Inflammation Precedes Fat Deposition in an Experimental Model of Lymphedema

Autor(es)

Cuadrado, Guilherme A. ^[1] ; de Andrade, Mauro F. C. ^[2] ; Ariga, Suely K. ^[1] ; de Lima, Thais M. ^[1] ; Souza, Heraldo P. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Fac Med, Dept Emergency Med, Sao Paulo - Brazil

^[2] Univ Sao Paulo, Fac Med, Dept Surg, Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: LYMPHATIC RESEARCH AND BIOLOGY; NOV 2020.
• Citações Web of Science: 0

Resumo

Background: Chronic lymphedema is a common complication of lymphatic obstruction, particularly after cancer treatment, characterized by an increased volume of the affected extremity, partly caused by the accumulation of excessive adipose tissue. The relationship between lymph vessels' obstruction and fat deposit is, however, poorly understood. Objective: Our central hypothesis was that the inflammatory process caused by lymph stasis precedes the adipocyte differentiation and fat deposition. Methods and Results: We used a modified mouse tail model to produce secondary lymphedema. Animals were treated with dexamethasone, or the procedure was performed in nitric oxide synthase 2 (NOS2)-deficient mice to evaluate the role of inflammation in lymphedema formation. Adipose tissue (Lipin) and inflammatory markers (IL-6, MCP-1, and F4-80) were analyzed in histological samples and by quantitative polymerase chain reaction. We observed an increased deposition of fat into the affected area that starts 3 weeks after lymph vessel ligation; it further increased after 6 weeks. Genes involved in the inflammatory process were upregulated before adipocyte maturation. Treatment with dexamethasone or the use of inducible nitric oxide synthase knockout mice blocked the inflammatory reaction and inhibited the accumulation of fat distal to the lymphatic obstruction. Conclusion: In the modified mouse tail lymphedema, inflammation precedes adipogenesis. Our data suggest that MCP-1 and nitric oxide may be potential targets for lymphedema management. (AU)

• Processo FAPESP: 17/05232-8 - Interações entre inflamação e obesidade: mecanismos pelos quais o processo inflamatório influencia a adipogênese e as complicações da obesidade
• Beneficiário: Heraldo Possolo de Souza
• Modalidade de apoio: Auxílio à Pesquisa - Regular