Sex-Dependent Programming of Glucose and Fatty Acid Metabolism in Mouse Offspring by Maternal Protein Restriction
Sex-Dependent Programming of Glucose and Fatty Acid Metabolism in Mouse Offspring by Maternal Protein Restriction
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DOI：
10.1016/j.genm.2012.01.004
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发表时间：
2012-06-01
期刊：
影响因子：
--
通讯作者：
Plosch, Torsten
中科院分区：
文献类型：
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作者：
van Straten, Esther M. E.;Bloks, Vincent W.;Plosch, Torsten
背景资料：胎儿期的营养状况影响成年后代谢综合征和心血管疾病的发生风险（代谢规划）。糖耐量受损和脂肪酸代谢失调是代谢综合征的标志。目的：建立一种代谢程序化的小鼠模型，研究妊娠期母体低蛋白饮食对成年子代糖脂代谢的性别特异性影响。方法：妊娠期C57 BL/6小鼠在整个妊娠期接受对照或低蛋白饮食（18%vs 9%酪蛋白）。雄性和雌性后代从6到22周龄接受低脂肪或高脂肪饮食。结果：通过生化和微阵列分析确定，妊娠期母体低蛋白饮食导致雌性后代对高脂肪喂养的胰岛素敏感性恶化。对照饲料喂养母鼠的雌性后代对高脂饲料诱导的代谢失调具有相对抗性。与此相反，母亲的低蛋白饮食并没有特别影响代谢参数的男性后代。在男性中，高脂肪饮食导致胰岛素不敏感，无论饮食的dams.Conclusions：我们的研究结果表明，胎儿营养不良对雄性小鼠后代的影响有限，但它确实影响了代谢反应的高脂肪饮食的女性。这些发现可能对未来代谢综合征的早期诊断和性别特异性治疗方案的发展具有影响。(Gend 2012;9：166-179）（C）2012 Elsevier HS Journals，Inc. All rights reserved.
Background: Nutritional conditions during fetal life influence the risk of the development of metabolic syndrome and cardiovascular diseases in adult life (metabolic programming). Impaired glucose tolerance and dysregulated fatty acid metabolism are hallmarks of metabolic syndrome.Objective: We aimed to establish a mouse model of metabolic programming focusing on the sex-specific effects of a maternal low-protein diet during gestation on glucose and lipid metabolism in the adult offspring.Methods: Pregnant C57BL/6 mice received a control or a low-protein diet (18% vs 9% casein) throughout gestation. Male and female offspring received a low-fat or a high-fat diet from 6 to 22 weeks of age.Results: Maternal low-protein diet during gestation led to deteriorated insulin sensitivity on high-fat feeding in female offspring, as determined by biochemical and microarray analyses. Female offspring of control diet fed dams were relatively resistant to high-fat diet induced metabolic dysregulation. In contrast, maternal low-protein diet did not specifically affect the metabolic parameters addressed in male offspring. In males, the high-fat diet led to insulin insensitivity regardless of the diet of the dam.Conclusions: Our findings show that fetal malnutrition has a limited impact on male mouse offspring, yet it does influence the metabolic response to a high-fat diet in females. These findings may have implications for future early diagnostics in metabolic syndrome and for the development of sex-specific treatment regimens. (Gend Med. 2012;9:166-179) (C) 2012 Elsevier HS Journals, Inc. All rights reserved.