Exercise Improves Innate and Adaptive Immune Responses in Obese Mice

Abstract

Obesity increases the risk of several solid tumors. Obesity-induced impairments in immunity may contribute to this relationship. We have previously shown that numerous innate and adaptive immune responses, including NK cell cytotoxicity, antigen-specific CD4+ T cell proliferation, and CD8+ T cell cytotoxicity, are impaired in diet-induced obese (DIO) mice. PURPOSE: The current study was designed to determine if the obesity-induced decrements in immunity were reversible with weight loss achieved via the most common obesity interventions used in humans: exercise (EX), energy restriction (ER), or a combination of EX+ER. METHODS: Female C57BL/6 mice consumed a 60 kcal% fat diet, with 20 kcal% protein & carbohydrate, ad libitum for 15 weeks to induce obesity. After achieving a mean (± SD) body weight of 48.3 ± 1.9 grams, DIO mice were randomized to one of the following intervention groups (n=7-9/group): 1) DIO controls, which continued on 60 kcal% fat diet ad libitum; 2) DIO mice with access to running wheels (DIO+EX); 3) DIO mice placed on an energy-restricted diet consisting of a 30% reduction in kcal from fat (DIO+ER); or 4) DIO mice placed on an ER diet with access to running wheels (DIO+ER+EX). Mice were on one of the four interventions for 8 weeks prior to receiving a primary vaccination followed by 2 booster vaccinations 2 weeks apart. Animals were sacrificed 3 weeks following the last boost, and spleens were collected for assessment of immune function. RESULTS: Only mice on the ER diets (DIO+ER and DIO+ER+EX mice) weighed significantly less than the DIO control mice (P<0.05). Despite the lack of significant change in body weight with the exercise intervention alone, EX (either alone or in combination with ER) significantly (P <0.05) enhanced NK cell cytotoxicity, antigen-specific CD4+ T cell proliferation, and CD8+ T cell cytotoxicity in DIO mice, whereas ER alone did not. These findings demonstrate that obesity-induced immune impairments in NK cell and T cell function can be reversed by EX or a combination of ER plus EX, but not ER alone. CONCLUSION: These results suggest that in obese mice exercise enhances immune function independently of changes in body weight, and that in humans exercise may be an important intervention to couple with energy restriction to reduce body weight and enhance immune responsiveness in obese patients.