title: SIRT1 attenuates palmitate-induced endoplasmic reticulum stress and insulin resistance in HepG2 cells via induction of oxygen-regulated protein 150.
abstract: Endoplasmic reticulum (ER) stress has been implicated in the pathology of type 2 diabetes mellitus (T2DM). Although SIRT1 has a therapeutic effect on T2DM, the mechanisms by which SIRT1 ameliorates insulin resistance (IR) remain unclear. In this study, we investigated the impact of SIRT1 on palmitate-induced ER stress in HepG2 cells and its underlying signal pathway. Treatment with resveratrol, a SIRT1 activator significantly inhibited palmitate-induced ER stress, leading to the protection against palmitate-induced ER stress and insulin resistance. Resveratrol and SIRT1 overexpression induced the expression of oxygen-regulated protein (ORP) 150 in HepG2 cells. Forkhead box O1 (FOXO1) was involved in the regulation of ORP150 expression because suppression of FOXO1 inhibited the induction of ORP150 by SIRT1. Our results indicate a novel mechanism by which SIRT1 regulates ER stress by overexpression of ORP150, and suggest that SIRT1 ameliorates palmitate-induced insulin resistance in HepG2 cells via regulation of ER stress.
authors.affiliation: GMS (Genetic Diagnosis & Molecular Medical Science) Research Center, Dr. Lee's OB & GYN Clinic, Seoul, Republic of Korea.
authors.forename: Tae Woo
authors.initials: TW
authors.lastname: Jung
authors.forename: Kyoung-Tae
authors.initials: KT
authors.lastname: Lee
authors.forename: Myung Won
authors.initials: MW
authors.lastname: Lee
authors.forename: Kang-Hyeon
authors.initials: KH
authors.lastname: Ka
mesh_terms: D059865:Endoplasmic Reticulum Stress / Q000187:drug effects / Q000502:physiology*; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors / Q000378:metabolism; D018840:HSP70 Heat-Shock Proteins; D056945:Hep G2 Cells; D006801:Humans; D007333:Insulin Resistance; D010168:Palmitates / Q000378:metabolism* / Q000494:pharmacology; D011506:Proteins / Q000819:agonists / Q000235:genetics / Q000378:metabolism*; D000077185:Resveratrol; D056564:Sirtuin 1 / Q000378:metabolism*; D013267:Stilbenes
chemical_list: C085126:FOXO1 protein, human; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors; D018840:HSP70 Heat-Shock Proteins; D010168:Palmitates; D011506:Proteins; D013267:Stilbenes; C050087:oxygen-regulated proteins; C447939:SIRT1 protein, human; D056564:Sirtuin 1; D000077185:Resveratrol