title: Perfluorooctane sulfonate-induced insulin resistance is mediated by protein kinase B pathway.
abstract: Perfluorooctane sulfonate (PFOS), a persistent organic pollutant, is blamed to be associated with the incidence of insulin resistance in the general human population. In this study, we found that PFOS inhibited the phosphorylation and activation of protein kinase B (AKT), a key mediator of cellular insulin sensitivity, in human hepatoma HepG2 cells. The mRNA level of the gluconeogenic gene PEPCK, a downstream target gene of AKT, was increased in PFOS-treated cells. Due to stimulated gluconeogenesis, insulin-stimulated glucose uptake was decreased in HepG2 cells. In our previous study, we found that PFOS disturbed autophagy in HepG2 cells. We proposed that PFOS could inhibit the activation of AKT through inhibiting mTORC2, a key regulator of autophagy. In this study, we found that the levels of triglyceride were increased in HepG2 cells. PFOS-induced accumulation of hepatic lipids also contributed to the inhibition of AKT. Eventually, the inhibition of AKT led to insulin resistance in PFOS-treated cells. Our data would provide new mechanistic insights into PFOS-induced hepatic insulin resistance.
authors.affiliation: Department of Occupational and Environmental Health, Dalian Medical University, 9 W Lushun South Road, Dalian 116044, PR China.
authors.forename: Tianming
authors.initials: T
authors.lastname: Qiu
authors.affiliation: Department of Occupational and Environmental Health, Dalian Medical University, 9 W Lushun South Road, Dalian 116044, PR China.
authors.forename: Min
authors.initials: M
authors.lastname: Chen
authors.affiliation: Department of Occupational and Environmental Health, Dalian Medical University, 9 W Lushun South Road, Dalian 116044, PR China.
authors.forename: Xiance
authors.initials: X
authors.lastname: Sun
authors.affiliation: Department of Occupational and Environmental Health, Dalian Medical University, 9 W Lushun South Road, Dalian 116044, PR China.
authors.forename: Jun
authors.initials: J
authors.lastname: Cao
authors.affiliation: Department of Occupational and Environmental Health, Dalian Medical University, 9 W Lushun South Road, Dalian 116044, PR China.
authors.forename: Chang
authors.initials: C
authors.lastname: Feng
authors.affiliation: Department of Occupational and Environmental Health, Dalian Medical University, 9 W Lushun South Road, Dalian 116044, PR China.
authors.forename: Dandan
authors.initials: D
authors.lastname: Li
authors.affiliation: Department of Occupational and Environmental Health, Dalian Medical University, 9 W Lushun South Road, Dalian 116044, PR China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wu
authors.affiliation: Liaoning Anti-Degenerative Diseases Natural Products Engineering Research Center, Dalian Medical University, 9 W Lushun South Road, Dalian 116044, PR China.
authors.forename: Liping
authors.initials: L
authors.lastname: Jiang
authors.affiliation: Department of Occupational and Environmental Health, Dalian Medical University, 9 W Lushun South Road, Dalian 116044, PR China. Electronic address: yaoxiaofeng@dmu.edu.cn.
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Yao
mesh_terms: D017738:Alkanesulfonic Acids / Q000008:administration & dosage*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D005466:Fluorocarbons / Q000008:administration & dosage*; D005947:Glucose / Q000493:pharmacokinetics; D056945:Hep G2 Cells; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance / Q000502:physiology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*
chemical_list: D017738:Alkanesulfonic Acids; D005466:Fluorocarbons; D007328:Insulin; C076994:perfluorooctane sulfonic acid; D051057:Proto-Oncogene Proteins c-akt; D005947:Glucose
keywords: Human liver HepG2 cells; Insulin resistance; Perfluorooctane sulfonate; Protein kinase B; Triglyceride