1] Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071, China [2] Research Center of Food and Drug Evaluation, Wuhan University, Wuhan 430071, China.
Acta Pharmacol Sin. 2013 Dec;34(12):1526-34. doi: 10.1038/aps.2013.171. Epub 2013 Nov 25.
Prenatal nicotine exposure (PNE) alters the hypothalamic-pituitary-adrenocortical (HPA) axis-associated neuroendocrine metabolic programming in intrauterine growth retardation offspring rats. In this study we aimed to clarify the susceptibility to metabolic diseases of PNE offspring rats fed a high-fat diet.
Maternal Wistar rats were injected with nicotine (1.0 mg/kg, sc) twice per day from gestational day 11 until full-term delivery, and all pups were fed a high-fat diet after weaning and exposed to unpredictable chronic stress (UCS) during postnatal weeks 18-20. Blood samples were collected before and after chronic stress, and serum ACTH, corticosterone, glucose, insulin, total cholesterol, triglyceride and free fatty acids levels were measured. The hypothalamus, pituitary gland and liver were dissected for histological studies.
UCS significantly increased the serum ACTH, corticosterone and insulin levels as well as the insulin resistant index without changing the serum glucose, total cholesterol, triglyceride and free fatty acids levels in adult offspring rats without PNE. The body weight of PNE offspring rats presented a typical "catch-up" growth pattern. PNE not only aggravated the UCS-induced changes in the HPA axis programmed alteration (caused further increases in the serum ACTH and corticosterone levels), but also significantly changed the glucose and lipid metabolism after UCS (caused further increases in the serum glucose level and insulin resistant index, and decrease in the serum free fatty acids). The effects of PNE on the above indexes after UCS showed gender differences. Pathological studies revealed that PNE led to plenty of lipid droplets in multiple organs.
PNE enhances not only the HPA axis, but also the susceptibility to metabolic diseases in adult offspring rats fed a high-fat diet after UCS in a gender-specific manner and enhances the susceptibility to metabolic diseases in adult offspring rats fed a high-fat diet.
产前尼古丁暴露（PNE）改变宫内生长受限后代大鼠下丘脑-垂体-肾上腺皮质（HPA）轴相关神经内分泌代谢编程。本研究旨在阐明高脂肪饮食喂养的 PNE 后代大鼠易患代谢性疾病的情况。
Wistar 孕鼠从妊娠第 11 天开始每天接受两次尼古丁（1.0mg/kg，sc）注射，直至足月分娩，所有幼鼠断奶后均给予高脂肪饮食，并在产后第 18-20 周接受不可预测的慢性应激（UCS）。在慢性应激前后采集血样，检测血清 ACTH、皮质酮、血糖、胰岛素、总胆固醇、甘油三酯和游离脂肪酸水平。解剖下丘脑、垂体和肝脏进行组织学研究。
UCS 显著增加了成年无 PNE 后代大鼠的血清 ACTH、皮质酮和胰岛素水平以及胰岛素抵抗指数，而不改变血清葡萄糖、总胆固醇、甘油三酯和游离脂肪酸水平。PNE 后代大鼠的体重呈现出典型的“追赶”生长模式。PNE 不仅加重了 UCS 诱导的 HPA 轴编程改变（导致血清 ACTH 和皮质酮水平进一步升高），而且还显著改变了 UCS 后的葡萄糖和脂质代谢（导致血清葡萄糖水平和胰岛素抵抗指数进一步升高，血清游离脂肪酸水平降低）。PNE 对 UCS 后上述指标的影响存在性别差异。病理研究表明，PNE 导致多个器官中存在大量的脂质滴。
PNE 不仅增强了 HPA 轴，而且以性别特异性的方式增强了高脂肪饮食喂养的 UCS 后成年后代大鼠易患代谢性疾病的易感性，并增强了高脂肪饮食喂养的成年后代大鼠易患代谢性疾病的易感性。
