Lifelong caloric restriction reprograms hepatic fat metabolism in mice.
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 α 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.
['Kuhla|Angela|A|', 'Hahn|Steffi|S|', 'Butschkau|Antje|A|', 'Lange|Sophie|S|', 'Wree|Andreas|A|', 'Vollmar|Brigitte|B|']
D000222:Adaptation, Physiological D000818:Animals D015153:Blotting, Western D001835:Body Weight D031204:Caloric Restriction D004734:Energy Metabolism D005260:Female D005346:Fibroblast Growth Factors D007150:Immunohistochemistry D036341:Intercellular Signaling Peptides and Proteins D050152:Intra-Abdominal Fat D050155:Lipogenesis D008099:Liver D051379:Mice D008810:Mice, Inbred C57BL D011506:Proteins D015854:Up-Regulation
Lipolysis Ketogenesis. Adropin FGF21 Leptin