Biochemical and Biophysical Research Communications
Inhibition of inflammatory response in transgenic fat-1 mice on a calorie-restricted diet
Section snippets
Materials and methods
Animals and experimental diets. Heterozygous fat-1 mice on C57BL/6 background [24] were previously described. These animals show no phenotypic changes. Fat-1 heterozygous and the non-transgenic litter mate controls were used in the study. Presence of fat-1 gene was confirmed by genotyping and fatty acid composition of tails by gas chromatography (GC). Age- and weight-matched mice were housed in a laboratory animal care facility in cages (3–4 mice/cage) and fed semi-purified AIN-93 M diets
Body weight
Body weights increased gradually in WT/AL and fat-1/AL mice but there was no difference between the 2 groups (p = 0.38). As expected, CR reduced body weight in both WT and fat-1 mice as compared to AL mice, but the difference were not statistically different between the 2 groups (p = 0.18) (Fig. 1).
Fatty acid composition of splenocytes
We performed GC to determine the effect of fat-1 transgene on fatty acid composition of splenocytes. Our results showed decrease in n − 6/n − 3 FA ratio in fat-1/AL and fat-1/CR mice as compared to WT/AL
Discussion
This is the first study to demonstrate the inhibition of LPS-induced inflammatory response in fat-1 transgenic mice on CR diet. There was significant inhibition of NF-κB p65/p50 activity, AP-1 c-Fos/c-Jun activity, and pro-inflammatory cytokine expression, ex vivo, in fat-1/CR mice. These findings suggest that n − 3 FA and CR, in combination, may prevent or delay the progression of inflammatory diseases. We previously demonstrated the anti-inflammatory and life-prolonging effects of n − 3 FA in
Acknowledgments
We thank Kazi Nishu for her assistance in diet preparation and animal maintenance. This work was supported by the National Institutes of Health Grants AG023648 and AG027562 (G.F.), by the Research Service of the Department of Veterans Affairs (B.C.), and the American Cancer Society Grant RSG-03-140-01-CNE (J.X.K).
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