Gupta Anshu, Srinivasan Malathi, Thamadilok Supaporn, Patel Mulchand S
Department of Biochemistry and Pediatrics, University at Buffalo, State University of New York, Buffalo, New York 14214, USA.
J Endocrinol. 2009 Mar;200(3):293-300. doi: 10.1677/JOE-08-0429. Epub 2008 Dec 12.
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 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 agouti-related 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.
高脂（HF）饮食喂养的大鼠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。我们研究了孕期前后由高脂饮食诱导的母体肥胖对足月胎儿下丘脑瘦素和胰岛素信号传导以及促食欲和抑食欲肽表达的影响。孕期前后食用高脂饮食导致高脂雌性大鼠肥胖；此外，高脂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，在妊娠后期更为明显。高脂雌性大鼠（FHF）的足月胎儿与对照胎儿（FLC）相比，血清瘦素和胰岛素水平也显著更高，而两组胎儿的平均体重没有差异。FHF下丘脑显示瘦素长受体和胰岛素受体β亚基的mRNA和蛋白质水平升高。然而，分别作为瘦素和胰岛素信号传导下游信号成分的转录信号转导子和激活子-3以及胰岛素受体底物-2的蛋白质水平降低。此外，FHF下丘脑神经肽Y和刺鼠相关多肽的mRNA水平升高，表明高脂后代中的促食欲神经肽在足月胎儿期就已经上调。此外，高脂胎儿下丘脑前阿黑皮素原和黑皮质素受体-4的mRNA水平也升高。这些发现表明，孕期食用高脂饮食所诱导的子宫内环境改变对胎儿后期食欲调节神经肽以及瘦素和胰岛素信号传导具有潜在的编程作用。
