Connor K L, Vickers M H, Cupido C, Sirimanne E, Sloboda D M
Liggins Institute and the National Research Centre for Growth and Development, University of Auckland, Auckland, New Zealand.
J Dev Orig Health Dis. 2010 Aug;1(4):245-54. doi: 10.1017/S2040174410000346.
We previously reported that a maternal high fat (HF) diet resulted in adult offspring with increased adiposity and hyperleptinemia. As leptin has an inhibitory effect on adrenal steroidogenesis and a stimulatory effect on epinephrine synthesis, we hypothesized that key adrenal steroidogenic and catecholaminergic enzymes would be altered in these offspring. Wistar rats were randomized into three groups at weaning: (1) control dams fed a standard control chow diet from weaning and throughout pregnancy and lactation (CON), (2) dams fed a HF diet from weaning and throughout pregnancy and lactation (MHF) and (3) dams fed standard control chow diet throughout life until conception, then fed a HF diet in pregnancy and lactation (PLHF). Dams were mated at day 100 (P100). After birth at P22 (weaning), male offspring were fed a standard control chow (con) or high fat (hf) diet. At P160, plasma samples and adrenal tissues were collected. Postweaning hf diet significantly elevated plasma corticosterone concentrations in PLHF-hf offspring compared to PLHF-con. MHF nutrition increased adrenal adrenocorticotrophic hormone receptor (ACTH-R) mRNA levels compared to CON-con. 3β-hydroxysteroid dehydrogenase (3βHSD) mRNA levels were decreased in MHF compared to PLHF offspring. Phenylethanolamine N-methyltransferase (PNMT) mRNA levels were increased in MHF-hf offspring compared to MHF-con. Plasma homocysteine (HCY) concentrations were significantly elevated in CON-hf and MHF-hf offspring compared to chow-fed offspring, associated with elevated intakes of methionine and reduced intakes of pyridoxine. Immunoreactive leptin receptor (ObRb) and PNMT were colocalized in medullary chromaffin cells. This study suggests that a postweaning HF diet in offspring induced changes in adrenal gene expression levels that are dependent upon the level of maternal nutrition.
我们之前报道过,母体高脂(HF)饮食会导致成年子代肥胖增加和高瘦素血症。由于瘦素对肾上腺类固醇生成有抑制作用,对肾上腺素合成有刺激作用,我们推测这些子代中关键的肾上腺类固醇生成酶和儿茶酚胺能酶会发生改变。将Wistar大鼠在断奶时随机分为三组:(1)从断奶到整个怀孕和哺乳期均喂食标准对照饲料的对照母鼠(CON),(2)从断奶到整个怀孕和哺乳期均喂食HF饮食的母鼠(MHF),以及(3)终生喂食标准对照饲料直至受孕,然后在怀孕和哺乳期喂食HF饮食的母鼠(PLHF)。母鼠在第100天(P100)交配。在P22(断奶)出生后,雄性子代喂食标准对照饲料(con)或高脂(hf)饮食。在P160时,收集血浆样本和肾上腺组织。与PLHF-con相比,断奶后hf饮食显著提高了PLHF-hf子代的血浆皮质酮浓度。与CON-con相比,MHF营养增加了肾上腺促肾上腺皮质激素受体(ACTH-R)mRNA水平。与PLHF子代相比,MHF子代中3β-羟基类固醇脱氢酶(3βHSD)mRNA水平降低。与MHF-con相比,MHF-hf子代中苯乙醇胺N-甲基转移酶(PNMT)mRNA水平升高。与喂食普通饲料的子代相比,CON-hf和MHF-hf子代的血浆同型半胱氨酸(HCY)浓度显著升高,这与蛋氨酸摄入量增加和吡哆醇摄入量减少有关。免疫反应性瘦素受体(ObRb)和PNMT在髓质嗜铬细胞中共定位。这项研究表明,子代断奶后高脂饮食会导致肾上腺基因表达水平发生变化,这种变化取决于母体营养水平。