Centre for Hepatology, University College London, Royal Free Hospital, London NW3 2PF, UK.
Biochem Biophys Res Commun. 2010 Mar 26;394(1):24-8. doi: 10.1016/j.bbrc.2010.02.057. Epub 2010 Feb 17.
The prevalence of pancreatic adenocarcinoma (PAC) parallels rising rates of obesity and dysmetabolism, a possible link being non-alcoholic fatty pancreas disease (NAFPD). We have recently shown that maternal obesity programmes the development of a dysmetabolic and fatty liver (non-alcoholic fatty liver disease, NAFLD) phenotype in adult offspring. Since the pancreas and liver originate from the same embryonic bud, it is plausible that maternal obesity may similarly programme the development of NAFPD. Our objective was to determine the effect of maternal obesity on development of NAFPD in offspring and ascertain contributions of the intra/extra-uterine periods.
Female C57BL/6J mice were fed either a standard chow (3% fat, 7% sugar) or a hypercalorific diet (16% fat, 33% sugar) for six weeks prior to mating and throughout pregnancy and lactation. Female offspring were cross-fostered for suckling to dams on the same or opposite diet to yield four groups: offspring of lean suckled by lean dams (n=6), offspring of obese suckled by obese dams (n=6), offspring of lean suckled by obese dams (n=5) and offspring of obese suckled by lean dams (n=6). All offspring were weaned onto a standard chow diet at 21 days and sacrificed at 3 months post-partum for tissue collection.
Offspring subjected to an adverse suckling environment showed significant increases in body weight, pancreatic triglyceride content, TGF-beta, collagen gene expression and SBP at rest along with an enhanced restraint stress response, indicating a dysmetabolic and NAFPD phenotype.
Developmental programming is involved in the pathogenesis of NAFPD and appears to be largely dependent on an adverse extra-uterine environment.
胰腺腺癌（PAC）的患病率与肥胖和代谢紊乱的发生率呈正相关，这可能与非酒精性脂肪性胰腺疾病（NAFPD）有关。我们最近发现，母体肥胖会使成年后代的代谢紊乱和脂肪肝（非酒精性脂肪肝疾病，NAFLD）表型发育。由于胰腺和肝脏起源于同一个胚胎芽，母体肥胖可能同样会使 NAFPD 发育的可能性是合理的。我们的目的是确定母体肥胖对后代 NAFPD 发育的影响，并确定宫内/宫外时期的贡献。
雌性 C57BL/6J 小鼠在交配前六周和整个怀孕及哺乳期内分别喂食标准饲料（3%脂肪，7%糖）或高热量饲料（16%脂肪，33%糖）。雌性后代被交叉寄养给同一或相反饮食的母鼠，以产生四个组：瘦母鼠哺乳的瘦后代（n=6）、肥胖母鼠哺乳的肥胖后代（n=6）、瘦母鼠哺乳的肥胖后代（n=5）和肥胖母鼠哺乳的瘦后代（n=6）。所有后代在 21 天断奶并喂食标准饲料，并在产后 3 个月时处死以收集组织。
暴露于不良哺乳环境的后代体重、胰腺甘油三酯含量、TGF-β、胶原基因表达和静息状态下的 SBP 显著增加，同时应激反应增强，表明代谢紊乱和 NAFPD 表型。
发育编程参与了 NAFPD 的发病机制，并且似乎主要依赖于不良的宫外环境。
