n-3 lipids and moderate CR inhibit inflammatory response in mice

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Inhibition of inflammatory response in transgenic fat-1 mice on a

calorie-restricted diet.

* Bhattacharya A,

* Chandrasekar B,

* Rahman MM,

* Banu J,

* Kang JX,

* Fernandes G.

Department of Medicine, Division of Clinical Immunology and

Rheumatology, University of Texas Health Science Center, San ,

TX 78229, USA.

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.

PMID: 16962071