中文摘要 研究背景 肥胖在全世界的盛行率有逐年上升的趨勢，與肥胖相關的疾病也隨之增加。先前研究指出體能活動可以明顯減低高脂肪飲食所引起的肥胖。此外，也有文獻指出給予熱量限制的飲食可以有效地防止高脂肪飲食所引起的代謝異常。單碳代謝參與人體許多重要的生理調控路徑，並且影響生物體內的甲基化變化，而單碳代謝的失調在人體疾病過程也扮演重要角色。本研究的目的為探討給予不同的飲食介入與體能活動對於單碳代謝的影響。 實驗設計 給予小鼠不同飲食介入及體能活動，分析其單碳代謝路徑中相關代謝產物、酵素活性、基因表現並以穩定同位素追蹤單碳路徑動態平衡變化。 結果 在動物模式中，高脂肪飲食介入會導致小鼠的肥胖，並且影響單碳代謝相關酵素的活性；而給予不同飲食介入及體能活動後，也會部分影響單碳代謝途徑的變化。 結論 高脂肪飲食誘發肥胖所造成的體內單碳代謝改變，可以部分的被不同飲食介入或體能活動扭轉回復。 Abstract Background. The epidemic occurrence of obesity in the general population has caused an increase in the incidence of obesity-associated diseases. Endurance exercise significantly attenuated high-fat diet-induced obesity. Caloric restriction dramatically prevented high-fat diet-induced metabolic abnormalities. The objective of this study was to investigate the effects of long-term high fat consumption, physical activity and caloric restriction on one-carbon metabolism. Design and Methods. Forty-two male C57BL/6JNarl mice aged 5-week-old, were randomly assigned to three treatment groups: control diet group, caloric restriction diet group and high-fat diet group. After 12 weeks of dietary intervention, CTL group were further subdivided into control and control diet with exercise; high-fat diet-fed mice were further subdivided into high-fat diet, high-fat diet with exercise, control diet with 30% caloric restriction, and control diet with 30% caloric restriction combined exercise groups. Metabolic kinetic studies were conducted after the 15-week intervention period by stable isotopic tracers and GC/MS. Results and conclusions. Long-term high-fat consumption, caloric restriction, or physical activity significantly altered body weight and body fat. They also significantly altered hepatic adenosylmethionine formation and utilization. Long-term high-fat consumption and caloric restriction significantly altered hepatic transmethylation gene expression profile whereas global genomic DNA methylation remained unchanged in the liver. Some of the alterations induced by high fat consumption were reversed by caloric restriction and/or physical activity. Further studies are needed to determine the underlying mechanism(s) by which maternal high-fat exposure during may result in alterations in 1-carbon metabolism.