Publication: Pyruvate carboxylase supports basal ATP-linked respiration in human pluripotent stem cell-derived brown adipocytes
Issued Date
2021-09-10
Resource Type
ISSN
10902104
0006291X
0006291X
Other identifier(s)
2-s2.0-85109170347
Rights
Mahidol University
Rights Holder(s)
SCOPUS
Bibliographic Citation
Biochemical and Biophysical Research Communications. Vol.569, (2021), 139-146
Suggested Citation
Udom Lao-On, Timothy S. Cliff, Stephen Dalton, Sarawut Jitrapakdee Pyruvate carboxylase supports basal ATP-linked respiration in human pluripotent stem cell-derived brown adipocytes. Biochemical and Biophysical Research Communications. Vol.569, (2021), 139-146. doi:10.1016/j.bbrc.2021.06.096 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/76027
Research Projects
Organizational Units
Authors
Journal Issue
Thesis
Title
Pyruvate carboxylase supports basal ATP-linked respiration in human pluripotent stem cell-derived brown adipocytes
Other Contributor(s)
Abstract
Brown adipocytes (BA) are a specialized fat cell which possesses a high capacity for fuel oxidation combined with heat production. The maintenance of high metabolic activity in BA requires elevated oxidation of fuel through the tricarboxylic acid cycle. Pyruvate carboxylase (PC) was previously proposed to be essential for coordination between fuel oxidation and thermogenesis. By differentiating human pluripotent stem cells to mature BA in vitro, we showed that ablation of PC gene by CRISPR Cas9 genome engineering did not impair the ability of stem cells to generate mature BA. However, brown adipocytes deficient for PC expression displayed a 35% reduction in ATP-linked respiration, but not thermogenesis under both basal and isoproterenol-stimulated conditions. This relatively mild impairment of ATP-link respiration in PC knockout BA was protected by increased spare mitochondrial respiratory capacity. Taken together, this study highlights the role of PC in supporting fuel oxidation rather than thermogenesis in human BA.