Department of Veterinary Basic Sciences, The Royal Veterinary College, Royal College Street, London NW1 0TU, United Kingdom.
Endocrinology. 2010 Apr;151(4):1451-61. doi: 10.1210/en.2009-1192. Epub 2010 Mar 5.
With rising obesity rates, nonalcoholic fatty liver disease is predicted to become the main cause of chronic liver disease in the next decades. Rising obesity prevalence is attributed to changes in dietary habits with increased consumption of palatable junk foods, but maternal malnutrition also contributes to obesity in progeny. This study examines whether a maternal junk food diet predisposes offspring to nonalcoholic fatty liver disease. The 144 rat offspring were fed either a balanced chow diet alone or with palatable junk foods rich in energy, fat, sugar, and/or salt during gestation, lactation, and/or after weaning up to the end of adolescence. Offspring fed junk food throughout the study exhibited exacerbated hepatic steatosis, hepatocyte ballooning, and oxidative stress response compared with offspring given free access to junk food after weaning only. These offspring also displayed sex differences in their hepatic molecular metabolic adaptation to diet-induced obesity with increased expression of genes associated with insulin sensitivity, de novo lipogenesis, lipid oxidation, and antiinflammatory properties in males, whereas the gene expression profile in females was indicative of hepatic insulin resistance. Hepatic inflammation and fibrosis were not detected indicating that offspring had not developed severe steatohepatitis by the end of adolescence. Hepatic steatosis and increased oxidative stress response also occurred in offspring born to junk food-fed mothers switched to a balanced chow diet from weaning, highlighting a degree of irreversibility. This study shows that a maternal junk food diet in pregnancy and lactation contributes to the development of nonalcoholic fatty liver disease in offspring.
随着肥胖率的上升，非酒精性脂肪性肝病预计将在未来几十年成为慢性肝病的主要原因。肥胖患病率的上升归因于饮食习惯的改变，人们增加了对美味垃圾食品的消费，但母体营养不良也导致了后代肥胖。本研究探讨了母体垃圾食品饮食是否使后代易患非酒精性脂肪性肝病。144 只大鼠后代在妊娠期、哺乳期和/或断奶后至青春期结束期间，分别单独或同时喂食均衡的饲料或富含能量、脂肪、糖和/或盐的美味垃圾食品。与仅在断奶后自由食用垃圾食品的后代相比，整个研究期间食用垃圾食品的后代表现出更严重的肝脂肪变性、肝细胞气球样变和氧化应激反应。这些后代在其肝脏对饮食诱导肥胖的分子代谢适应方面也表现出性别差异，与胰岛素敏感性、从头脂肪生成、脂质氧化和抗炎特性相关的基因表达增加，而女性的基因表达谱表明存在肝胰岛素抵抗。未检测到肝炎症和纤维化，表明在青春期结束时，后代尚未发展为严重的脂肪性肝炎。从断奶开始，喂食垃圾食品的母亲转为均衡饮食的后代也出现了肝脂肪变性和氧化应激反应增加，这突出了一定程度的不可逆转性。本研究表明，母体在妊娠和哺乳期的垃圾食品饮食会导致后代发生非酒精性脂肪性肝病。
