不同生命期之飲食介入對於單碳代謝之影響

Abstract

背景 許多疾病可能造成體內單碳代謝失衡。肥胖是21世紀一個重要的全球衛生問題，近年來世界各地兒童肥胖盛行率有顯著增加。過去研究顯示孕婦肥胖或在懷孕和哺乳期間攝取高脂肪的飲食會增加子代肥胖及相關代謝疾病的風險。本研究探討母鼠懷孕和哺乳期間的營養狀況及產後的飲食對於其子代體內單碳代謝之影響。實驗設計 C57BL / 6實驗小鼠分為下列幾組：(1) 正常飲食組: 母代及子代均給予正常飲食; (2) 斷奶後高脂飲食組:母代整個生命期均給予正常飲食而其子代於斷奶後給予高脂飲食; (3) 哺乳期高脂飲食組：母代哺乳期間給予高脂飲食而其子代於斷奶後亦給予高脂飲食; (4) 哺乳期高脂飲食切換組:母代哺乳期給予高脂飲食而子代於斷奶後給予正常飲食; (5) 交配期高脂飲食組:母代交配及懷孕哺乳期間給予高脂飲食而子代於斷奶後給予高脂飲食; (6)交配期高脂飲食切換組：母代交配及懷孕哺乳期間給予高脂飲食而子代於斷奶後給予正常飲食。於子代斷奶介入四週後以穩定同位素追蹤單碳路徑動態平衡變化。實驗當中記錄子代體重及食物攝取量。子代於實驗結束後犧牲，測量體內脂肪含量以及其單碳代謝路徑中相關代謝產物、酵素活性、基因表現變化。 結果及結論 母代高脂飲食攝取會增加子代體重和白色脂肪含量。母代於不同時期攝取高脂肪飲食後，依其不同生命期間高脂飲食的介入及暴露程度，對於小鼠肥胖及體脂變化有不同程度之影響，同時亦顯著影響其子代單碳代謝相關酵素活性、代謝產物、基因表現及單碳代謝之動態平衡。

Background. The prevalence of childhood obesity has increased dramatically around the world in recent years, and obesity is considered a major global health issue in the 21th century. Maternal nutritional status and postnatal diet may influence the lifelong health of offspring. Maternal obesity and consumption of a high-fat diet during pregnancy and lactation have been found to increase the risk for development of obesity and related metabolic disorders in the offspring. One carbon metabolism is involved in multiple biological processes, and perturbation in the one carbon metabolic pathways has been associated with numerous pathological conditions. The objective of the current study was to investigate how maternal high fat exposure may alter 1-carbon metabolism in the offspring. Design and Methods. C57BL/6 mice were assigned into 6 groups: (1) control group: parental mice received the control diet throughout their life including pregnancy and lactation; offspring mice also received the control diet postweaning; (2) weaning high fat group: parental mice received the control diet throughout their life including pregnancy and lactation; offspring mice received the high fat diet postweaning; (3) lactation high fat group: maternal mice received the control diet during pregnancy and then switched to the high fat diet during lactation; offspring mice received the high fat diet postweaning; (4) lactation high fat switch-back group: maternal mice received the control diet during pregnancy and switched to the high fat diet during lactation; offspring mice received the control diet post weaning; (5) mating high fat group: maternal mice received the high fat diet during pregnancy and lactation; offspring mice received the high fat diet postweaning; (6) mating high fat switch-back group: maternal mice received the high fat diet during pregnancy and lactation; offspring mice received the control diet postweaning. The body weight and food intake were monitored throughout the study period. The animals were sacrificed 4 weeks postweaning. Major metabolites and the activity and expression of key enzymes in 1-carbon metabolism were determined. Metabolic fluxes in1-carbon metabolism was determined using stable isotopic tracers and GC/MS. Maternal high fat consumption at different life stages significantly altered body weight and body fat distribution in their offspring mice. It also significantly altered hepatic adenosylmethionine formation and utilization in the liver. Further studies are needed to determine the underlying mechanism(s) by which maternal high-fat consumption may result in alterations in 1-carbon metabolism in the offspring.