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

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.

Four sesquiterpene glycosides from loquat (Eriobotrya japonica) leaf ameliorates palmitic acid-induced insulin resistance and lipid accumulation in HepG2 Cells via AMPK signaling pathway

“…Studies pointed out that glucose uptake assay in IR cells determined whether compounds could ameliorate IR in HepG2 cells induced by PA (Tong et al, 2018). As shown in Figs.…”

Antidiabetic Effects of Flavan-3-ols and Their Microbial Metabolites

“…A mixture of TF, theaflavin-3-gallate (TF-3-G), theaflavin-3′-gallate (TF-3′-G), and theaflavin-3,3′-digallate (TFDG) (2.5–10 µg/mL, 24 h treatment) improved IRes induced by palmitic acid in HepG2 cells, as measured by the increase in 2-(N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)-2-deoxyglucose (2-NBDG) uptake using metformin as a positive control [ 24 ]. Total GLUT4 and protein levels of GLUT4 bound to the membrane were increased by theaflavins in a dose-dependent manner [ 24 ]. They reversed the reduction of the phosphorylation level of Akt induced by palmitic acid and led to an increased phosphorylation of IRS-1 (Ser307) in HepG2 cells [ 24 ].…”

“…Total GLUT4 and protein levels of GLUT4 bound to the membrane were increased by theaflavins in a dose-dependent manner [ 24 ]. They reversed the reduction of the phosphorylation level of Akt induced by palmitic acid and led to an increased phosphorylation of IRS-1 (Ser307) in HepG2 cells [ 24 ].…”

Remedying the Mitochondria to Cure Human Diseases by Natural Products

“…Polysaccharides from Portulaca oleracea L. [70] Korean red ginseng [71] Berberine [72] Quercetin [73] Theaflavins [74] Puerarin [76] Mitochondrial membrane potential imbalance Polysaccharides from Portulaca oleracea L. [70] Silibinin [75]…”

“…Silibinin [75] Mitochondrial fusion, division, and autophagy Korean red ginseng [71] Quercetin [73] Theaflavins [74] Silibinin [75] Puerarin [76] Diabetes complications…”