title: Reduction of endoplasmic reticulum stress using chemical chaperones or Grp78 overexpression does not protect muscle cells from palmitate-induced insulin resistance.
abstract: Endoplasmic reticulum (ER) stress is proposed as a novel link between elevated fatty acids levels, obesity and insulin resistance in liver and adipose tissue. However, it is unknown whether ER stress also contributes to lipid-induced insulin resistance in skeletal muscle, the major tissue responsible of insulin-stimulated glucose disposal. Here, we investigated the possible role of ER stress in palmitate-induced alterations of insulin action, both in vivo, in gastrocnemius of high-palm diet fed mice, and in vitro, in palmitate-treated C(2)C(12) myotubes. We demonstrated that 8 weeks of high-palm diet increased the expression of ER stress markers in muscle of mice, whereas ex-vivo insulin-stimulated PKB phosphorylation was not altered in this tissue. In addition, exposure of C(2)C(12) myotubes to either tuncamycine or palmitate induced ER stress and altered insulin-stimulated PKB phosphorylation. However, alleviation of ER stress by either TUDCA or 4-PBA treatments, or by overexpressing Grp78, did not restore palmitate-induced reduction of insulin-stimulated PKB phosphorylation in C(2)C(12) myotubes. This work highlights that, even ER stress is associated with palmitate-induced alterations of insulin signaling, ER stress is likely not the major culprit of this effect in myotubes, suggesting that the previously proposed link between ER stress and insulin resistance is less important in skeletal muscle than in adipose tissue and liver.
authors.affiliation: INSERM UMR-1060, CarMeN Laboratory, Lyon 1 University, Rockefeller Medical Faculty and Charles Merieux Lyon-Sud Medical School, Lyon, France. jennifer.rieusset@univ-lyon1.fr
authors.forename: Jennifer
authors.initials: J
authors.lastname: Rieusset
authors.forename: Marie-Agnès
authors.initials: MA
authors.lastname: Chauvin
authors.forename: Annie
authors.initials: A
authors.lastname: Durand
authors.forename: Amélie
authors.initials: A
authors.lastname: Bravard
authors.forename: Fabienne
authors.initials: F
authors.lastname: Laugerette
authors.forename: Marie-Caroline
authors.initials: MC
authors.lastname: Michalski
authors.forename: Hubert
authors.initials: H
authors.lastname: Vidal
mesh_terms: D000818:Animals; D002082:Butylamines / Q000494:pharmacology; D004032:Diet / Q000009:adverse effects*; D004041:Dietary Fats / Q000008:administration & dosage / Q000009:adverse effects* / Q000494:pharmacology; D000091342:Endoplasmic Reticulum Chaperone BiP; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D006360:Heat-Shock Proteins / Q000096:biosynthesis* / Q000235:genetics; D007328:Insulin / Q000378:metabolism / Q000494:pharmacology; D007333:Insulin Resistance; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018485:Muscle Fibers, Skeletal / Q000187:drug effects / Q000502:physiology*; D010168:Palmitates / Q000008:administration & dosage / Q000009:adverse effects* / Q000494:pharmacology; D013655:Taurochenodeoxycholic Acid / Q000494:pharmacology; D014415:Tunicamycin / Q000494:pharmacology
chemical_list: C121358:4-phenylbutylamine; D002082:Butylamines; D004041:Dietary Fats; D000091342:Endoplasmic Reticulum Chaperone BiP; D006360:Heat-Shock Proteins; C000717248:Hspa5 protein, mouse; D007328:Insulin; D010168:Palmitates; D014415:Tunicamycin; D013655:Taurochenodeoxycholic Acid; C031655:ursodoxicoltaurine