title: Monounsaturated fatty acids are required for membrane translocation of protein kinase C-theta induced by lipid overload in skeletal muscle.
abstract: Protein kinase C (PKC) activation induced by diacylglycerols (DAGs) is one of the sequels of the dysregulation of intramuscular lipid metabolism and is thought to play an important role in the development of insulin resistance (IR). We tested the hypothesis that DAGs with different acyl chains have different biological effects and that DAG species enriched in monounsaturated fatty acids (MUFA) act as better activators of PKC. The experiments were performed in vitro on C2C12 myotubes treated with palmitate (16:0), stearate (18:0) or oleate (18:1) and in vivo on the skeletal muscles of rats fed high-fat (HF), high-tristearin (TS) or high-triolein (TO) diets. To define the importance of endogenously synthesized MUFA on DAG-induced PKCθ activation, we performed experiments on stearoyl-CoA desaturase 1 knockout mice (SCD1-/-) as well. The results show that the content of total DAGs and the levels of saturated DAG species are significantly increased in both insulin-resistant (16:0, HF and TO) and highly insulin-sensitive (18:0 and TS) groups. An increase in MUFA-containing DAGs levels was most constantly related to increase in PKCθ membrane translocation and IR. In the muscles of MUFA-deficient SCD1-/- mice, the DAG content and the induction of PKCθ translocation by the HF diet were significantly reduced. Collectively, our data from both the cell and animal experiments show that DAGs composed of 16:1 and/or 18:1, rather than the levels of total or saturated DAGs, are related to PKCθ membrane translocation. Moreover, our results show that the availability of dietary MUFA and/or the activity of endogenous desaturases play an important role in muscle DAG accumulation.
authors.affiliation: Laboratory of Cell Signaling and Metabolic Disorders, Nencki Institute of Experimental Biology, Warsaw, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Dziewulska
authors.forename: Pawel
authors.initials: P
authors.lastname: Dobrzyn
authors.forename: Magdalena
authors.initials: M
authors.lastname: Jazurek
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Pyrkowska
authors.forename: James M
authors.initials: JM
authors.lastname: Ntambi
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Dobrzyn
mesh_terms: D000818:Animals; D002460:Cell Line; D004041:Dietary Fats / Q000009:adverse effects / Q000494:pharmacology; D004075:Diglycerides / Q000235:genetics / Q000378:metabolism*; D005229:Fatty Acids, Monounsaturated / Q000378:metabolism* / Q000494:pharmacology; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism*; D050356:Lipid Metabolism / Q000187:drug effects / Q000235:genetics; D052439:Lipid Metabolism Disorders / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000473:pathology; D011493:Protein Kinase C / Q000235:genetics / Q000378:metabolism*; D000074121:Protein Kinase C-theta; D021381:Protein Transport / Q000187:drug effects / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D013230:Stearoyl-CoA Desaturase / Q000235:genetics / Q000378:metabolism
chemical_list: D004041:Dietary Fats; D004075:Diglycerides; D005229:Fatty Acids, Monounsaturated; D007527:Isoenzymes; C490333:Scd1 protein, mouse; D013230:Stearoyl-CoA Desaturase; C489593:Prkcq protein, mouse; C489591:Prkcq protein, rat; D011493:Protein Kinase C; D000074121:Protein Kinase C-theta