PMID- 20716918 OWN - NLM STAT- MEDLINE DCOM- 20110112 LR - 20211020 IS - 1942-0994 (Electronic) IS - 1942-0900 (Print) IS - 1942-0994 (Linking) VI - 2 IP - 5 DP - 2009 Nov-Dec TI - The fat-1 transgene in mice increases antioxidant potential, reduces pro-inflammatory cytokine levels, and enhances PPAR-gamma and SIRT-1 expression on a calorie restricted diet. PG - 307-16 LID - 10.4161/oxim.2.5.9579 [doi] AB - Both n-3 fatty acids (FA) and calorie-restriction (CR) are known to exert anti-inflammatory and anti-oxidative effects in animals and humans. In this study, we investigated the synergistic anti-inflammatory and anti-oxidative capacity of n-3 FA and CR using Fat-1 transgenic mice (Fat-1) that are capable of converting n-6 FA to n-3 FA endogenously. Wild type (WT) and Fat-1 mice were maintained on ad libitum (AL) or CR (40% less than AL) AIN-93 diet supplemented with 10% corn oil (rich in n-6 FA) for 5 months. Significantly lower levels of n-6/n-3 FA ratio were observed in serum, muscle and liver of Fat-1 mice fed AL or CR as compared to that of WT mice fed AL or CR. Muscle catalase (CAT), super oxide dismutase (SOD), glutathione peroxidase (GPX) activities, and liver CAT and SOD activities were found higher in Fat-1 mice as compared to that of WT mice. These activities were more pronounced in Fat-1/CR group as compared to other groups. Serum pro-inflammatory markers, such as tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, and IL-6 were found lower in Fat-1 mice, as compared to that of WT mice. This anti-inflammatory effect was also more pronounced in Fat-1/CR group as compared to that of other groups. Furthermore, significantly higher levels of peroxisome proliferator-activated receptor (PPAR)-gamma and life prolonging gene, sirtuin (SIRT)-1 expression were found in liver of Fat-1/CR mice, as compared to that of WT/CR mice. These data suggest that n-3 FA along with moderate CR may prolong lifespan by attenuating inflammation and oxidative stress. FAU - Rahman, Mizanur AU - Rahman M AD - Department of Medicine, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA. rahmanm@uthscsa.edu FAU - Halade, Ganesh V AU - Halade GV FAU - Bhattacharya, Arunabh AU - Bhattacharya A FAU - Fernandes, Gabriel AU - Fernandes G LA - eng GR - R01 AG030161/AG/NIA NIH HHS/United States GR - R01 AT004259/AT/NCCIH NIH HHS/United States GR - AT005232-01/AT/NCCIH NIH HHS/United States GR - -AG030161/AG/NIA NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PL - United States TA - Oxid Med Cell Longev JT - Oxidative medicine and cellular longevity JID - 101479826 RN - 0 (Antioxidants) RN - 0 (Cadherins) RN - 0 (Cytokines) RN - 0 (Fatty Acids, Omega-3) RN - 0 (Interleukin-1beta) RN - 0 (Interleukin-6) RN - 0 (PPAR gamma) RN - 0 (Tumor Necrosis Factor-alpha) RN - 0 (fat1 protein, mouse) RN - EC 1.11.1.6 (Catalase) RN - EC 1.11.1.9 (Glutathione Peroxidase) RN - EC 1.15.1.1 (Superoxide Dismutase) RN - EC 3.5.1.- (Sirtuin 1) SB - IM MH - Animals MH - Antioxidants/*metabolism MH - Cadherins/*genetics/metabolism MH - *Caloric Restriction MH - Catalase/metabolism MH - Cytokines/*metabolism MH - Fatty Acids, Omega-3/pharmacology MH - Glutathione Peroxidase/metabolism MH - Interleukin-1beta/blood/metabolism MH - Interleukin-6/blood/metabolism MH - Liver/metabolism MH - Male MH - Mice MH - Mice, Inbred C57BL MH - Mice, Transgenic MH - PPAR gamma/*metabolism MH - Sirtuin 1/*metabolism MH - Superoxide Dismutase/metabolism MH - Tumor Necrosis Factor-alpha/blood/metabolism PMC - PMC2835919 EDAT- 2010/08/19 06:00 MHDA- 2011/01/13 06:00 CRDT- 2010/08/19 06:00 PHST- 2010/08/19 06:00 [entrez] PHST- 2010/08/19 06:00 [pubmed] PHST- 2011/01/13 06:00 [medline] AID - 9579 [pii] AID - 1942-0900-2-5-7 [pii] AID - 10.4161/oxim.2.5.9579 [doi] PST - ppublish SO - Oxid Med Cell Longev. 2009 Nov-Dec;2(5):307-16. doi: 10.4161/oxim.2.5.9579.