TRPA1 channel as a modulator of cancer-associated cachexia in mice (Mus musculus)

• Grant number: 24/05262-8
• Support Opportunities: Scholarships in Brazil - Master
• Effective date (Start): September 01, 2024
• Effective date (End): January 31, 2026
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Ana Maria de Lauro Castrucci
• Grantee: Letícia Menezes Vasconcelos
• Host Institution: Instituto de Biociências (IB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 17/24615-5 - Breaking a paradigm? Melanopsin, a canonical photo-pigment, acting as sensor to entrain the clock in light unexposed organs, and its putative interaction with TRP channels: a trans-disciplinary study involving physiological and pathological aspects, AP.TEM

Abstract

Cancer cachexia is present in around 80% of advanced cases, being responsible for more than 20% of cancer deaths. A complex metabolic syndrome, cachexia is characterized by the continuous loss of skeletal muscle mass and depletion of fat stores and it is often associated with anorexia and systemic inflammation, among other disorders. Despite great interest, therapy options are limited due to the heterogeneous profile of the syndrome. Pro-inflammatory cytokines, specifically IL-6 and TNF±, have been targets in the search for mediators of cachexia. However, treating each one of them does not seem to result in sufficient benefits to reverse the syndrome, implying the existence of cooperation between the mediators. Early morphofunctional changes in white adipose tissue (WAT), such as the browning effect, are reported in the literature, an effect associated with increased expression of UCP1 responsible for thermogenesis. Adittionally, recent studies presented the potential contribution of brown adipose tissue (BAT) to energy expenditure during the development of cachexia. The TRP channels are receiving great attention in studies with a pathological focus, due to their involvement in a diversity of sensations. Our group has been highlighting the role of the TRPA1 channel in thermogenic and metabolic regulation in obese animals on a high-fat diet (HFD), in which the absence of the channel negatively influenced weight gain and contributed to a better inflammatory condition. Based on the data above, the proposal is to evaluate the role of the TRPA1 channel in the development and modulation of cancer-associated cachexia associated in response to different temperatures. Using morphological analyses, hormonal measurements, behavioral monitoring and molecular biology techniques we will evaluate the functioning of signaling pathways in healthy and cachetic wild type and Trpa1 knockout animals subjected to different thermal stresses.