Epigallocatechin gallate improves insulin resistance in HepG2 cells through alleviating inflammation and lipotoxicity.
AIMS
High levels of circulating free fatty acids (FFAs), inflammation and oxidative stress are important causes for insulin resistance (IR) and type 2 diabetes mellitus. The aim of this study was to investigate the mechanisms of EGCG in alleviating IR in HepG2 cells.


METHODS
HepG2 cells were treated with 25 mM glucose, 0.25 mM palmitic acid (PA), or 50 μM EGCG for 24 h.


RESULTS
EGCG increased glucose uptake and decreased glucose content. EGCG markedly decreased the levels of inflammatory and oxidative stress factors including nuclear factor κB (NF-κB), tumor necrosis factor-α, interleukin-6, reactive oxygen species, malondialdehyde and p53 protein, and markedly increased superoxide dismutases (SOD), glutathione peroxidase and SOD2 protein. EGCG significantly downregulated the levels of FFAs, triacylglycerol and cholesterol in HepG2 cells. The glucose transporter 2 (GLUT2) protein and its downstream proteins peroxisome proliferator-activated receptor γ coactivator (PGC)-1β were significantly increased, and sterol regulatory element-binding-1c (SREBP-1c) protein, and fatty acid synthase (FAS) were significantly decreased by EGCG in HepG2. Moreover, the foregoing effects were reversed by siRNA-mediated knockdown of GLUT2.


CONCLUSION
Our data demonstrated that EGCG improved IR, possibly through ameliorating glucose (25 mM) and PA (0.25 mM)-induced inflammation, oxidative stress, and FFAs via the GLUT2/PGC-1β/SREBP-1c/FAS pathway in HepG2 cells.
['Zhang|Qiao|Q|', 'Yuan|Hang|H|', 'Zhang|Cong|C|', 'Guan|Yue|Y|', 'Wu|Yuqing|Y|', 'Ling|Fan|F|', 'Niu|Yucun|Y|', 'Li|Ying|Y|']
D000818:Animals D002392:Catechin D003924:Diabetes Mellitus, Type 2 D005230:Fatty Acids, Nonesterified D056945:Hep G2 Cells D006801:Humans D007249:Inflammation D007333:Insulin Resistance D018384:Oxidative Stress D051381:Rats D014162:Transfection
Insulin resistance Inflammation Free fatty acids Oxidative stress EGCG