Subcutaneous adipose tissue formation mechanisms in a lymphedema experimental model

• Grant number: 16/04256-8
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: April 01, 2016
• End date: December 31, 2017
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Heraldo Possolo de Souza
• Grantee: Guilherme de Arruda Cuadrado
• Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 13/07607-8 - OCRC - Obesity and Comorbidities Research Center, AP.CEPID

Abstract

The increase in the adipose subcutaneous tissue is related to very prevalent diseases such as obesity and the lymphedema secondary to lymphatic obstruction (most commonly associated to cancer treatment). Recently, it was developed an experimental model in which the lymphatic vessels blockage in the proximal portion of mice tails leads to the development of subcutaneous deposits of fat, very similar to the ones observed in human beings. This is, therefore, a great model to study the adipogenesis and lymphedema. This way, our main objective will be to determine the molecular and cellular mechanisms by which lymphatic stasis take to the accumulation of adipose tissue and to test whether the low-level laser therapy is capable to inhibit this fenomenon. Initially it will be establish the model of adipogenesis in C57BL6 mice and genetically-modified ones. It will be made an incision around the proximal third of the tail and the blockage of local lymphatic vessels. About 6 weeks after the procedure, it occurs the formation of mensurable amount of adipose tissue ahead of the lesion. It will be evaluated the signaling pathways involved in adipogenesis through the RT-PCR and immunohistochemistry, with special attention to the inflammatory mechanisms. As to elucidate the mechanisms involved in adipogenesis, this study will be able to be completed repeating the procedure in deficient mice:-in toll-like receptor 4 (TLR4-/-) to determine the role of innate immunity;-nude, to determine the role of T lymphocytes;-PGC-1 (alpha e beta);-in NOS2, to determine the role of nitric oxyde. Furthermore, in previous studies in our lab, we demonstrated the low-level laser therapy (LLLT) can reduce the expression of PPAR-g. Knowing that PPAR-g is one of the main transcription factors involved in the differentiation of pre-adipocytes in adipocytes, we made the hypothesis the LLLT could reduce adipogenesis. Therefore, a group of animals will have their tail irradiated with LLLT and the formation of adipose tissue will be observed in both groups. We believe the data obtained in this study can be useful in the development of effective treatment in obesity and after lymphatic obstruction lymphedema, pathological situation of high prevalence. (AU)