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

Arunabh Bhattacharya, Bysani Chandrasekar, Md Mizanur Rahman, Jameela Banu, Jing X. Kang, Gabriel Fernandes

Research output: Contribution to journalArticlepeer-review

39 Scopus citations

Abstract

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-κB (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 κB- and AP-1-responsive IL-6 and TNF-α 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.

Original languageEnglish (US)
Pages (from-to)925-930
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume349
Issue number3
DOIs
StatePublished - Oct 27 2006

Keywords

  • AP-1
  • Calorie-restriction
  • Cytokines
  • Fat-1
  • Inflammation
  • NF-κB
  • Splenocytes
  • n - 3 fatty acids

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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