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Publication : Inhibition of inflammatory response in transgenic fat-1 mice on a calorie-restricted diet.

First Author  Bhattacharya A Year  2006
Journal  Biochem Biophys Res Commun Volume  349
Issue  3 Pages  925-30
PubMed ID  16962071 Mgi Jnum  J:113093
Mgi Id  MGI:3664494 Doi  10.1016/j.bbrc.2006.08.093
Citation  Bhattacharya A, et al. (2006) Inhibition of inflammatory response in transgenic fat-1 mice on a calorie-restricted diet. Biochem Biophys Res Commun 349(3):925-30
abstractText  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.
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