title: TiO2 nanoparticles induce insulin resistance in liver-derived cells both directly and via macrophage activation.
abstract: Upon exposure, TiO(2) nanoparticles (NPs) have been recovered in internal organs such as the liver, and are proposed to cause cellular/organ dysfunction, particularly in the liver and lungs. We hypothesized that despite being considered "inert" as bulk material, TiO(2) NPs may impair insulin responses in liver-derived cells, either indirectly by inflammatory activation of macrophages, and/or by directly interfering with insulin signaling. Using qRT-PCR and conditioned medium (CM) approaches, we show that exposure to TiO(2) NPs activates macrophages' expression of TNF-α, IL-6, IL-8, IL-1α and IL-1β and the resulting CM induces insulin resistance in Fao cells. Furthermore, direct exposure of Fao cells to TiO(2) results in activation of the stress kinases JNK and p38MAP kinase, and in induction of insulin resistance at the signaling and metabolic levels. Collectively, our findings provide a proof-of-concept for the ability of man-made NPs to induce insulin resistance in liver-derived cells, an endocrine abnormality underlying some of the most common human diseases.
authors: Department of Environmental Sciences, The Weizmann Institute of Science, Rehovot, Israel.
authors: Diana
authors: D
authors: Gurevitch
authors: Timor
authors: T
authors: Shuster-Meiseles
authors: Ori
authors: O
authors: Nov
authors: Yehiel
authors: Y
authors: Zick
authors: Assaf
authors: A
authors: Rudich
authors: Yinon
authors: Y
authors: Rudich
mesh_terms: D000818:Animals; D015153:Blotting, Western; D045744:Cell Line, Tumor; D017077:Culture Media, Conditioned; D006003:Glycogen / Q000096:biosynthesis; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance; D008099:Liver / Q000187:drug effects*; D008262:Macrophage Activation; D053768:Metal Nanoparticles / Q000633:toxicity*; D051381:Rats; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction; D014025:Titanium / Q000633:toxicity*
chemical_list: D017077:Culture Media, Conditioned; D007328:Insulin; C009495:titanium dioxide; D006003:Glycogen; D014025:Titanium