Sex-specific effects of prenatal stress on glucose homoeostasis and peripheral metabolism in rats
Sex-specific effects of prenatal stress on glucose homoeostasis and peripheral metabolism in rats
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DOI：
10.1530/joe-12-0540
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发表时间：
2013-05-01
影响因子：
4
通讯作者：
Drake, Amanda J.
中科院分区：
文献类型：
--
作者：
Brunton, Paula J.;Sullivan, Katie M.;Drake, Amanda J.
怀孕期间糖皮质激素过度暴露会影响后代的生理机能，并导致以后患病。然而，与行为学相关的母亲压力的影响尚不清楚，但具有生理重要性。在这里，我们在大鼠中研究了妊娠后期重复的社会压力（暴露于攻击性哺乳期雌性）对成年后代的短期和长期影响，这些压力对应激后的葡萄糖调节、葡萄糖-胰岛素稳态以及对调节葡萄糖和脂质代谢以及糖皮质激素作用重要的基因的外周表达产生影响。产前应激（PNS）与女性后代出生体重下降有关，但与男性后代无关。与对照组相比，成年三七总皂甙男性的血糖在抑制下的增加被夸大，但在女性中则不然。口服葡萄糖耐量测试显示 3 个月时对任一性别的血浆葡萄糖或胰岛素浓度均无影响；然而，在 6 个月时，PNS 雌性在口服葡萄糖负荷后出现高胰岛素血症。在 PNS 男性中，血浆甘油三酯浓度升高，5 α 还原酶和过氧化物酶体增殖物激活受体 α (Ppar α (Ppara)) 的肝脏 mRNA 表达减少，并且过氧化物酶体增殖物激活受体 γ 共激活物 1 α (Pgc1 α (Ppargc1a)) 和 Ppar gamma (Pparg) 表达，而在 PNS 雌性中只有 Pgc1 α mRNA 受到影响。相反，在皮下脂肪中，PNS 降低女性皮下脂肪中 11 β-羟基类固醇脱氢酶 1 型 (11 β hsd1)、磷酸烯醇丙酮酸羧激酶 (Pepck (Pck1))、脂肪甘油三酯脂肪酶 (Atgl) 和甘油二酯酰基转移酶 2 (Dgat2) 的 mRNA 表达，但仅限于女性 Pepck mRNA 表达在 PNS 男性中降低。因此，产前社会压力对雄性和雌性后代的葡萄糖稳态和外周代谢有不同的影响。这些生理学的长期改变可能会增加对代谢疾病的易感性。
Glucocorticoid overexposure during pregnancy programmes offspring physiology and predisposes to later disease. However, any impact of ethologically relevant maternal stress is less clear, yet of physiological importance. Here, we investigated in rats the short- and long-term effects in adult offspring of repeated social stress (exposure to an aggressive lactating female) during late pregnancy on glucose regulation following stress, glucose-insulin homoeostasis and peripheral expression of genes important in regulating glucose and lipid metabolism and glucocorticoid action. Prenatal stress (PNS) was associated with reduced birth weight in female, but not male, offspring. The increase in blood glucose with restraint was exaggerated in adult PNS males compared with controls, but not in females. Oral glucose tolerance testing showed no effects on plasma glucose or insulin concentrations in either sex at 3 months; however, at 6 months, PNS females were hyperinsulinaemic following an oral glucose load. In PNS males, plasma triglyceride concentrations were increased, with reduced hepatic mRNA expression of 5 alpha-reductase and peroxisome proliferator-activated receptor alpha (Ppar alpha (Ppara)) and a strong trend towards reduced peroxisome proliferator-activated receptor gamma coactivator 1 alpha (Pgc1 alpha (Ppargc1a)) and Ppar gamma (Pparg) expression, whereas only Pgc1 alpha mRNA was affected in PNS females. Conversely, in subcutaneous fat, PNS reduced mRNA expression of 11 beta-hydroxysteroid dehydrogenase type 1 (11 beta hsd1), phosphoenolpyruvate carboxykinase (Pepck (Pck1)), adipose triglyceride lipase (Atgl) and diglyceride acyltransferase 2 (Dgat2) in females, but only Pepck mRNA expression was reduced in PNS males. Thus, prenatal social stress differentially programmes glucose homoeostasis and peripheral metabolism in male and female offspring. These long-term alterations in physiology may increase susceptibility to metabolic disease.