Abnormal Immune Responses in fa/fa Zucker Rats and Effects of Feeding Conjugated Linoleic Acid




Objective: The objective of this study was to characterize immune function in the fa/fa Zucker rat, and to determine the effects of feeding conjugated linoleic acid (CLA) isomers on immune function.

Methods and Procedures: Lean and fa/fa Zucker rats were fed for 8 weeks nutritionally complete diets with different CLA isomers (%wt/wt): control (0%), c9t11 (0.4%), t10c12 (0.4%), or MIX (0.4% c9t11 + 0.4% t10c12). Isolated splenocytes were used to determine phospholipid (PL) fatty acid composition and cell phenotypes, or stimulated with mitogen to determine their ability to produce cytokines, immunoglobulins (Ig), and nitric oxide (NO).

Results: Splenocyte PL of fa/fa rats had a higher proportion of total monounsaturated fatty acids and n −3 polyunsaturated fatty acids (PUFA), and lower n −6 PUFA and n −6-to-n −3 PUFA ratio (P < 0.05). Feeding CLA increased the content of CLA isomers into PL, but there were lower proportions of each CLA isomer in fa/fa rats. Splenocytes of fa/fa rats produced more amounts of IgA, IgG, and IgM, NO, and interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-α (TNF-α) (P < 0.05). Obese rats fed the t10c12 diet produced less TNF-α and IL-1β (lippopolysaccharide (LPS), P < 0.05). Splenocytes of fa/fa rats produced less concanavalin A (ConA)-stimulated IL-2 (P < 0.0001) than lean rats, except fa/fa rats fed the c9t11 diet (P < 0.05).

Discussion: The c9t11 and t10c12 CLA isomers were incorporated into the membrane PL of the fa/fa Zucker rat, but to a lesser extent than lean rats. Splenocytes of obese rats responded in a proinflammatory manner and had reduced T-cell function and feeding the t10c12 and c9t11 CLA isomers may improve some of these abnormalities by distinct methods.