Evaluation of beige adipocyte induction by cancer-associated cachexia in adipocytes knockout for TLR4

• Grant number: 19/13983-9
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Effective date (Start): September 01, 2019
• Effective date (End): August 31, 2020
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Miguel Luiz Batista Junior
• Grantee: Luís Felipe Galvão Valdivia
• Host Institution: Pró-Reitoria Acadêmica. Universidade de Mogi das Cruzes (UMC). Campus da Sede Mogi das Cruzes. Mogi das Cruzes , SP, Brazil

Abstract

Cachexia is a multifactorial syndrome, related to systemic inflammation, metabolic chaos and especially with the continuous reduction of adipose and skeletal muscle mass. Adipose tissue (TA) is early affected by the syndrome and plays an important role in its development. It is considered a heterogeneous organ divided into white TA (TAB) and brown TA (TAM), each with its distinct morphological and metabolic characteristics. The remodeling of TA is the final result of a set of morphofunctional changes that affect this tissue. Recently, browning has been identified as the main remodeling process of TA, contributing to the evolution of the cachectic condition due to excessive energy expenditure and increased lipolysis rates. However, little is known about its origin. There are indications suggesting that the increase of the inflammatory processes due to the high release of cytokines secreted by the tumor and the TA are potential causes of this phenomenon. Studies from our research group showed that animals knockouts to systemic TLR4 reduced inflammatory activity and attenuated the browning process. Consequently, it mitigates the effects of cachexia associated with cancer. The hypothesis of the present study is that TLR4 is directly involved in the development of cancer-associated cachexia and remodeling of AT. In this sense, we aim to evaluate the adipocyte-specific deletion of TLR4 in the thermogenic, inflammatory and morphological profile in animals with tumor with induced cachexia.