title: Rosiglitazone increases fatty acid Δ9-desaturation and decreases elongase activity index in human skeletal muscle in vivo.
abstract: The ratio of unsaturated to saturated long-chain fatty acids (LC-FAs) in skeletal muscle has been associated with insulin resistance. Some animal data suggest a modulatory effect of peroxisome proliferator receptor γ (PPARγ) stimulation on stearoyl-CoA desaturase 1 (SCD1) and LC-FA composition in skeletal muscle, but human data are rare. We here investigate whether treatment with a PPARγ agonist affects myocellular SCD1 expression and modulates the intramyocellular fatty acid profile in individuals with impaired glucose tolerance. Muscle biopsies and hyperinsulinemic-euglycemic clamps were performed in 7 men before and after 8 weeks of rosiglitazone treatment. Intramyocellular saturated, monounsaturated, and polyunsaturated intramuscular fatty acid profiles were measured by gas chromatography. Effects on SCD1 messenger RNA expression were analyzed in C2C12 cells and in human biopsies before and after rosiglitazone treatment. As expected, treatment with the PPARγ activator rosiglitazone improved insulin sensitivity in humans. Myocellular SCD1 messenger RNA expression was increased in human biopsies and C2C12 cells. Although the total content of myocellular LC-FA was unchanged, a relative shift from saturated LC-FAs to unsaturated LC-FAs was observed in human biopsies. Particularly, the amount of stearate was reduced, whereas the amounts of palmitoleate as well as oleate and vaccenate were increased, after rosiglitazone therapy. These changes resulted in an increased fatty acid Δ9-desaturation index (16:1/16:0 and 18:1/18:0) in skeletal muscle and a decreased elongase activity index (18:0/16:0). The PPARγ associated phenotypes may be partially explained by an increased Δ9-desaturation and a decreased elongase activity of skeletal muscle.
authors: Department of Endocrinology, Diabetes and Nutrition, Charite-University Medicine Berlin, Campus Benjamin Franklin, Berlin, Germany.
authors: Knut
authors: K
authors: Mai
authors: Janin
authors: J
authors: Andres
authors: Thomas
authors: T
authors: Bobbert
authors: Anke
authors: A
authors: Assmann
authors: Katrin
authors: K
authors: Biedasek
authors: Sven
authors: S
authors: Diederich
authors: Ian
authors: I
authors: Graham
authors: Tony R
authors: TR
authors: Larson
authors: Andreas F H
authors: AF
authors: Pfeiffer
authors: Joachim
authors: J
authors: Spranger
mesh_terms: D000123:Acetyltransferases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002460:Cell Line; D000081031:Fatty Acid Elongases; D005227:Fatty Acids / Q000378:metabolism*; D005231:Fatty Acids, Unsaturated / Q000378:metabolism*; D005951:Glucose Tolerance Test / Q000379:methods; D006801:Humans; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance / Q000502:physiology; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism*; D047495:PPAR gamma / Q000819:agonists / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D000077154:Rosiglitazone; D013228:Stearates / Q000378:metabolism; D013230:Stearoyl-CoA Desaturase / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D051780:Sterol Regulatory Element Binding Protein 1 / Q000235:genetics / Q000378:metabolism; D045162:Thiazolidinediones / Q000494:pharmacology*
chemical_list: D005227:Fatty Acids; D005231:Fatty Acids, Unsaturated; D007328:Insulin; D047495:PPAR gamma; D012333:RNA, Messenger; C497387:SREBF1 protein, human; D013228:Stearates; D051780:Sterol Regulatory Element Binding Protein 1; D045162:Thiazolidinediones; D000077154:Rosiglitazone; C523776:SCD1 protein, human; C490333:Scd1 protein, mouse; D013230:Stearoyl-CoA Desaturase; D000123:Acetyltransferases; D000081031:Fatty Acid Elongases