Fostering in mice induces cardiovascular and metabolic dysfunction in adulthood

Fostering in mice induces cardiovascular and metabolic dysfunction in adulthood
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DOI:
10.1113/jphysiol.2011.212324
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发表时间:
2011-08-15
影响因子:
5.5
通讯作者:
Taylor, Paul D.
Taylor, Paul D.
中科院分区:
医学1区
文献类型:
--
作者:
Matthews, Phillippa A.;Samuelsson, Anne-Maj;Taylor, Paul D.

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交叉养育被广泛应用于发育规划研究,以确定子宫内和哺乳时期在建立成体后代表型以应对环境挑战方面的相对贡献。我们研究了饲养过程本身是否影响成年C57BL/6J小鼠后代的心血管和代谢功能,并与它们的生物坝哺育的动物进行了比较。交叉饲养(CF)小鼠表现出幼年发病的吞噬功能和显著增加的体重(从断奶到12周:雄性对照组与CF:P<0.01,雌性CON与CF:P<0.001;RM ANOVA),并仅在雄性中伴随腹部脂肪增加(白色脂肪组织质量(Mg):CON 280.5+/-13.4[Mean+/-SEM](n=7)vs CF,549.8+/-99.3(n=8),P<0.01)。雄性和雌性CF小鼠均表现出显著的糖耐量增强。雄性CF小鼠的收缩压显著升高(白天:CON 100.5+/-1.41(n=6)vs CF 114.3+/-0.7vs.108.0+/-2.0vs.CF123.2+/-0.001(n=6),P<0.001)。雄性CFs小鼠内皮依赖性舒张功能增强,雌性CFs小鼠肾脏去甲肾上腺素升高。CF组血清甘油三酯、胆固醇、胰岛素和瘦素水平明显高于CON组。交叉培养的过程深刻地影响了小鼠的心血管和代谢表型。这一发现对将适当的对照纳入未来研究的设计和解释先前在小鼠身上进行的交叉培养研究具有重要意义。
Cross-fostering is widely used in developmental programming studies to determine the relative contribution of the in utero and suckling periods in establishing the adult offspring phenotype in response to an environmental challenge. We have investigated whether the process of fostering per se influences cardiovascular and metabolic function in adult offspring of C57BL/6J mice in comparison with animals suckled by their biological dams. Cross-fostered (CF) mice demonstrated juvenile onset hyperphagia and significantly higher body weight (from weaning to 12 weeks: male control (CON) vs. CF: P < 0.01, female CON vs. CF: P < 0.001; RM ANOVA) accompanied by increased abdominal adiposity in males only (white adipose tissue mass (mg): CON 280.5 +/- 13.4 [mean +/- SEM] (n = 7) vs. CF, 549.8 +/- 99.3 (n = 8), P < 0.01). Both male and female CF mice demonstrated significantly enhanced glucose tolerance. A marked increase in systolic blood pressure (SBP) was observed in male CF mice (SBP (mmHg), day: CON 100.5 +/- 1.4 (n = 6) vs. CF 114.3 +/- 0.7 (n = 6), P < 0.001; night: CON 108.0 +/- 2.0 (n = 6) vs. CF 123.2 +/- 1.1 (n = 6), P < 0.001). Endothelium-dependent relaxation was enhanced in male CFmice, and renal noradrenaline was increased in female CF mice. Concentration of serum triglycerides, cholesterol, insulin and leptin were increased in CF vs. CON. The process of cross-fostering profoundly affects cardiovascular and metabolic phenotype in mice. The findings have implications for the inclusion of appropriate controls in the design of future studies and in the interpretation of previous cross-fostering studies in mice.