption Alcohols Animal Model Animals Automobile Driving Avidity Behavior Behavioral Behavioral Model Biological Assay Birth Blood Body Weight Cells Consumption Data Diet Dietary Component Dietary Fats Dietary intake Eating Equilibrium Estrogens Ethanol Etiology Exhibits Exposure to Fatty acid glycerol esters Female Female Adolescents Fructose Galanin Gonadal Steroid Hormones Heavy Drinking Hormones Hydrolysis Hyperlipidemia Hypertriglyceridemia Hypothalamic structure In Situ Hybridization Individual Injection of therapeutic agent Intake Laboratory Finding Lead Life Link Macronutrients Nutrition Measures Messenger RNA Mothers Ovarian hormone Peptides Physiological Pregnancy Prenatal care Prevention Production Progesterone Puberty Radioimmunoassay Rat-1 Rattus Risk Factors Role Serum Site Steroids System Testing Training Triglycerides Water alcohol abuse therapy alcohol measurement alcohol preferring rats alcohol seeking behavior drinking fast food feeding fetal fetal programming improved in utero male neural circuit neurochemistry neurogenesis next generation novel offspring peptide hormone postnatal preference pregnant prenatal prenatal exposure prevent programs public health relevance pup sex trend underage drinking

项目摘要

DESCRIPTION (provided by applicant): Recent studies indicate that excessive fat intake by pregnant dams can lead to offspring that exhibit hyperlipidemia, increased food intake, preference for fat, and higher body weight. These long-term physiological and behavioral changes are driven, in part, by increased postnatal neurogenesis of galanin- expressing cells and expression of peptides that stimulate the intake of fat. These same peptides have been linked to increased alcohol intake. It follows, therefore, that these hypothalamic changes in the offspring of fat- consuming dams might create an avidity for alcohol. Here, we propose to study the effects on prenatal exposure to high-fat diet on alcohol consumption in the offspring. This will be done by (Exp.1) replicating preliminary results indicating that adolescent females, with prenatal exposure to a high-fat diet, consume significantly more alcohol than controls. This finding will be extended to males and adult offspring. Profiling age and sex specific trends in alcohol intake among animals born to fat-consuming mothers will allow us to characterize a new animal model of alcohol preferring rat. Once we have characterized this behavioral model, we will (Exp. 2) explore aberrations in peptides and sex hormones that might be driving the phenomena. We know of a neural circuit that evolved with the capability to augment fat intake; moreover, it can be co-opted by alcohol. It is also clear that drinking ethanol can increase expression of the peptides in this circuit. Therefore the new question is whether pups born to fat-consuming dams, and therefore growing up with additional hypothalamic cells producing elevated levels of orexigenic peptides, will stimulate expression of these peptides even further by drinking ethanol. This could create a triple threat for alcohol abuse: triple in the sense that the rats have, more galanin cells due to in utero programming, more galanin expression due to hormones at puberty and more galanin expression when they start drinking. Exp. 2 will address the roles of peptides and hormones underlying the behaviors seen in Exp. 1. Lastly, studies indicate that elevated triglycerides (TG) during gestation might be responsible for the behavior seen in Exp. 1 and the physiological changes seen in Exp. 2. Consumption of a high-fat diet raises TG in pregnant dams, which leads to elevated TG in the pups. This elevation of TG increases expression of fat-stimulating peptides that drive excessive intake of alcohol. Our laboratory finds that animals maintained on a diet with free access to high-fructose corn syrup show significantly elevated TG levels, as compared to controls. Therefore (Exp. 3), high dietary fructose might lead to elevated intake of alcohol in the offspring. The translational implications of prenatal dietary intake on alcohol consumption are vast. In the current "fast food" culture, mothers might be programming their offspring with a propensity for alcohol abuse. Through understanding the causation, as well as the mechanism of alcohol prone behavior, we will be better able to advise in optimal prenatal care, as well as prevention and treatment for alcohol-prone individuals. PUBLIC HEALTH RELEVANCE: In a new discovery, we find that a high-fat diet during pregnancy can program the female offspring to consume excessive amounts of alcohol during adolescence. In this proposal, the applicant plans to elucidate the mechanism of this fetal programming and its expression as a function of sex hormones, peptides and age, as well as comparing both females and males. Further, these findings will be applied to prenatal exposure of other common macronutrients, such as those found in high-fructose corn syrup. Understanding the cause and mechanism of gestational diet-induced, alcohol preference will improve prenatal care with the aim of preventing destructive, alcohol prone behavior in the next generation.

描述（由申请人提供）：最近的研究表明，怀孕的大坝过多的脂肪摄入会导致后代表现出高脂血症，食物摄入量增加，对脂肪的偏爱和体重更高。这些长期的生理和行为变化部分是由于加拉蛋白表达细胞的产后神经发生以及刺激脂肪摄入的肽的表达而驱动的。这些相同的肽与酒精摄入量增加有关。因此，因此，这些下丘脑的下丘脑变化可能会使酒精饮酒产生亲和力。在这里，我们建议研究对产前暴露于高脂饮食对后代饮酒的影响。这将通过（exp.1）复制初步结果来完成，这表明青少年女性在产前暴露于高脂饮食中，饮酒量明显高于对照。这一发现将扩展到男性和成人后代。在脂肪耗费的母亲出生的动物中，饮酒的年龄和性别特异性趋势将使我们能够表征出一种新的酒精饮食模型。一旦我们表征了这种行为模型，我们将（exp。2）探索可能推动现象的肽和性激素的像差。我们知道，随着能力增强脂肪摄入的能力而演变的神经回路。此外，它可以被酒精采用。同样很明显，饮用乙醇可以增加该电路中肽的表达。因此，新的问题是，脂肪耗尽的大坝出生的幼崽，因此长大的下丘脑细胞长大，产生升高水平的甲醇的甲醇表达，从而刺激这些肽的表达。这可能会对酒精滥用造成三重威胁：三重威胁在于大鼠具有更多的甘丙蛋白细胞，由于子宫内编程，由于青春期中的激素而引起的激素表达更多，而在开始饮用时的表达则更多。经验。 2将解决EXP中所见行为的肽和激素的作用。 1。最后，研究表明，妊娠期间甘油三酸酯（TG）的升高可能是对EXP中看到的行为的原因。 1和Exp中看到的生理变化。 2。消费高脂饮食会在怀孕的大坝中提高TG，从而导致幼犬的TG升高。 TG的这种升高增加了刺激脂肪摄入过多的酒精摄入量的脂肪刺激的表达。我们的实验室发现，与对照组相比，自由获取高果糖玉米糖浆的动物保持了高果糖玉米糖浆的水平显着升高。因此（3），高饮食果糖可能导致后代饮酒的摄入量升高。产前饮食对饮酒的转化含义是广泛的。在当前的“快餐”文化中，母亲可能正在用滥用酒精的倾向来编程后代。通过了解因果关系以及易于酒精行为的机制，我们将能够更好地提供最佳的产前护理，并为易酒精的个体提供预防和治疗。公共卫生相关性：在一个新发现中，我们发现怀孕期间的高脂饮食可以编程女性后代以在青春期食用过量的酒精。在此提案中，申请人计划阐明该胎儿编程的机制及其表达与性激素，肽和年龄的函数，并比较女性和男性。此外，这些发现将应用于其他常见大量营养素的产前暴露，例如在高果糖玉米糖浆中发现的大量营养素。了解妊娠饮食引起的饮酒偏好的原因和机制将改善产前护理，以防止下一代破坏性，易于酒精行为。