The Role of Thada in Energy Homeostasis ...

• Main Author: Lin, Yu-Hung
• Format: Thesis
• Language: English
• Published: Apollo - University of Cambridge Repository 2022
• Subjects: Thermogenesis; skeletal muscle; cold exposure; obesity; energy homeostasis; Arctic
• Online Access: https://dx.doi.org/10.17863/cam.91910; https://www.repository.cam.ac.uk/handle/1810/344487

The high prevalence of obesity worldwide has fuelled research to discover new treatments that tackle obesity safely and effectively. Over the last decades, we and others have considered that developing strategies focused on increasing organismal energy expenditure may help fight obesity and its associated comorbidities. For this purpose, our research focused on a gene called Thada. THADA encodes a 220 kDa protein that has been recently reported in Drosophila melanogaster to uncouple the heat dissipation of SERCA from its Ca2+ pumping action. We anticipated that this mechanism could contribute significantly to the energy metabolism in endotherms, such as mammals. We envisaged THADA could contribute to the muscle non-shivering thermogenesis—in addition to sarcolipin, another uncoupler of SERCA. Our working hypothesis was reinforced by the fact that mutations in THADA have been positively selected during the last 45-30K years in the Arctic populations, which the authors of the research and we interpret as a ...