Cell Biology Laboratory, Biomedical Research Station, Orentreich Foundation for the Advancement of Science, Inc., Cold Spring-on-Hudson, NY 10516, USA.
Metabolism. 2010 Jul;59(7):1000-11. doi: 10.1016/j.metabol.2009.10.023. Epub 2010 Jan 4.
Methionine restriction increases life span in rats and mice and reduces age-related accretion of adipose tissue in Fischer 344 rats. Recent reports have shown that adipose tissue mitochondrial content and function are associated with adiposity; therefore, the expression of genes involved in mitochondrial biogenesis and oxidative capacity was examined in white adipose tissue, liver, and skeletal muscle from Fischer 344 rats fed control (0.86% methionine) or methionine-restricted (0.17% methionine) diets for 3 months. Methionine restriction induced transcriptional changes of peroxisome proliferator-activated receptors, peroxisome proliferator-activated receptor coactivators 1alpha and 1beta, and some of their known target genes in all of these tissues. In addition, tissue-specific responses were elicited at the protein level. In inguinal adipose tissue, methionine restriction increased protein levels of peroxisome proliferator-activated receptor and peroxisome proliferator-activated receptor coactivator target genes. It also induced mitochondrial DNA copy number, suggesting mitochondrial biogenesis and corresponding with the up-regulation of citrate synthase activity. In contrast, methionine restriction induced changes in mitochondrial glycerol-3-phosphate dehydrogenase activity and stearoyl-coenzyme A desaturase 1 protein levels only in liver and uncoupling protein 3 and cytochrome c oxidase subunit IV protein levels only in skeletal muscle. No increase in mitochondrial DNA copy number was observed in liver and skeletal muscle despite an increase in mitochondrial citrate synthase activity. The results indicate that adiposity resistance in methionine-restricted rats is associated with mitochondrial biogenesis in inguinal adipose tissue and increased mitochondrial aerobic capacity in liver and skeletal muscle.
限制蛋氨酸摄入可延长大鼠和小鼠的寿命，并减少 Fischer 344 大鼠的脂肪组织在衰老过程中的积累。最近的研究报告表明，脂肪组织中线粒体的含量和功能与肥胖有关；因此，我们研究了饲喂对照（0.86%蛋氨酸）或蛋氨酸限制（0.17%蛋氨酸）饮食 3 个月的 Fischer 344 大鼠的白色脂肪组织、肝脏和骨骼肌中与线粒体生物发生和氧化能力相关的基因的表达。蛋氨酸限制可诱导过氧化物酶体增殖物激活受体、过氧化物酶体增殖物激活受体共激活因子 1α 和 1β 及其已知靶基因在所有这些组织中的转录变化。此外，还在蛋白水平上引起了组织特异性反应。在腹股沟脂肪组织中，蛋氨酸限制增加了过氧化物酶体增殖物激活受体和过氧化物酶体增殖物激活受体共激活因子靶基因的蛋白水平。它还诱导了线粒体 DNA 拷贝数的增加，提示线粒体生物发生，并与柠檬酸合酶活性的上调相对应。相比之下，蛋氨酸限制仅在肝脏中诱导甘油-3-磷酸脱氢酶活性和硬脂酰辅酶 A 去饱和酶 1 蛋白水平的变化，仅在骨骼肌中诱导解偶联蛋白 3 和细胞色素 c 氧化酶亚基 IV 蛋白水平的变化。尽管肝脏和骨骼肌中的线粒体柠檬酸合酶活性增加，但线粒体 DNA 拷贝数没有增加。这些结果表明，蛋氨酸限制大鼠的肥胖抵抗与腹股沟脂肪组织中线粒体生物发生以及肝脏和骨骼肌中线粒体有氧能力的增加有关。
