Isoliquiritigenin impairs insulin signaling and adipocyte differentiation through the inhibition of protein-tyrosine phosphatase 1B oxidation in 3T3-L1 preadipocytes.
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.
School of Life Science, KNU Creative BioResearch Group (BK21 Plus Project) and Biotechnology, Kyungpook National University, Daegu 41566, Republic of Korea; Renal Division, School of Medicine, Washington University in St Louis, Missouri, USA.
Sun-Ji
SJ
Park
School of Life Science, KNU Creative BioResearch Group (BK21 Plus Project) and Biotechnology, Kyungpook National University, Daegu 41566, Republic of Korea.
Young-Geun
YG
Choe
School of Life Science, KNU Creative BioResearch Group (BK21 Plus Project) and Biotechnology, Kyungpook National University, Daegu 41566, Republic of Korea.
Jung-Hak
JH
Kim
National Primate Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, Republic of Korea.
Kyu-Tae
KT
Chang
School of Life Science, KNU Creative BioResearch Group (BK21 Plus Project) and Biotechnology, Kyungpook National University, Daegu 41566, Republic of Korea.
Hyun-Shik
HS
Lee
School of Life Science, KNU Creative BioResearch Group (BK21 Plus Project) and Biotechnology, Kyungpook National University, Daegu 41566, Republic of Korea. Electronic address: lee1@knu.ac.kr.
Dong-Seok
DS
Lee
D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D050156:Adipogenesis / Q000187:drug effects; D000818:Animals; D015153:Blotting, Western; D002454:Cell Differentiation / Q000187:drug effects*; D047188:Chalcones / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects*; D007004:Hypoglycemic Agents / Q000378:metabolism; D047468:Immunoprecipitation; D007328:Insulin / Q000378:metabolism*; D008055:Lipids / Q000737:chemistry; D051379:Mice; D010084:Oxidation-Reduction; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
D047188:Chalcones; D004791:Enzyme Inhibitors; D007004:Hypoglycemic Agents; D007328:Insulin; D008055:Lipids; D017382:Reactive Oxygen Species; C040920:isoliquiritigenin; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1
3T3-L1 preadipocytes; Adipogenesis; Insulin signaling pathway; Isoliquritigenin; Protein-tyrosine phosphatase 1B