Isoliquiritigenin impairs insulin signaling and adipocyte differentiation through the inhibition of protein-tyrosine phosphatase 1B oxidation in 3T3-L1 preadipocytes

• Published in: Food and chemical toxicology Vol. 93; pp. 5 - 12
• Main Authors: Park, Sun-Ji, Choe, Young-Geun, Kim, Jung-Hak, Chang, Kyu-Tae, Lee, Hyun-Shik, Lee, Dong-Seok
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.07.2016
• Subjects: 3T3-L1 Cells; 3T3-L1 preadipocytes; Adipocytes - cytology; Adipocytes - drug effects; Adipocytes - metabolism; Adipogenesis; Adipogenesis - drug effects; Animals; Blotting, Western; Cell Differentiation - drug effects; Chalcones - pharmacology; Enzyme Inhibitors - pharmacology; Gene Expression Regulation - drug effects; Hypoglycemic Agents - metabolism; Immunoprecipitation; Insulin - metabolism; Insulin signaling pathway; Isoliquritigenin; Lipids - chemistry; Mice; Oxidation-Reduction; Phosphatidylinositol 3-Kinases - metabolism; Phosphorylation - drug effects; Protein Tyrosine Phosphatase, Non-Receptor Type 1 - antagonists & inhibitors; Protein Tyrosine Phosphatase, Non-Receptor Type 1 - metabolism; Protein-tyrosine phosphatase 1B; Proto-Oncogene Proteins c-akt - metabolism; Reactive Oxygen Species - metabolism; Signal Transduction - drug effects; C/EBPα; ISL; Isoliquritigenin; IR; SOD; AKT; GR; IRS; H2O2; PPARγ; Insulin signaling pathway; FABP4/ aP2; 3T3-L1 preadipocytes; MDI; PTP1B; PI3K; Prx; ROS; Nox4; Protein-tyrosine phosphatase 1B; GLUT4; Adipogenesis
• ISSN: 0278-6915; 1873-6351
• DOI: 10.1016/j.fct.2016.04.017

Isoliquritigenin (ISL) is an abundant dietary flavonoid with a chalcone structure, which is an important constituent in Glycyrrhizae Radix (GR). ISL exhibits anti-oxidant activity, and this activity has been shown to play a beneficial role in various health conditions. However, it is unclear whether the anti-oxidant activity of ISL affects insulin signaling pathway and lipid accumulation of adipocytes. We sought to investigate the effects and molecular mechanisms of ISL on insulin-stimulated adipogenesis in 3T3-L1 cells. We investigated whether ISL attenuates insulin-induced Reactive Oxygen Species (ROS) generation, and whether ISL inhibits the lipid accumulation and the expression of adipogenic-genes during the differentiation of 3T3-L1 cells. ISL blocked the ROS generation, suppressed the lipid accumulation and the expression of adipocyte-specific proteins, which are increased in response to insulin stimulation during adipocyte differentiation of 3T3-L1 cells. We also investigated whether the anti-oxidant capacity of ISL is involved in regulating the molecular events of insulin-signaling cascade in 3T3-L1 adipocytes. ISL restores PTP1B activity by inhibiting PTP1B oxidation and IR/PI3K/AKT phosphorylation during the early stages of insulin-induced adipogenesis. Our findings show that the anti-oxidant capacity of ISL attenuated insulin IR/PI3K/AKT signaling through inhibition of PTP1B oxidation, and ultimately attenuated insulin-induced adipocyte differentiation of 3T3-L1 cells. [Display omitted] •ISL suppresses lipid accumulation and expression of adipogenic-gene expression in 3T3-L1 cells.•ISL blocks ROS generation that attenuates PTP1B oxidation and rescues PTP1B activity in the early stages of adipogenesis.•ISL restores PTP1B activation that inhibits the insulin IR/PI3K/AKT signaling, and differentiation of 3T3-L1 adipocytes.