Lifelong Caloric Restriction Reprograms Hepatic Fat Metabolism in Mice
Lifelong Caloric Restriction Reprograms Hepatic Fat Metabolism in Mice
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DOI：
10.1093/gerona/glt160
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发表时间：
2014-08-01
影响因子：
5.1
通讯作者：
Vollmar, Brigitte
中科院分区：
文献类型：
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作者：
Kuhla, Angela;Hahn, Steffi;Vollmar, Brigitte
通过迄今未知的机制，降低卡路里可以减缓衰老过程，延长不同物种的寿命。卡路里摄入量与寿命之间的反线性关系表明，能量代谢调节器在衰老过程中起着重要作用。目前的研究表明，终生热量限制诱导了代谢适应，减少了脂肪生成，增强了脂肪分解和酮类生成。这一过程，即肝脏脂肪代谢的重新编程，与成纤维细胞生长因子21作为假定的饥饿主要调节因子的显著上升有关。由于成纤维细胞生长因子21具有延长寿命的特性，成纤维细胞生长因子21的升高可能有助于终生限制热量喂养的小鼠显著改善健康状况。此外，阿德罗平，作为一种控制脂质稳态的多肽，显著上调，强调了脂肪生成的减少，进一步证实了肝脏X受体α及其靶基因类固醇调节元件结合蛋白-1c、脂肪酸合成酶和人类转运蛋白亚家族ABCA成员1的表达减少。
Calorie lowering slows the aging process and extends life span in diverse species by so far unknown mechanisms. The inverse linear relationship between calorie intake and life span suggests that regulators of energy metabolism are of importance in aging. The present study shows that lifelong caloric restriction in mice induces a metabolic adaptation with reduced lipogenesis and enhanced lipolysis and ketogenesis. This process, that is, the reprogramming of hepatic fat metabolism, is associated with a marked rise of fibroblastic growth factor 21 as a putative starvation master regulator. Due to the life span-extending properties of fibroblastic growth factor 21, the rise in fibroblastic growth factor 21 might contribute to the markedly better health status found in mice upon lifelong caloric restriction feeding. In addition, adropin, known as a peptide that controls lipid homeostasis, is significantly upregulated, underlining the diminution of lipogenesis that was further substantiated by decreased expression of liver-X-receptor alpha and its target genes sterol regulatory element-binding protein-1c, fatty acid synthase, and member 1 of human transporter subfamily ABCA upon lifelong caloric restriction feeding.