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Theaflavins Improve Insulin Sensitivity through Regulating Mitochondrial Biosynthesis in Palmitic Acid-Induced HepG2 Cells

by Tuantuan Tong 1,2,†, Ning Ren 1,2,†, Park Soomi 1,2, Jiafan Wu 1,2, Na Guo 1,2, Hyunuk Kang 1,2, Eunhye Kim 1,2, Yuanyuan Wu 1,2, Puming He 1,2, Youying Tu 1,2,* and Bo Li 1,2,*
1
Department of Tea Science, Zhejiang University, 866 Yuhangtang Road, Hangzhou 310058, China;[email protected] (T.T.)
2
Tea Research Institute, Zhejiang University, 866 Yuhangtang Road, Hangzhou 310058, China
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work and are considered as co-first authors.
Molecules 2018, 23(12), 3382; https://doi.org/10.3390/molecules23123382
Received: 12 November 2018 / Revised: 16 December 2018 / Accepted: 17 December 2018 / Published: 19 December 2018
Theaflavins, the characteristic and bioactive polyphenols in black tea, possess the potential improving effects on insulin resistance-associated metabolic abnormalities, including obesity and type 2 diabetes mellitus. However, the related molecular mechanisms are still unclear. In this research, we investigated the protective effects of theaflavins against insulin resistance in HepG2 cells induced by palmitic acid. Theaflavins significantly increased glucose uptake of insulin-resistant cells at noncytotoxic doses. This activity was mediated by upregulating the total and membrane bound glucose transporter 4 protein expressions, increasing the phosphor-Akt (Ser473) level, and decreasing the phosphorylation of IRS-1 at Ser307. Moreover, theaflavins were found to enhance the mitochondrial DNA copy number, down-regulate the PGC-1β mRNA level and increase the PRC mRNA expression. Mdivi-1, a selective mitochondrial division inhibitor, could attenuate TFs-induced promotion of glucose uptake in insulin-resistant HepG2 cells. Taken together, these results suggested that theaflavins could improve hepatocellular insulin resistance induced by free fatty acids, at least partly through promoting mitochondrial biogenesis. Theaflavins are promising functional food ingredients and medicines for improving insulin resistance-related disorders. View Full-Text
Keywords: theaflavins; hepatocyte; insulin resistance; insulin signaling pathway; mitochondrial biogenesis; peroxisome proliferator-activated receptor coactivator-1 (PGC-1) theaflavins; hepatocyte; insulin resistance; insulin signaling pathway; mitochondrial biogenesis; peroxisome proliferator-activated receptor coactivator-1 (PGC-1)
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Tong, T.; Ren, N.; Soomi, P.; Wu, J.; Guo, N.; Kang, H.; Kim, E.; Wu, Y.; He, P.; Tu, Y.; Li, B. Theaflavins Improve Insulin Sensitivity through Regulating Mitochondrial Biosynthesis in Palmitic Acid-Induced HepG2 Cells. Molecules 2018, 23, 3382.

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