title: Lifelong caloric restriction reprograms hepatic fat metabolism in mice.
abstract: 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.
authors.affiliation: Institute for Experimental Surgery and angela.kuhla@uni-rostock.de.
authors.forename: Angela
authors.initials: A
authors.lastname: Kuhla
authors.affiliation: Institute for Experimental Surgery and.
authors.forename: Steffi
authors.initials: S
authors.lastname: Hahn
authors.affiliation: Institute for Experimental Surgery and.
authors.forename: Antje
authors.initials: A
authors.lastname: Butschkau
authors.affiliation: Institute of Anatomy, University of Rostock, Germany.
authors.forename: Sophie
authors.initials: S
authors.lastname: Lange
authors.affiliation: Institute of Anatomy, University of Rostock, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Wree
authors.affiliation: Institute for Experimental Surgery and.
authors.forename: Brigitte
authors.initials: B
authors.lastname: Vollmar
mesh_terms: D000222:Adaptation, Physiological / Q000502:physiology; D000818:Animals; D015153:Blotting, Western; D001835:Body Weight / Q000502:physiology; D031204:Caloric Restriction; D004734:Energy Metabolism / Q000502:physiology*; D005260:Female; D005346:Fibroblast Growth Factors / Q000378:metabolism; D007150:Immunohistochemistry; D036341:Intercellular Signaling Peptides and Proteins; D050152:Intra-Abdominal Fat / Q000502:physiology; D050155:Lipogenesis / Q000502:physiology*; D008099:Liver / Q000737:chemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D011506:Proteins / Q000378:metabolism*; D015854:Up-Regulation / Q000502:physiology
chemical_list: C534289:Enho protein, mouse; D036341:Intercellular Signaling Peptides and Proteins; D011506:Proteins; C414620:fibroblast growth factor 21; D005346:Fibroblast Growth Factors
keywords: Adropin; FGF21; Ketogenesis.; Leptin; Lipolysis