G13 signaling axis in the network of liver and muscle fuel consumption講演者：Prof. Sang Geon KIM 所属：College of Pharmacy, Dongguk University-Seoul
タイトル：G13 signaling axis in the network of liver and muscle fuel consumption
演 者：Prof. Sang Geon KIM (College of Pharmacy, Dongguk University-Seoul)
An imbalance between caloric intake and energy expenditure increases the risk of metabolic disorders, reducing life expectancy. Currently, there are limitations to the use of medications because of their lack of efficacy and considerable adverse outcomes. Given the diverse clinical problems and the growing worldwide epidemic, identification of novel targets for metabolic diseases is needed. In our lab, a hepatocyte-specific Ga13 knockout mouse line (Ga13 LKO) was created and utilized to explore the regulatory effects of Ga13 on systemic insulin sensitivity and the underlying basis. When subjected to high-fat diet model, Ga13 LKO mice exhibited defects in glucose uptake and insulin sensitivity in adipose tissue or skeletal muscle with no change in body weight gain. Inter-a-trypsin inhibitor HC1 (ITIH1) was identified as a secretory mediator governing insulin receptor desensitization in peripheral organs. Moreover, skeletal muscle is a major determinant of the systemic physiological status through the maintenance of energy homeostasis. Emerging evidence suggests that increases in mitochondrial mass, electron transfer uncoupling, and heat generation are critical processes necessary for the disease treatment. Therefore, the discovery of relevant signaling nodes and molecules could be an attractive strategy. In this research, we found a new physiological impact of the molecules that regulate mitochondrial biogenesis, thermogenesis in skeletal muscle, muscle type switch and muscle mass increase, and the consequent body weight decrease. The molecules include Ga13 and the downstream axis. In a separate study, we found USP21, which belongs to a family of deubiquitinases that mediate the removal and processing of ubiquitinated proteins, as a regulator of DNA-PKcs and ACLY. Our findings may expand the knowledge on oxidative myofiber type conversion, muscle mass control and thermogenic physiology involved in energy expenditure, providing an opportunity to develop new strategies to treat patients suffering from muscle problems and the associated metabolic diseases.
1: Kim YS, et al. Nature Communications, 2022 Oct 14;13(1):6080. doi:10.1038/s41467-022-33749-0.
2: Tak, J, et al. Theranostics, 2022, 12(4), 1570. doi:10.7150/thno.67722
3: A Kim et al. Journal of Cachexia, Sarcopenia and Muscle, 2021, doi:10.1002/jcsm.12777
4: Kim YS, et al. Hepatology. 2021 Apr;73(4):1307-1326. doi:10.1002/hep.31423. Epub 2021 Mar 16.
連絡先：大学院薬学研究院 生理学分野 加藤 (秦)
E-mail : email@example.com