The effects of polyunsaturated fatty acids on immune function in obese insulin resistant rodents.

摘要

Altered immune responses have been reported in obese individuals, although the exact impairments have not been established. Conjugated linoleic acid (CLA), a group of positional and geometric isomers of linoleic acid, has been reported to beneficially alter immune function in healthy and inflammatory states. Long chain (n-3) polyunsaturated fatty acids (PUFA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), have established anti-inflammatory and immunoregulatory properties in autoimmune inflammatory states. However, the effects of these PUFA on immunity in obesity are unknown. Therefore, the objective of this thesis was to determine the effects of obesity and dietary PUFA on immunity.;In a short-term study, there was no difference in T-cell stimulated IL-2 production and there was lower stimulated IL-1β and IFN-γ (inflammatory cytokine) production by obese JCR:LA-cp rats compared to lean rats (P<0.05). However, in a long-term intervention, production of IL-1β and the Th1 response (IL-2 and IFN-γ) were higher in obese rats compared to lean rats. Higher levels of protein kinase C-&thetas; (PKC-&thetas;) may partly explain the higher IL-2 concentrations in obese rats. Obese rats fed fish oil (FO) had more long chain (n-3) PUFA and lower (n-6):(n-3) PUFA ratio in splenocyte phospholipids and lipid rafts. In the short-term intervention, obese FO-fed rats produced less IL-1β and IFN-γ without affecting IL-2 production. Whereas, high FO fed rats in the long-term intervention produced more IL-2, but this was not attributable to PKC-&thetas;.;Overall, T-cell and inflammatory cytokine responses are impaired in rodent models of obesity. Careful consideration of the immune parameter of interest is required to determine which model is most suitable. Dietary EPA and DHA and CLA have beneficial effects on T-cell function and inflammatory cytokine production.;The fa/fa Zucker rat had lower Concanavalin A (ConA)-stimulated IL-2 production (impaired T-cell function) and greater mitogen-stimulated IL-1β, TNF-α and IL-6 (inflammatory) cytokine production compared to lean rats (P<0.05). Feeding the cis9,trans 11 or trans10,cis12 CLA isomer singly or in combination to fa/fa Zucker rats resulted in incorporation into splenocyte phospholipids, but to a lesser extent than lean rodents. Feeding cis9,trans11 CLA to fa/fa rats improved IL-2 and IL-10 production to levels similar to lean rats fed the same diet. Obese rats fed trans10, cis12 CLA had lower LPS-stimulated IL-1β and TNF-α.