Screening of flavor compounds using Ucp1-luciferase reporter beige adipocytes identified 5-methylquinoxaline as a novel UCP1-inducing compound

Uncoupling protein 1 (UCP1) in brown or beige adipocytes is a mitochondrial protein that is expected to enhance whole-body energy expenditure. For the high-throughput screening of UCP1 transcriptional activity regulator, we established a murine inguinal white adipose tissue-derived Ucp1-luciferase reporter preadipocyte line. Using this reporter preadipocyte line, 654 flavor compounds were screened, and a novel Ucp1 expression-inducing compound, 5-methylquinoxaline, was identified. Adipocytes treated with 5-methylquinoxaline showed increased Ucp1 mRNA expression levels and enhanced oxygen consumption. 5-Methylquinoxaline induced Ucp1 expression through peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC1 alpha), and 5-methylquinoxaline-induced PGC1 alpha activation seemed to be partially regulated by its phosphorylation or deacetylation. Thus, our Ucp1-luciferase reporter preadipocyte line is a useful tool for screening of Ucp1 inductive compounds.

Automated summary

In this study, a Ucp1-luciferase reporter preadipocyte line was established for screening Ucp1-inductive compounds. A novel compound, 5-methylquinoxaline, was identified as an inducer of Ucp1 expression through the PGC1α pathway, leading to increased oxygen consumption. This reporter preadipocyte line can be a useful tool for identifying other Ucp1 inducers.