Inhibition of inflammatory response in transgenic fat-1 mice on a calorie-restricted diet.
Both n-3 fatty acids (n-3 FA) and calorie-restriction (CR) exert anti-inflammatory effects in animal models of autoimmunity and inflammation. In the present study we investigated the synergistic anti-inflammatory effects of n-3 FA and CR on LPS-mediated inflammatory responses using fat-1 transgenic mice that generate n-3 FA endogenously. Wild-type (WT) and fat-1 mice were maintained on ad libitum (AL) or CR (40% less than AL) diet for 5 mo; splenocytes were cultured in vitro with/without LPS. Our results show: (i) no difference in body weights between WT and fat-1 mice on AL or CR diets, (ii) lower n-6/n-3 FA ratio in splenocytes from fat-1 mice on both AL and CR diets, (iii) significant reduction in NF-kappaB (p65/p50) and AP-1 (c-Fos/c-Jun) DNA-binding activities in splenocytes from fat-1/CR mice following LPS treatment, and (iv) significant reduction in kappaB- and AP-1-responsive IL-6 and TNF-alpha secretion following LPS treatment in splenocytes from fat-1/CR mice. The inhibition of LPS-mediated effects was more pronounced in fat-1/CR mice when compared to fat-1/AL or WT/CR mice. These data show that transgenic expression of fat-1 results in decreased pro-inflammatory n-6 FA, and demonstrate for the first time that splenocytes from fat-1 mice on CR diet exhibit reduced pro-inflammatory response when challenged with LPS. These results suggest that n-3 lipids with moderate CR may confer protection in autoimmune and inflammatory diseases.
Bhattacharya
Arunabh
A
Department of Medicine, Division of Clinical Immunology and Rheumatology, University of Texas Health Science Center, San Antonio, TX 78229, USA.
Chandrasekar
Bysani
B
Rahman
Md Mizanur
MM
Banu
Jameela
J
Kang
Jing X
JX
Fernandes
Gabriel
G
D000818:Animals; D001835:Body Weight; D031204:Caloric Restriction; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism; D007249:Inflammation / Q000139:chemically induced / Q000178:diet therapy / Q000235:genetics / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D016328:NF-kappa B / Q000378:metabolism; D010641:Phenotype; D013154:Spleen / Q000187:drug effects / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000378:metabolism
D016207:Cytokines; D005227:Fatty Acids; D008070:Lipopolysaccharides; D016328:NF-kappa B; D018808:Transcription Factor AP-1