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Aerobic Exercise Improves Obesity-Induced Lymphatic Dysfunction Independent of Weight Loss
Geoffrey E. Hespe, BS, Raghu P. Kataru, PhD, Ira L. Savetsky, MD, Gabriela D. García Nores, MD, Jeremy S. Torrisi, BA, Matthew D. Nitti, BA, Jason C. Gardenier, MD, Jie Zhou, MD, Jessie Z. Yu, MD, Jung-Ju Huang, MD, Lee W. Jones, PhD, Babak J. Mehrara, MD.
Memorial Sloan Kettering Cancer Center, New York, NY, USA.

PURPOSE:
Obesity has been shown to decrease lymphatic function and, in turn, amplify the pathologic responses in obesity. However, the cellular mechanisms that regulate this response remain unknown. The purpose of this study was to analyze lymphatic vascular changes in obese mice and determine if these pathologic effects are reversible with aerobic exercise.
METHODS:
Male C57/BL6J mice were fed a high-fat diet (HFD) for 10-12 weeks to induce obesity and then were randomized to an aerobic exercise group (treadmill running for 6 weeks) or a sedentary group that was not exercised. Lean control mice remained sedentary and fed a normal chow diet. At the conclusion of the experiment, we analyzed lymphatic function, histological changes, and lymphatic endothelial cell (LEC) gene expression.
RESULTS:
Sedentary obese mice had markedly decreased collecting lymphatic vessel pumping capacity, decreased lymphatic vessel density, decreased lymphatic migration of immune cells, and increased lymphatic vessel leakiness as compared with lean animals. Aerobic exercise, independent of weight loss, markedly improved lymphatic function and significantly decreased perilymphatic accumulation of inflammatory cells and iNOS expression, as compared with sedentary obese mice. In addition, exercise normalized isolated LEC gene expression of lymphatic specific genes (VEGFR-3 and Prox1).
CONCLUSION:
This study, for the first time, suggests that implementation of aerobic exercise in the setting of obesity can improve lymphatic function and may limit some of the pathologic consequences of obesity, independent of weight loss. These findings provide a mechanism for recommending aerobic exercise to patients who are at risk for developing lymphedema.


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