title: Direct inhibitory effects of pioglitazone on hepatic fetuin-A expression.
abstract: Fetuin-A, a circulating glycoprotein synthesized in the liver, is involved in insulin resistance and type 2 diabetes. However, regulation of fetuin-A synthesis has remained obscure. We previously reported that pioglitazone treatment significantly reduced serum fetuin-A levels in patients with type 2 diabetes. To clarify whether pioglitazone can directory inhibit hepatic fetuin-A synthesis, we investigated the effects of pioglitazone on fetuin-A expression both in vitro and in vivo. Pioglitazone treatment suppressed mRNA and protein expression of fetuin-A in Fao hepatoma cells. Interestingly, rosiglitazone but not metformin, also inhibited fetuin-A expression. In addition, GW 9662, an inhibitor of peroxisome proliferator-activated receptor (PPAR) γ, reversed pioglitazone-induced suppression of fetuin-A, suggesting that thiazolidinedione derivatives may have common characteristics with regard to fetuin-A suppression, possibly through PPARγactivation. Finally, oral administration of pioglitazone to mice for 8 weeks resulted in suppression of hepatic fetuin-A mRNA. These findings suggest that pioglitazone may partially ameliorate insulin resistance through its direct inhibitory effects on fetuin-A expression in the liver.
authors.affiliation: Department of Metabolism, Endocrinology and Molecular Medicine, Osaka City University Graduate School of Medicine, Osaka, Japan.
authors.forename: Akinobu
authors.initials: A
authors.lastname: Ochi
authors.affiliation: Department of Metabolism, Endocrinology and Molecular Medicine, Osaka City University Graduate School of Medicine, Osaka, Japan.
authors.forename: Katsuhito
authors.initials: K
authors.lastname: Mori
authors.affiliation: Department of Metabolism, Endocrinology and Molecular Medicine, Osaka City University Graduate School of Medicine, Osaka, Japan.
authors.forename: Masanori
authors.initials: M
authors.lastname: Emoto
authors.affiliation: Department of Metabolism, Endocrinology and Molecular Medicine, Osaka City University Graduate School of Medicine, Osaka, Japan.
authors.forename: Shinya
authors.initials: S
authors.lastname: Nakatani
authors.affiliation: Department of Metabolism, Endocrinology and Molecular Medicine, Osaka City University Graduate School of Medicine, Osaka, Japan.
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Morioka
authors.affiliation: Department of Metabolism, Endocrinology and Molecular Medicine, Osaka City University Graduate School of Medicine, Osaka, Japan.
authors.forename: Koka
authors.initials: K
authors.lastname: Motoyama
authors.affiliation: Department of Metabolism, Endocrinology and Molecular Medicine, Osaka City University Graduate School of Medicine, Osaka, Japan.
authors.forename: Shinya
authors.initials: S
authors.lastname: Fukumoto
authors.affiliation: Department of Metabolism, Endocrinology and Molecular Medicine, Osaka City University Graduate School of Medicine, Osaka, Japan.
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Imanishi
authors.affiliation: Department of Internal Medicine, Division of Endocrinology and Metabolism, Hyogo College of Medicine, Nishinomiya, Japan.
authors.forename: Hidenori
authors.initials: H
authors.lastname: Koyama
authors.affiliation: Department of Metabolism, Endocrinology and Molecular Medicine, Osaka City University Graduate School of Medicine, Osaka, Japan.
authors.forename: Eiji
authors.initials: E
authors.lastname: Ishimura
authors.affiliation: Department of Metabolism, Endocrinology and Molecular Medicine, Osaka City University Graduate School of Medicine, Osaka, Japan.
authors.forename: Masaaki
authors.initials: M
authors.lastname: Inaba
mesh_terms: D000813:Anilides / Q000494:pharmacology; D000818:Animals; D045744:Cell Line, Tumor; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D015870:Gene Expression; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007333:Insulin Resistance; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008687:Metformin / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D047495:PPAR gamma / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D000077205:Pioglitazone; D012333:RNA, Messenger / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000494:pharmacology*; D060749:alpha-2-HS-Glycoprotein / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics
chemical_list: C457499:2-chloro-5-nitrobenzanilide; C556357:Ahsg protein, mouse; D000813:Anilides; D007004:Hypoglycemic Agents; D047495:PPAR gamma; D012333:RNA, Messenger; D045162:Thiazolidinediones; D060749:alpha-2-HS-Glycoprotein; D000077154:Rosiglitazone; D008687:Metformin; D000077205:Pioglitazone