Maternal and Postnatal Overnutrition Differentially Impact Appetite Regulators and Fuel Metabolism
Maternal and Postnatal Overnutrition Differentially Impact Appetite Regulators and Fuel Metabolism
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DOI：
10.1210/en.2008-0582
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发表时间：
2008-11-01
期刊：
影响因子：
4.8
通讯作者：
Morris, Margaret J.
中科院分区：
文献类型：
--
作者：
Chen, Hui;Simar, David;Morris, Margaret J.
母亲肥胖正在增加，并且已知宫内经历规划胎儿和新生儿代谢。然而，产前或产后因素的相对贡献是未知的。我们假设，母亲营养过剩造成的长期母亲肥胖会产生更强的不利影响比产后营养过剩对后代代谢稳态，与额外的产后营养过剩夸大这些变化。雌性Sprague道利大鼠在交配前以及整个妊娠期和哺乳期暴露于普通饲料或高脂肪自助餐5周。在出生后第1天，将窝调整为每窝3只，以诱导出生后营养过剩（对照组为12只）。下丘脑食欲调节神经肽Y和阿黑皮素原，葡萄糖转运蛋白4和脂质代谢标志物进行了测量。在出生后第20天，肥胖母鼠或出生后营养过剩母鼠所生的雄性幼崽比对照组重42%;两种干预措施相结合导致体重增加80%。母亲肥胖增加幼犬肥胖，并导致后代葡萄糖耐受不良，这些被夸大了额外的产后营养过剩在哺乳期。母亲肥胖也与后代的高脂血症和下丘脑神经肽Y减少和阿黑皮素原mRNA表达增加有关。出生后营养过剩的后代从肥胖的母鼠放大了这些下丘脑的变化。母亲和产后营养过剩减少肌肉葡萄糖转运蛋白4。脂肪肉毒碱棕榈酰转移酶-1和脂肪甘油三酯脂肪酶mRNA的上调，只有出生后营养过剩。母亲营养过剩似乎改变了中枢食欲回路，促进早发性肥胖;产后营养过剩相互作用，导致外周脂质和葡萄糖代谢紊乱，支持减少生命早期不良营养影响的关键信息。（内分泌学149：5348-5356，2008）
Maternal obesity is increasing, and it is known that the intrauterine experience programs fetal and newborn metabolism. However, the relative contributions of pre- or postnatal factors are unknown. We hypothesized that maternal overnutrition caused by long-term maternal obesity would exert a stronger detrimental impact than postnatal overnutrition on offspring metabolic homeostasis, with additional postnatal overnutrition exaggerating these alterations. Female Sprague Dawley rats were exposed to chow or high-fat cafeteria diet for 5 wk before mating and throughout gestation and lactation. On postnatal d 1, litters were adjusted to three per litter to induce postnatal overnutrition (vs. 12 in control). Hypothalamic appetite regulators neuropeptide Y and proopiomelanocortin, glucose transporter 4, and lipid metabolic markers were measured. At postnatal d 20, male pups born of obese dams, or those overnourished postnatally, were 42% heavier than controls; combining both interventions led to 80% greater body weight. Maternal obesity increased pup adiposity and led to glucose intolerance in offspring; these were exaggerated by additional postnatal overnutrition during lactation. Maternal obesity was also linked to hyperlipidemia in offspring and reduced hypothalamic neuropeptide Y and increased proopiomelanocortin mRNA expression. Postnatal overnutrition of offspring from obese dams amplified these hypothalamic changes. Both maternal and postnatal overnutrition reduced muscle glucose transporter 4. Adipose carnitine palmitoyl-transferase-1 and adipose triglyceride lipase mRNA was up-regulated only by postnatal overnutrition. Maternal overnutrition appears to alter central appetite circuits and promotes early-onset obesity; postnatal overnutrition interacted to cause peripheral lipid and glucose metabolic disorders, supporting the critical message to reduce early-life adverse nutritional impact. (Endocrinology 149: 5348-5356, 2008)