Cortisol regulation of perinatal adipose tissue and sheep neonatal leptin peak

皮质醇对围产期脂肪组织和绵羊新生儿瘦素峰值的调节

基本信息

批准号：
9258462
负责人：
PETER W. NATHANIELSZ
金额：
$ 30万
依托单位：
UNIVERSITY OF WYOMING
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-07-15 至 2019-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9258462
关键词：
AIDS diagnosis Address Adipose tissue Adult Adult Children Affect Age Agriculture Animal Experimentation Animal Model Animals Appetite Stimulants Back Biological Biology Birth Blood Vessels Body Composition Body Weight Brain Breeding Caring Catheterization Catheters Cell Differentiation process Cell division Childhood Chronic Disease Colostrum Data Dependence Deposition Desire for food Development Diagnosis Diagnostic Diet Discipline of obstetrics Eating Economics Epidemic Equilibrium Fatty acid glycerol esters Fetus Food Glucocorticoid Receptor Glucocorticoids Glucose Goals Harvest Health Hormones Human Hydrocortisone Hypothalamic structure IGF1 gene In Vitro Infusion procedures Insulin Intake Intra-abdominal Intramuscular Laboratories Lead Leptin Life Life Cycle Stages Lipids Livestock Longevity Matched Group Meat Messenger RNA Metabolism Milk Modeling NIH Program Announcements Neonatal Nulliparity Nutrient Obesity Operative Surgical Procedures Outcome Paper Pathway interactions Pediatrics Perinatal Phenotype Plasma Play Pregnancy Prevention Procedures Production Proteins Publishing Randomized Rattus Regulation Resources Rodent Role Saline Sampling Sheep Signal Transduction Site Source Specificity Testing Therapeutic Thinness Time Tissues Triiodothyronine Weaning Weight Gain Woman Wool Work abdominal fat evidence base experience experimental study feeding fetal food quality in vivo increased appetite innovation instrumentation man maternal obesity neonate novel offspring postnatal pregnant premature prenatal programs public health relevance relating to nervous system response sex skills

项目摘要

DESCRIPTION (provided by applicant): Leptin, acts on hypothalamic appetitive centers to inhibit food intake. In neonatal, altricial rodents a postnatal day (PND) 8 - 21 leptin peak programs balance of orexigenic and anorexigenic hypothalamic centers. The peak is amplified and prolonged in obese rat offspring (OFF). No comprehensive studies on neonatal leptin exist in precocial species, humans or important farm animals. Our sheep model of diet-induced maternal obesity (MO) increases adult OFF appetite and adiposity. We have characterized the neonatal leptin peak in OFF of control (C) normally fed ewes (C-OFF) and MO-OFF and plasma cortisol, insulin, IGF1, T3 and glucose. The C-OFF leptin peak was eliminated in both F1 and F2 MO-OFF associated with higher neonatal cortisol. HYPOTHESES: 1. cortisol, the major coordinator of tissue maturation for independent post-natal life, plays a central role in perinatal adipose tissue maturation and regulation of C-OFF neonatal leptin; 2) increased MO-OFF perinatal cortisol induces premature adipose tissue maturation and eliminates the C-OFF leptin peak; 3) mimicking MO-OFF perinatal cortisol in C-OFF increases adult appetite and adiposity. We also hypothesize OFF sex specificity. APPROACH: Lean 18 month, morphometrically homogeneous, nulliparous ewes are randomly assigned as: 1) C; ewes fed 100% diet pre-, during and after pregnancy or 2) MO, ewes fed 150% diet from 60 d before breeding, during and after pregnancy. Experiments: We will study ten groups: Four fetal groups, vascular catheters placed at 127 and terminated at 147 days gestation (dG) - 1) saline infused C-fetuses; 2) saline infused MO-fetuses; 3) long term cortisol infused C-fetuses to mimic MO fetal cortisol; 4) short term cortisol infused C-fetuses from 133 dG to produce delivery in 96h. Three neonatal groups born spontaneously, studied to PND 9: 5) C-neonates given saline; 6) MO-neonates given saline; 7) Cortisol-C neonates given cortisol to mimic neonatal MO cortisol; Three adult groups, since we now show increased fetal cortisol in MO the adult studies are clearer, 8) saline infused C, 9) saline infused MO, and 10) long-term cortisol infused C, catheterized as fetuses and then studied post-natally allowed to deliver and studied from birth to PND 9, suckled, weaned, evaluated with a leptin sensitivity test and studied in a feeding challenge in adult life. Endpoint: plasma leptin, cortisol, T3, insulin, IGF1 and glucose and in vitro adipose tissue function, mRNA and protein products. RESPONSIVENESS: the sheep is the only species permitting combined full life-course studies with fetal instrumentation, responsive to the Dual Purpose, Dual Benefit goal, contributing to human obstetrics and pediatrics and an important food and wool resource. PIs bring complementary surgical and laboratory skills and experience. RELEVANCE TO THE NATION'S HEALTH AND FARM ANIMALS: We address mechanisms of perinatal cortisol action on adipose tissue to 1) in women aid diagnosis, prevention and treatment of poor MO OFF outcomes in the current human MO epidemic; 2) in sheep, provide the biological information essential to feed efficiency and meat quality.

