Hypothalamic alterations in fetuses of high fat diet-fed obese female rats
Hypothalamic alterations in fetuses of high fat diet-fed obese female rats
复制标题
DOI：
10.1677/joe-08-0429
复制
发表时间：
2009-03-01
影响因子：
4
通讯作者：
Patel, Mulchand S.
中科院分区：
文献类型：
--
作者：
Gupta, Anshu;Srinivasan, Malathi;Patel, Mulchand S.
高脂肪（HF）饮食喂养大鼠的后代在成年期体重增加。然而，尚不清楚这些动物食欲调节的变化是发生在子宫内还是出生后。我们研究了怀孕前和怀孕期间HF饮食诱导的产妇肥胖对胎儿下丘脑中瘦素和胰岛素信号以及厌氧肽和厌氧肽表达的影响。在怀孕前和怀孕期间食用HF饮食导致HF雌性大鼠肥胖：此外，HF雌性大鼠表现出高胰岛素血症和高瘦素血症，与喂食标准啮齿动物实验室饲料（LC）的对照雌性大鼠相比，妊娠后期的高胰岛素血症和高瘦素血症被夸大。HF雌性大鼠足月胎（FHF）的血清瘦素和胰岛素水平也明显高于对照胎（FLC），而两组的平均胎重无差异。FHF下丘脑瘦素长受体和胰岛素受体β亚基mRNA和蛋白水平升高。然而，瘦素和胰岛素信号的下游信号成分转录-3和胰岛素受体底物-2的信号转导和激活因子的蛋白水平分别下降。此外，FHF下丘脑神经肽Y和agoutii相关多肽mRNA水平升高，表明HF子代的产氧神经肽已经在足月胎儿期上调。此外，HF胎儿下丘脑中促阿片黑色素皮质素和黑色素皮质素受体-4的mRNA水平也升高。这些发现表明，HF饮食引起的宫内环境改变对胎儿后期食欲调节神经肽、瘦素和胰岛素信号的潜在编程效应。
The offspring of high fat (HF) diet-fed rats display increased body weight during adulthood. However, it is not known whether the changes, in appetite regulation in these animals occur in utero or postnatally. We investigated the effects of maternal obesity induced by a HF: diet prior to and during pregnancy on leptin and insulin signaling and the expression of orexigenic and anorexigenic peptides in term fetal hypothalami. The consumption of a HF diet prior to and during pregnancy resulted in obesity in HF female rats: additionally, HF female rats exhibited hyperinsulinemia and hyperleptinemia which were exaggerated in late gestation by compared with control female rats that Were fed a Standard rodent laboratory chow (LC). Term fetuses of HF female rats (FHF) also had significantly higher serum leptin and insulin levels compared with control fetuses (FLC) while there was no difference in average fetal weight between the two groups. FHF hypothalami showed elevated levels of mRNA and proteins for leptin long receptor and insulin receptor beta-subunit. However, the protein levels of Signal transducers and activators of transcription-3 and insulin receptor substrate-2, the downstream signaling components of leptin and insulin signaling respectively were decreased. Also, FHF hypothalami had increased mRNA levels of neuropeptide Y and agoutirelated polypeptide indicating that orexigenic neuropeptides in HF progeny are already upregulated by term fetal stage. Additionally, the mRNA levels of pro-opiatemelanocortin and melanocortin receptor-4 were also increased in the HF fetal hypothalami. These findings indicate potential programming effects of an altered intrauterine environment induced by HF diet consumption on appetite-regulating neuropeptides, and leptin and insulin signaling in the late fetal period.