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Effects of feeding fish oil on mesenteric lymph node cytokine responses in obese leptin receptor-deficient JCR:LA-cp rats

Abstract

Objective:

Aberrant immune responses have been identified in obesity; however, immune cells of lymph nodes residing in the inflammatory environment of visceral adipose tissue have been largely overlooked. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) can reduce inflammation and modify T-cell function and therefore may improve immune function in obesity. Thus, we determined the effects of feeding fish oil (FO) containing EPA and DHA on mesenteric lymph node (MLN) immune cell function.

Methods:

In this study, 14-week-old obese, leptin receptor-deficient JCR:LA-cp rats (cp/cp) (n=10 per group) were randomized to one of three nutritionally adequate diets for 3 weeks: control (ctl, 0% EPA+DHA), low FO (LFO, 0.8% w/w EPA+DHA) or high FO (HFO, 1.4% w/w EPA+DHA). Lean JCR:LA-cp (Cp/cp or Cp/Cp) rats (n=5) were fed ctl diet. MLN cell phospholipid (PL) fatty acid composition, phenotypes and cytokine production were measured.

Results:

Obese ctl rats produced more IL-1β, IL-4 and IL-10, despite a higher proportion of (n−3) polyunsaturated fatty acids (PUFAs) and a lower (n−6):(n−3) PUFA ratio in MLN PL compared with lean ctl rats (P<0.05). Concanavalin A-stimulated IL-2 production did not differ from lean rats even though obese ctl rats had a lower proportion of CD4+CD25+ cells (P<0.05). Feeding FO to obese rats increased the incorporation of (n−3) PUFA into MLN PL and normalized production of IL-1β (HFO only), IL-4 and IL-10 to the levels similar to lean ctl rats (P<0.05).

Conclusion:

We demonstrate for the first time that obese JCR:LA-cp rats have impaired responses of MLN immune cells to mitogen stimulation and altered PL fatty acid composition. Feeding FO lowered the ex vivo inflammatory response (HFO only) and production of Th2 cytokines, without changing IL-2 production from ConA-stimulated splenocytes, which may occur independent of leptin signalling.

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Acknowledgements

We thank Chris Gerdung, Tara Martin and Susan Goruk for their excellent technical assistance and Kristina McNaughton and Sharon Sokolik for their exceptional care of the animals and assistance with this study. Funding for this study was made possible in part by contributions from Dairy Farmers of Canada, the Natural Sciences and Engineering Research Council of Canada (NSERC), Alberta Livestock and Industry Development Fund (ALIDF) and the Alberta Diabetes Institute. MR Ruth held the Muttart/Collip Diabetes Studentship from the Muttart Diabetes and Research Training Centre, University of Alberta, Edmonton, Alberta, Canada.

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Correspondence to C J Field.

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Ruth, M., Proctor, S. & Field, C. Effects of feeding fish oil on mesenteric lymph node cytokine responses in obese leptin receptor-deficient JCR:LA-cp rats. Int J Obes 33, 96–103 (2009). https://doi.org/10.1038/ijo.2008.227

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