title: Omega-3 fatty acids partially revert the metabolic gene expression profile induced by long-term calorie restriction.
abstract: Calorie restriction (CR) consistently extends longevity and delays age-related diseases across several animal models. We have previously shown that different dietary fat sources can modulate life span and mitochondrial ultrastructure, function and membrane fatty acid composition in mice maintained on a 40% CR. In particular, animals consuming lard as the main fat source (CR-Lard) lived longer than CR mice consuming diets with soybean oil (CR-Soy) or fish oil (CR-Fish) as the predominant lipid source. In the present work, a transcriptomic analysis in the liver and skeletal muscle was performed in order to elucidate possible mechanisms underlying the changes in energy metabolism and longevity induced by dietary fat in CR mice. After 8 months of CR, transcription downstream of several mediators of inflammation was inhibited in liver. In contrast, proinflammatory signaling was increased in the CR-Fish versus other CR groups. Dietary fish oil induced a gene expression pattern consistent with increased transcriptional regulation by several cytokines (TNF, GM-CSF, TGF-β) and sex hormones when compared to the other CR groups. The CR-Fish also had lower expression of genes involved in fatty acid biosynthesis and increased expression of mitochondrial and peroxisomal fatty acid β-oxidation genes than the other CR diet groups. Our data suggest that a diet high in n-3 PUFA, partially reverts CR-related changes in gene expression of key processes, such as inflammation and steroid hormone signaling, and this may mitigate life span extension with CR in mice consuming diets high in fish oil.
authors.affiliation: Department of Molecular Biosciences, School of Veterinary Medicine, University of California, Davis, USA. Electronic address: jlopez-dominguez@buckinstitute.org.
authors.forename: José Alberto
authors.initials: JA
authors.lastname: López-Domínguez
authors.affiliation: Department of Animal Science, University of California, Davis, USA.
authors.forename: Ángela
authors.initials: Á
authors.lastname: Cánovas
authors.affiliation: Department of Animal Science, University of California, Davis, USA.
authors.forename: Juan F
authors.initials: JF
authors.lastname: Medrano
authors.affiliation: Department of Animal Science, University of California, Davis, USA.
authors.forename: Alma
authors.initials: A
authors.lastname: Islas-Trejo
authors.affiliation: Department of Public Health, School of Medicine, University of California, Davis, USA.
authors.forename: Kyoungmi
authors.initials: K
authors.lastname: Kim
authors.affiliation: Department of Public Health, School of Medicine, University of California, Davis, USA.
authors.forename: Sandra L
authors.initials: SL
authors.lastname: Taylor
authors.affiliation: Departamento de Biología Celular, Fisiología e Inmunología, Universidad de Córdoba, Campus de Excelencia Internacional Agroalimentario, ceiA3, Spain.
authors.forename: José Manuel
authors.initials: JM
authors.lastname: Villalba
authors.affiliation: Centro Andaluz de Biología del Desarrollo (CABD), Universidad Pablo de Olavide-CSIC, CIBERER, Instituto de Salud Carlos III, Sevilla, Spain.
authors.forename: Guillermo
authors.initials: G
authors.lastname: López-Lluch
authors.affiliation: Centro Andaluz de Biología del Desarrollo (CABD), Universidad Pablo de Olavide-CSIC, CIBERER, Instituto de Salud Carlos III, Sevilla, Spain.
authors.forename: Plácido
authors.initials: P
authors.lastname: Navas
authors.affiliation: Department of Molecular Biosciences, School of Veterinary Medicine, University of California, Davis, USA.
authors.forename: Jon J
authors.initials: JJ
authors.lastname: Ramsey
mesh_terms: D000818:Animals; D001835:Body Weight; D031204:Caloric Restriction; D004734:Energy Metabolism / Q000187:drug effects*; D015525:Fatty Acids, Omega-3 / Q000494:pharmacology*; D020869:Gene Expression Profiling; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism; D009929:Organ Size; D011897:Random Allocation
chemical_list: D015525:Fatty Acids, Omega-3
keywords: Calorie restriction; Dietary fat; Gene expression; Omega-3 fatty acids