Obesity increases inflammation and impairs lymphatic function in a mouse model of lymphedema

淋巴系统 炎症 医学 纤维化 淋巴水肿 脂肪组织 淋巴管新生 内科学 内分泌学 病理 癌症 转移 乳腺癌
作者
Ira L. Savetsky,Jeremy S. Torrisi,Daniel A. Cuzzone,Swapna Ghanta,Nicholas J. Albano,Jason C. Gardenier,Walter J. Joseph,Babak J. Mehrara
出处
期刊:American Journal of Physiology-heart and Circulatory Physiology [American Physiological Society]
卷期号:307 (2): H165-H172 被引量:116
标识
DOI:10.1152/ajpheart.00244.2014
摘要

Although obesity is a major clinical risk factor for lymphedema, the mechanisms that regulate this effect remain unknown. Recent reports have demonstrated that obesity is associated with acquired lymphatic dysfunction. The purpose of this study was to determine how obesity-induced lymphatic dysfunction modulates the pathological effects of lymphatic injury in a mouse model. We used a diet-induced model of obesity in adult male C57BL/6J mice in which experimental animals were fed a high-fat diet and control animals were fed a normal chow diet for 8–10 wk. We then surgically ablated the superficial and deep lymphatics of the midportion of the tail. Six weeks postoperatively, we analyzed changes in lymphatic function, adipose deposition, inflammation, and fibrosis. We also compared responses to acute inflammatory stimuli in obese and lean mice. Compared with lean control mice, obese mice had baseline decreased lymphatic function. Lymphedema in obese mice further impaired lymphatic function and resulted in increased subcutaneous adipose deposition, increased CD45 + and CD4 + cell inflammation ( P < 0.01), and increased fibrosis, but caused no change in the number of lymphatic vessels. Interestingly, obese mice had a significantly increased acute inflammatory reaction to croton oil application. In conclusion, obese mice have impaired lymphatic function at baseline that is amplified by lymphatic injury. This effect is associated with increased chronic inflammation, fibrosis, and adipose deposition. These findings suggest that obese patients are at higher risk for lymphedema due to impaired baseline lymphatic clearance and an increased propensity for inflammation in response to injury.
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