Gorski Judith N, Dunn-Meynell Ambrose A, Hartman Thomas G, Levin Barry E
Department of Neurology and Neurosciences, New Jersey Medical School, University of Medicine and Dentistry New Jersey, USA.
Am J Physiol Regul Integr Comp Physiol. 2006 Sep;291(3):R768-78. doi: 10.1152/ajpregu.00138.2006. Epub 2006 Apr 13.
There is growing evidence that the postnatal environment can have a major impact on the development of obesity and insulin resistance in offspring. We postulated that cross-fostering obesity-prone offspring to lean, obesity-resistant dams would ameliorate their development of obesity and insulin resistance, while fostering lean offspring to genetically obese dams would lead them to develop obesity and insulin resistance as adults. We found that obesity-prone pups cross-fostered to obesity-resistant dams remained obese but did improve their insulin sensitivity as adults. In contrast, obesity-resistant pups cross-fostered to genetically obese dams showed a diet-induced increase in adiposity, reduced insulin sensitivity, and associated changes in hypothalamic neuropeptide, insulin, and leptin receptors, which might have contributed to their metabolic defects. There was a selective increase in insulin levels and differences in fatty acid composition of obese dam milk which might have contributed to the increased adiposity, insulin resistance, and hypothalamic changes in obesity-resistant cross-fostered offspring. These results demonstrate that postnatal factors can overcome both genetic predisposition and prenatal factors in determining the development of adiposity, insulin sensitivity, and the brain pathways that mediate these functions.
越来越多的证据表明，产后环境会对后代肥胖和胰岛素抵抗的发展产生重大影响。我们推测，将易肥胖的后代与瘦的、抗肥胖的母鼠进行交叉寄养，会改善它们肥胖和胰岛素抵抗的发展，而将瘦的后代寄养到遗传性肥胖的母鼠那里，会导致它们成年后出现肥胖和胰岛素抵抗。我们发现，易肥胖的幼崽被寄养到抗肥胖的母鼠那里后，成年后仍然肥胖，但胰岛素敏感性确实有所改善。相比之下，被寄养到遗传性肥胖母鼠那里的抗肥胖幼崽，出现了饮食诱导的肥胖增加、胰岛素敏感性降低，以及下丘脑神经肽、胰岛素和瘦素受体的相关变化，这些变化可能导致了它们的代谢缺陷。肥胖母鼠的乳汁中胰岛素水平有选择性地升高，脂肪酸组成也存在差异，这可能导致了抗肥胖交叉寄养后代的肥胖增加、胰岛素抵抗和下丘脑变化。这些结果表明，在决定肥胖、胰岛素敏感性以及介导这些功能的脑通路的发展过程中，产后因素可以克服遗传易感性和产前因素。
