Department of Food Science and Human Nutrition, and Division of Nutritional Sciences, University of Illinois at Urbana-Champaign, 461 Bevier Hall, MC-182, 905 South Goodwin Avenue, Urbana, IL 61801, USA.
J Physiol. 2011 Jun 1;589(Pt 11):2707-17. doi: 10.1113/jphysiol.2010.203950. Epub 2011 Mar 28.
In insulin resistance and type II diabetes, there is an elevation of hepatic gluconeogenesis, which contributes to hyperglycaemia. Studies in experimental animals have provided evidence that consumption of high fat (HF) diets by female rats programs the progeny for glucose intolerance in adulthood, but the mechanisms behind the in utero programming remain poorly understood. The present study analysed the effect of a maternal HF diet on fetal gluconeogenic gene expression and potential regulation mechanism related to histone modifications. Dams were fed either a Control (C, 16% kcal fat) or a high-fat (HF, 45% kcal fat) diet throughout gestation. Livers of the offspring were collected on gestational day 21 and analysed to determine the consequences of a maternal HF diet on molecular markers of fetal liver gluconeogenesis. We demonstrated that offspring of HF-fed dams were significantly heavier and had significantly higher blood glucose levels at the time of delivery than offspring of dams fed the C diet. While maternal gluconeogenesis and plasma glucose were not affected by the HF diet, offspring of HF-fed dams had significantly higher mRNA contents of gluconeogenic genes in addition to the elevated plasma glucose. In addition to increased transcription rate, a gestational HF diet resulted in modifications of the Pck1 histone code in livers of offspring. Our results demonstrate that in utero exposure to HF diet has the potential to program the gluconeogenic capacity of offspring through epigenetic modifications, which could potentially lead to excessive glucose production and altered insulin sensitivity in adulthood.
在胰岛素抵抗和 2 型糖尿病中，肝脏糖异生升高，导致高血糖。实验动物研究提供的证据表明，雌性大鼠高脂肪（HF）饮食会使后代在成年后出现葡萄糖耐量异常，但宫内编程的机制仍知之甚少。本研究分析了母体 HF 饮食对胎儿糖异生基因表达的影响及其与组蛋白修饰相关的潜在调节机制。在整个妊娠期，母鼠分别喂食对照（C，16%热量脂肪）或高脂肪（HF，45%热量脂肪）饮食。在妊娠第 21 天收集后代的肝脏，并分析母体 HF 饮食对胎儿肝脏糖异生分子标志物的影响。我们发现，与喂食 C 饮食的母鼠的后代相比，喂食 HF 饮食的母鼠的后代体重明显增加，分娩时血糖水平明显升高。虽然母体糖异生和血浆葡萄糖不受 HF 饮食的影响，但喂食 HF 饮食的母鼠的后代的糖异生基因的 mRNA 含量明显更高，同时血浆葡萄糖也升高。除了转录率增加外，妊娠期 HF 饮食还导致后代肝脏中 Pck1 组蛋白密码发生改变。我们的研究结果表明，宫内暴露于 HF 饮食有可能通过表观遗传修饰来调节后代的糖异生能力，这可能导致成年后葡萄糖过度产生和胰岛素敏感性改变。
