Maternal and postweaning diet interaction alters hypothalamic gene expression and modulates response to a high-fat diet in male offspring
Maternal and postweaning diet interaction alters hypothalamic gene expression and modulates response to a high-fat diet in male offspring
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DOI：
10.1152/ajpregu.90585.2008
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发表时间：
2009-10-01
影响因子：
2.8
通讯作者：
Anday, Endla K.
中科院分区：
文献类型：
--
作者：
Page, Kathleen C.;Malik, Raleigh E.;Anday, Endla K.
KC页，Malik RE，Ripple JA，Anday EK。母体和断奶后的饮食相互作用改变了下丘脑基因的表达，并调节了雄性后代对高脂肪饮食的反应。Am J Physiol Regul Integr Comp Physiol 297：R1049-R1057,2009。2009年8月5日首次出版；DOI：10.1152/ajpregu.90585.2008。-流行病学数据和动物研究结果表明，母体营养失衡影响子代代谢紊乱的表现。我们测试了这样一种假设，即怀孕和哺乳期间过量饱和脂肪的摄入会导致成年代谢功能障碍，而且这些功能障碍可能会进一步受到断奶后饮食的影响。在交配、怀孕和哺乳之前，研究人员将喂食高饱和脂肪(45千卡/100千卡)饲料的成年母鸡的雄性后代与母鸡的成年雄性后代进行了比较。仔鼠断奶后开始食用标准食物或高脂肪食物。动物在禁食24小时后120天被处死。如果从断奶到成年期间喂食高脂饮食，对照组或高脂母鼠的后代体重、能量摄入量、脂肪沉积、血清瘦素和胰岛素显著高于对照组。只有从脂肪喂养的母鸡中喂养的脂肪喂养的后代才会高血糖。在孕期和成年期暴露于过量饱和脂肪的子代中，瘦素受体、前阿片黑素皮质素和神经肽Y(NPY)也显著增加，而NPY1受体下调。与对照组相比，高脂饲养组仔鼠的信号转导和转录激活因子3mRNA水平显著升高，而可卡因和安非他明调节的转录或细胞因子信号转导抑制因子3mRNA水平无明显变化，刺鼠相关蛋白表达的增加未达到显著水平。在从高脂饮食过渡到食物的后代中，观察到磷脂酰肌醇3-激酶调节亚单位(P85α)显著减少，同时蛋白激酶B上调，而在高脂饮食断奶的高脂肪后代中，P85α的表达显著增加。这些数据支持这样一种假设，即生命早期暴露于过量脂肪与下丘脑对体重和能量平衡调节的变化有关，断奶后的饮食影响代谢功能障碍和肥胖的发展。
Page KC, Malik RE, Ripple JA, Anday EK. Maternal and postweaning diet interaction alters hypothalamic gene expression and modulates response to a high-fat diet in male offspring. Am J Physiol Regul Integr Comp Physiol 297: R1049-R1057, 2009. First published August 5, 2009; doi: 10.1152/ajpregu.90585.2008.-Epidemiological data and results from animal studies indicate that imbalances in maternal nutrition impact the expression of metabolic disorders in the offspring. We tested the hypothesis that consumption of excess saturated fats during pregnancy and lactation contributes to adult metabolic dysfunction and that these disturbances can be further influenced by the postweaning diet. Adult male offspring from chow-fed dams were compared with males from dams fed a diet high in saturated fat (45 kcal/100 kcal) before mating, pregnancy, and lactation. Offspring were weaned to a standard chow diet or high fat diet. Animals were killed at 120 days after a 24-h fast. Body weight, energy intake, fat deposition, serum leptin, and insulin were significantly higher in offspring from control or high-fat dams if fed a high-fat diet from weaning to adulthood. Only fat-fed offspring from fat-fed dams were hyperglycemic. Leptin receptor, proopiomelanocortin, and neuropeptide Y (NPY) were also significantly increased in offspring exposed to excess saturated fat during gestation and into adulthood, whereas NPY1 receptor was downregulated. Signal transducer and activator of transcription 3 mRNA level was significantly higher in offspring from high-fat-fed dams compared with controls; however, no change was detected in cocaine and amphetamine-regulated transcript or suppressor of cytokine signaling 3. An increase in agouti-related protein expression did not reach significance. A significant reduction in phosphatidylinositol 3-kinase regulatory subunit (p85 alpha) coupled to an upregulation of protein kinase B was observed in offspring from high-fat-fed dams transitioned to chow food, whereas p85 alpha expression was significantly increased in high-fat offspring weaned to the high-fat diet. These data support the hypothesis that early life exposure to excess fat is associated with changes in hypothalamic regulation of body weight and energy homeostasis and that postweaning diet influences development of metabolic dysfunction and obesity.