title: Rosiglitazone, but not epigallocatechin-3-gallate, attenuates the decrease in PGC-1α protein levels in palmitate-induced insulin-resistant C2C12 cells.
abstract: Alteration of lipid metabolism is an important mechanism for the treatment of insulin resistance. PGC-1α, a key regulator of mitochondrial biogenesis and function, plays an important role in the improvement of insulin sensitivity by increasing fatty acids β-oxidation. In the present study, the effects of epigallocatechin-3-gallate (EGCG), an anti-obesity agent and enhancer of lipid catabolism, on PGC-1α protein expression was examined and compared with anti-diabetic drug rosiglitazone (RGZ). After differentiation of C2C12 myoblasts to myotubes, insulin resistance was induced by palmitate treatment. Then the expression of the PGC-1a gene and glucose uptake were evaluated before and after treatment with RGZ and EGCG. Palmitate treatment significantly decreased PGC-1α protein expression in C2C12 cells (P < 0.05). RGZ could restore the expression of PGC-1α in palmitate treated cells (P > 0.05), while EGCG had no significant effect on the expression of this gene (P < 0.05). RGZ and EGCG significantly improved glucose uptake (by 2- and 1.54-fold, respectively) in myotubes treated with palmitate. These data suggest that RGZ and EGCG both exert their anti-diabetic activity by increasing insulin sensitivity, but with different molecular mechanisms. This effect of RGZ, unlike EGCG, is mediated, at least partly, by increasing PGC-1α protein expression.
authors.affiliation: Department of Anatomical Sciences, School of Medicine, Ilam University of Medical Sciences, Ilam, Iran.
authors.forename: Mohammad Hassan
authors.initials: MH
authors.lastname: Karimfar
authors.forename: Karimeh
authors.initials: K
authors.lastname: Haghani
authors.forename: Azar
authors.initials: A
authors.lastname: Babakhani
authors.forename: Salar
authors.initials: S
authors.lastname: Bakhtiyari
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D002392:Catechin / Q000031:analogs & derivatives / Q000494:pharmacology; D002460:Cell Line; D003402:Creatine Kinase / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007333:Insulin Resistance; D051379:Mice; D018485:Muscle Fibers, Skeletal / Q000166:cytology / Q000187:drug effects; D032446:Myoblasts / Q000166:cytology / Q000187:drug effects*; D010168:Palmitates / Q000378:metabolism; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000494:pharmacology*; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D000975:Antioxidants; D007004:Hypoglycemic Agents; D010168:Palmitates; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C485290:Ppargc1a protein, mouse; D045162:Thiazolidinediones; D014157:Transcription Factors; D000077154:Rosiglitazone; D002392:Catechin; C045651:epigallocatechin gallate; D003402:Creatine Kinase; D005947:Glucose