Translational Experimental Pediatrics - Experimental Pulmonology, Department of Pediatric and Adolescent Medicine, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany.
Faculty of Medicine and University Hospital Cologne, Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany.
Clin Transl Sci. 2020 Nov;13(6):1065-1070. doi: 10.1111/cts.12811. Epub 2020 Jun 29.
Perinatal nutritional determinants known as metabolic programming could be either detrimental or protective. Maternal obesity in the perinatal period determines susceptibility for diseases, such as obesity, metabolic disorders, and lung disease. Although this adverse metabolic programming is well-recognized, the critical developmental window for susceptibility risk remains elusive. Thus, we aimed to define the vulnerable window for impaired lung function after maternal obesity; and to test if dietary intervention protects. First, we studied the impact of high-fat diet (HFD)-induced maternal obesity during intrauterine (HFD ), postnatal (HFD ), or perinatal (i.e., intrauterine and postnatal (HFD ) phase on body weight, white adipose tissue (WAT), glucose tolerance, and airway resistance. Although HFD , HFD , and HFD induced overweight in the offspring, only HFD and HFD led to increased WAT in the offspring early in life. This early-onset adiposity was linked to impaired glucose tolerance in HFD -offspring. Interestingly, these metabolic findings in HFD -offspring, but not in HFD -offspring and HFD -offspring, were linked to persistent adiposity and increased airway resistance later in life. Second, we tested if the withdrawal of a HFD immediately after conception protects from early-onset metabolic changes by maternal obesity. Indeed, we found a protection from early-onset overweight, but not from impaired glucose tolerance and increased airway resistance. Our study identified critical windows for metabolic programming of susceptibility to impaired lung function, highlighting thereby windows of opportunity for prevention.
围产期营养决定因素，即代谢编程，可能有害也可能有益。围产期母体肥胖决定了肥胖、代谢紊乱和肺部疾病等疾病的易感性。尽管这种不良的代谢编程已得到充分认识，但易感性风险的关键发育窗口仍然难以捉摸。因此，我们旨在确定母体肥胖后肺功能受损的脆弱窗口，并测试饮食干预是否具有保护作用。首先，我们研究了高脂肪饮食（HFD）诱导的围产期母体肥胖（HFD）、产后（HFD）或围产期（即宫内和产后（HFD）阶段）对体重、白色脂肪组织（WAT）、葡萄糖耐量和气道阻力的影响。尽管 HFD、HFD 和 HFD 导致后代超重，但只有 HFD 和 HFD 导致后代生命早期 WAT 增加。这种早发肥胖与 HFD 后代的葡萄糖耐量受损有关。有趣的是，这些 HFD 后代的代谢发现，而不是 HFD 后代和 HFD 后代的代谢发现，与生命后期持续肥胖和气道阻力增加有关。其次，我们测试了在受孕后立即停止 HFD 是否可以通过母体肥胖来保护免受早发代谢变化的影响。事实上，我们发现可以预防早发超重，但不能预防葡萄糖耐量受损和气道阻力增加。我们的研究确定了代谢编程易感性受损肺功能的关键窗口，从而为预防提供了机会窗口。