描述（由申请人提供）：瘦素，作用于下丘脑食欲中心以抑制食物摄入量。在新生儿，唯一的啮齿动物的产后日（PND）8-21瘦素峰值程序的牙齿和厌食性下丘脑中心的平衡。在肥胖的大鼠后代（OFF）中，峰会扩大并延长峰值。在早体物种，人类或重要的农场动物中，没有关于新生儿瘦素的全面研究。我们饮食诱发的孕产妇肥胖症（MO）的绵羊模型可以增加成人的食欲和肥胖。我们已经表征了正常喂养母羊（C-OFF），MO-OFF和血浆皮质醇，胰岛素，IGF1，T3和葡萄糖的新生儿瘦素峰（C）。在与新生儿皮质醇相关的F1和F2 Mo-Oft中，消除了C-OFF瘦素峰。假设：1。皮质醇是组织成熟的主要产后生活的主要协调员，在围产期中起着核心作用脂肪组织成熟和C-Off新生儿瘦素的调节； 2）增加的MO-OFF围产期皮质醇会诱导过早的脂肪组织成熟并消除C-Off瘦素峰； 3）模仿C-OFF中的Mo-Off围产期皮质醇会增加成人的食欲和肥胖。我们还假设了性别特异性。方法：瘦18个月，形态法规均匀，无效母羊被随机分配为：1）c;母羊在怀孕期间和之后喂养100％饮食，或2）mo，母羊在繁殖前，在怀孕期间和之后的60 d饮食中喂养150％的饮食。实验：我们将研究十个组：四个胎儿组，置于127的血管导管，并在147天妊娠（DG）-1）盐水注入盐水中； 2）注入盐水的莫犬； 3）长期皮质醇注入了C-fetuses以模仿胎儿皮质醇； 4）短期皮质醇注入了133 dg的C-fetus，以96h的形式产生递送。三个新生儿自发出生，研究到PND 9：5）C-Neonates给出了盐水； 6）盐酸盐； 7）皮质醇-C新生儿将皮质醇给模仿新生儿Mo Cortisol； Three adult groups, since we now show increased fetal cortisol in MO the adult studies are clearer, 8) saline infused C, 9) saline infused MO, and 10) long-term cortisol infused C, catheterized as fetuses and then studied post-natally allowed to deliver and studied from birth to PND 9, suckled, weaned, evaluated with a leptin sensitivity test and studied in a feeding challenge in adult life.端点：血浆瘦素，皮质醇，T3，胰岛素，IGF1和葡萄糖以及体外脂肪组织功能，mRNA和蛋白质产物。响应能力：绵羊是唯一允许将完整的人生研究与胎儿仪器结合在一起的物种，对双重目的，双重收益目标，对人类的妇产科和儿科以及重要的食物和羊毛资源做出贡献。 PI带来互补的外科手术和实验室技能和经验。与国家的健康和农场动物有关：我们解决围产期皮质醇对脂肪组织作用的机制，以帮助1）妇女在当前人类MO流行病中促进诊断，预防和治疗差的MO的差异； 2）在绵羊中，为饲喂效率和肉质质量提供必不可少的生物学信息。

项目成果

期刊论文数量（8）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Cardiovascular consequences of maternal obesity throughout the lifespan in first generation sheep.

DOI：
10.1371/journal.pone.0274214
发表时间：
2022
期刊：
PLOS ONE
影响因子：
3.7
作者：
Pankey, Christopher L.;Wang, Qiurong;King, Jessica;Ford, Stephen P.
通讯作者：
Ford, Stephen P.

Effects of maternal obesity in an ovine model on metabolic outcomes in F2 adults and F3 neonates.

DOI：
10.1016/j.domaniend.2021.106628
发表时间：
2021-07
期刊：
Domestic animal endocrinology
影响因子：
2.1
作者：
Pankey CL;Odhiambo JF;Smith AM;Ford SP
通讯作者：
Ford SP

Maternal obesity in sheep impairs foetal hepatic mitochondrial respiratory chain capacity.

绵羊母体肥胖会损害胎儿肝线粒体呼吸链的能力。

DOI：
10.1111/eci.13375
发表时间：
2021
期刊：
European journal of clinical investigation
影响因子：
5.5
作者：
Serafim,TeresaL;Cunha-Oliveira,Teresa;Deus,ClaudiaM;Sardão,VilmaA;Cardoso,InesM;Yang,Shanshan;Odhiambo,JohnF;Ghnenis,AdelB;Smith,AshleyM;Li,Junfei;Nathanielsz,PeterW;Ford,StephenP;Oliveira,PauloJ
通讯作者：
Oliveira,PauloJ

Maternal obesity in the ewe increases cardiac ventricular expression of glucocorticoid receptors, proinflammatory cytokines and fibrosis in adult male offspring.