Abstract
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.
Highlights
Insulin resistance (IR) is a pathological state in which cells don’t respond to the normal physiological dose of insulin
The theaflavins mixture (TFs) concentrations used in the experiments were between 0–10 μg/mL, in order to explore whether TFs could influence cell insulin sensitivity at lower and safer doses
The 2-NBDG uptake of cells with insulin stimulation was reduced from 62.2 ± 4.9% to 27.7 ± 5.8% by Palmitic acid (PA) (150–350 μM). These results suggested that PA could stimulate IR in HepG2 cells without obvious cytotoxicity at 150–250 μM. 250 μM of PA and 500 nM of insulin were chosen for establishing IR HepG2 cell model and determining 2-NBDG uptake because of the higher efficiency
Summary
Insulin resistance (IR) is a pathological state in which cells don’t respond to the normal physiological dose of insulin. IR plays an important role in the pathogenesis of metabolic syndrome like obesity and type 2 diabetes mellitus (T2DM) [1]. Accumulating studies have certified that intake of high-calorie diets leads to the glycometabolic disorder and impairment of insulin sensitivity, which increase the risk of the development of metabolic abnormalities [2]. The current clinical drugs for treatment of diabetes and insulin resistance, including sulfonylureas, metformin and thiazolidinediones, always have some side effects such as weight gain and hypoglycemia [3,4,5]. The most popular tea in the world, has been found to effectively improve high-energy diet-induced metabolic syndromes such as hyperlipidemia, obesity, and diabetes in vivo [6,7].
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