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高能饮食和肥胖多基因易感性对大鼠母鼠产后健康的影响。

Influence of High Energy Diet and Polygenic Predisposition for Obesity on Postpartum Health in Rat Dams.

作者信息

Leuthardt Andrea S, Bayer Julia, Monné Rodríguez Josep M, Boyle Christina N

机构信息

Institute of Veterinary Physiology, Vetsuisse Faculty, University of Zurich, Zurich, Switzerland.

Laboratory for Animal Model Pathology (LAMP), Institute of Veterinary Pathology, Vetsuisse Faculty, University of Zurich, Zurich, Switzerland.

出版信息

Front Physiol. 2022 Feb 10;12:772707. doi: 10.3389/fphys.2021.772707. eCollection 2021.

Abstract

It is estimated that 30% of pregnant women worldwide are overweight or obese, leading to adverse health effects for both mother and child. Women with obesity during pregnancy are at higher risk for developing both metabolic and mental disorders, such as diabetes and depression. Numerous studies have used rodent models of maternal obesity to understand its consequences on the offspring, yet characterization of changes in the dams is rare, and most rodent models rely solely on a high fat diet to induce maternal obesity, without regarding genetic propensity for obesity. Here we present the influence of both peripartum high energy diet (HE) and obesity-proneness on maternal health using selectively bred diet-resistant (DR) and diet-induced obese (DIO) rat dams. Outbred Sprague-Dawley rats were challenged with HE diet prior to mating and bred according to their propensity to gain weight. The original outbred breeding dams (F0) were maintained on low-fat chow during pregnancy and lactation. By comparison, the F1 dams consuming HE diet during pregnancy and lactation displayed higher gestational body weight gain ( < 0.01), and HE diet caused increased meal size and reduced meal frequency ( < 0.001). Sensitivity to the hormone amylin was preserved during pregnancy, regardless of diet. After several rounds of selective breeding, DIO and DR dams from generation F3 were provided chow or HE during pregnancy and lactation and assessed for their postpartum physiology and behaviors. We observed strong diet and phenotype effects on gestational weight gain, with DIO-HE dams gaining 119% more weight than DR-chow ( < 0.001). A high-resolution analysis of maternal behaviors did not detect main effects of diet or phenotype, but a subset of DIO dams showed delayed nursing behavior ( < 0.05). In generation F6/F7 dams, effects on gestational weight gain persisted ( < 0.01), and we observed a main effect of phenotype during a sucrose preference test ( < 0.05), with DIO-chow dams showing lower sucrose preference than DR controls ( < 0.05). Both DIO and DR dams consuming HE diet had hepatic steatosis ( < 0.001) and exhibited reduced leptin sensitivity in the arcuate nucleus ( < 0.001). These data demonstrate that both diet and genetic obesity-proneness have consequences on maternal health.

摘要

据估计,全球30%的孕妇超重或肥胖,这对母亲和孩子都会产生不良健康影响。孕期肥胖的女性患代谢和精神疾病(如糖尿病和抑郁症)的风险更高。许多研究使用母体肥胖的啮齿动物模型来了解其对后代的影响,但对母鼠变化的特征描述很少见,而且大多数啮齿动物模型仅依靠高脂肪饮食来诱导母体肥胖,而不考虑肥胖的遗传倾向。在这里,我们使用选择性培育的抗饮食诱导肥胖(DR)和饮食诱导肥胖(DIO)大鼠母鼠,展示围产期高能饮食(HE)和肥胖倾向对母体健康的影响。远交系斯普拉格-道利大鼠在交配前接受高能饮食挑战,并根据其体重增加倾向进行繁殖。原始的远交系繁殖母鼠(F0)在怀孕和哺乳期间维持低脂食物喂养。相比之下,在怀孕和哺乳期间食用高能饮食的F1母鼠孕期体重增加更高(<0.01),高能饮食导致进食量增加和进食频率降低(<0.001)。孕期对激素胰淀素的敏感性不受饮食影响而得以保留。经过几轮选择性繁殖后,来自F3代的DIO和DR母鼠在怀孕和哺乳期间分别给予普通食物或高能饮食,并评估其产后生理和行为。我们观察到饮食和表型对孕期体重增加有强烈影响,DIO-HE母鼠比DR-普通食物组母鼠体重多增加119%(<0.001)。对母体行为的高分辨率分析未检测到饮食或表型的主要影响,但一部分DIO母鼠表现出哺乳行为延迟(<0.05)。在F6/F7代母鼠中,对孕期体重增加的影响仍然存在(<0.01),并且我们在蔗糖偏好试验中观察到表型的主要影响(<(此处原文可能有误,推测为<0.05)),DIO-普通食物组母鼠的蔗糖偏好低于DR对照组(<0.05)。食用高能饮食的DIO和DR母鼠均出现肝脂肪变性(<0.001),并且在弓状核中表现出瘦素敏感性降低(<0.001)。这些数据表明,饮食和遗传肥胖倾向都会对母体健康产生影响。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/19ea/8867007/9dac3d107ef3/fphys-12-772707-g001.jpg

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