Journal of Nutrition and Health

The Korean Nutrition Society (한국영양학회)
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Effects of isorhamnetin on the regulation of mitochondrial function in C2C12 muscle cells

Isorhamnetin의 근육세포 미토콘드리아 기능조절에 미치는 효과

  • Lee, Mak-Soon (Department of Nutritional Science and Food Management, Ewha Womans University) ;
  • Kim, Yangha (Department of Nutritional Science and Food Management, Ewha Womans University)
  • 이막순 (이화여자대학교 식품영양학과) ;
  • 김양하 (이화여자대학교 식품영양학과)
  • Received : 2021.07.14
  • Accepted : 2021.08.13
  • Published : 2021.08.31
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Abstract

Purpose: Muscle mitochondria play a key role in regulating fatty acid and glucose metabolism. Dysfunction of muscle mitochondria is associated with metabolic diseases such as obesity and type 2 diabetes. Isorhamnetin (ISOR), also known as 3-O-methylquercetin, a quercetin metabolite, is a naturally occurring flavonoid in many plants. This study evaluated the effects of ISOR on the regulation of the mitochondrial function of C2C12 muscle cells. Methods: C2C12 muscle cells were differentiated for 5 days, and then treated in various concentrations of ISOR. Cytotoxicity was determined by assessing cell viability using the water-soluble tetrazolium salt-8 assay principle at different concentrations of ISOR and time points. Levels of the mitochondrial DNA (mtDNA) content and gene expression were measured by quantitative real-time polymerase chain reaction. The citrate synthase (CS) activity was quantified by the enzymatic method. Results: ISOR at a concentration of 10 µM did not show any cytotoxic effects. ISOR increased the mtDNA copy number in a time- or dose-dependent manner. The messenger RNA levels of genes involved in mitochondrial function, such as peroxisome proliferator-activated receptor-γ coactivator-1α, and uncoupling protein 3 were significantly stimulated by the ISOR treatment. The CS activity was also significantly increased in a time- or dose-dependent manner. Conclusion: These results suggest that ISOR enhances the regulation of mitochondrial function, which was at least partially mediated via the stimulation of the mtDNA replication, mitochondrial gene expression, and CS activity in C2C12 muscle cells. Therefore, ISOR may be useful as a potential food ingredient to prevent metabolic diseases-associated muscle mitochondrial dysfunction.

Keywords

Acknowledgement

This study was supported by the National Research Foundation of Korea (NRF) funded by the Korean Government (MSIT) (No. 2019R1A2C1002861).

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