Role of TRPA1 in human thermogenesis: a promising approach for obesity treatment?

• Grant number: 24/06651-8
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• Start date: September 27, 2024
• End date: September 26, 2025
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Ana Maria de Lauro Castrucci
• Grantee: Cristhian David Sua Cespedes
• Supervisor: Yu-Hua Tseng
• Host Institution: Instituto de Biociências (IB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Institution abroad: Harvard University, Boston, United States
• Associated to the scholarship: 22/04584-6 - ROLE OF THE TRANSIENT RECEPTOR POTENTIAL CHANNEL TRPA1 IN OBESITY. A NEW THERAPEUTIC TARGET?, BP.DR

Abstract

Obesity is generally defined as the abnormal or excessive accumulation of fat (adipose tissue), resulting in several health risks. Overweight and obesity can trigger metabolic disorders such as diabetes and its associated conditions as well as heart disease and cerebrovascular accidents (one of the main causes of death worldwide). Transient potential channels (TRP) appear to be one of the main players involved in thermal sensation in vertebrates. Also, results from genome scans for obesity have suggested that several TRP channels may be associated with obesity and have been described in obesity-related diseases such as diabetes, dyslipidemia, hypertension, and atherosclerosis; however, there is a lack of knowledge regarding the role of TRPA1 in these processes in humans and animals. The activation of brown adipose tissue (BAT) has been considered an attractive approach for the treatment or prevention of obesity and related metabolic alterations. However, the majority of studies have employed animal models (mainly rodents) with extremely significant results that cannot always be associated with the functioning of human adipocytes, due to the differences between species. Based on the knowledge available in the literature, the question arises whether the TRPA1 channel may be involved in non-canonical processes related to the regulation of thermogenesis and obesity in humans. Our aim will be to evaluate the role of this channel in human wild type (WT) and TRPA1-/- knockout adipocytes under pharmacological stimulation of the thermogenesis pathway to mimic cold exposure in vivo.