Intrauterine growth restriction (IUGR) results in dysregulated glucose homeostasis and adiposity in the adult. We hypothesized that with aging, these perturbations will wane, and superimposition of postnatal growth restriction (PNGR) on IUGR [intrauterine and postnatal growth restriction (IPGR)] will reverse the residual IUGR phenotype. We therefore undertook hyperinsulinemic-euglycemic clamp, energy balance, and physical activity studies during fed, fasted, and refed states, in light and dark cycles, on postweaned chow diet-fed more than 17-month aging male IUGR, PNGR, and IPGR vs. control (CON) rat offspring. Hyperinsulinemic-euglycemic clamp revealed similar whole-body insulin sensitivity and physical activity in the nonobese IUGR vs. CON, despite reduced heat production and energy expenditure. Compared with CON and IUGR, IPGR mimicking PNGR was lean and growth restricted with increased physical activity, O(2) consumption (VO(2)), energy intake, and expenditure. Although insulin sensitivity was no different in IPGR and PNGR, skeletal muscle insulin-induced glucose uptake was enhanced. This presentation proved protective against the chronologically earlier (5.5 months) development of obesity and dysregulated energy homeostasis after 19 wk on a postweaned high-fat diet. This protective role of PNGR on the metabolic IUGR phenotype needs future fine tuning aimed at minimizing unintended consequences.

译文

宫内生长受限 (IUGR) 导致成人葡萄糖稳态失调和肥胖。我们假设随着年龄的增长,这些扰动将减弱,并且产后生长限制 (PNGR) 对IUGR [宫内和产后生长限制 (IPGR)] 的叠加将逆转残留的IUGR表型。因此,我们对断奶后饮食喂养超过17个月的雄性IUGR,PNGR和IPGR与对照 (CON) 大鼠后代进行了高胰岛素血症-正常血糖钳夹,能量平衡和体力活动研究。尽管热量产生和能量消耗减少,但高胰岛素-正常血糖钳夹在非肥胖IUGR与CON中显示出相似的全身胰岛素敏感性和身体活动。与CON和IUGR相比,模仿PNGR的IPGR是瘦弱的,并且生长受到体力活动,O(2) 消耗 (VO(2)),能量摄入和支出增加的限制。尽管IPGR和PNGR的胰岛素敏感性没有不同,但骨骼肌胰岛素诱导的葡萄糖摄取增强。该报告证明对断奶后高脂饮食19周后肥胖的时间较早 (5.5个月) 和能量稳态失调具有保护作用。PNGR对代谢IUGR表型的这种保护作用需要未来的微调,以最大程度地减少意外后果。

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