title: Induction of adipocyte complement-related protein of 30 kilodaltons by PPARgamma agonists: a potential mechanism of insulin sensitization.
abstract: Adipocyte complement-related protein of 30 kDa (Acrp30, adiponectin, or AdipoQ) is a fat-derived secreted protein that circulates in plasma. Adipose tissue expression of Acrp30 is lower in insulin-resistant states and it is implicated in the regulation of in vivo insulin sensitivity. Here we have characterized the ability of PPARgamma agonists to modulate Acrp30 expression. After chronic treatment of obese-diabetic (db/db) mice with PPARgamma agonists (11 d), mean plasma Acrp30 protein levels increased (>3x). Similar effects were noted in a nongenetic type 2 diabetes model (fat-fed and low-dose streptozotocin-treated mice). In contrast, treatment of mice (db/db or fat-fed) with metformin or a PPARalpha agonist did not affect plasma Acrp30 protein levels. In a cohort of normal human subjects, 14-d treatment with rosiglitazone also produced a 130% increase in circulating Acrp30 levels vs. placebo. In addition, circulating Acrp30 levels were suppressed 5-fold in patients with severe insulin resistance in association with dominant-negative PPARgamma mutations. Thus, induction of adipose tissue Acrp30 expression and consequent increases in circulating Acrp30 levels represents a novel potential mechanism for PPARgamma-mediated enhancement of whole-body insulin sensitivity. Furthermore, Acrp30 is likely to be a biomarker of in vivo PPARgamma activation.
authors.affiliation: Department of Cell Biology, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
authors.forename: Terry P
authors.initials: TP
authors.lastname: Combs
authors.forename: John A
authors.initials: JA
authors.lastname: Wagner
authors.forename: Joel
authors.initials: J
authors.lastname: Berger
authors.forename: Tom
authors.initials: T
authors.lastname: Doebber
authors.forename: Wen-Jun
authors.initials: WJ
authors.lastname: Wang
authors.forename: Bei B
authors.initials: BB
authors.lastname: Zhang
authors.forename: Michael
authors.initials: M
authors.lastname: Tanen
authors.forename: Anders H
authors.initials: AH
authors.lastname: Berg
authors.forename: Stephen
authors.initials: S
authors.lastname: O'Rahilly
authors.forename: David B
authors.initials: DB
authors.lastname: Savage
authors.forename: Krishna
authors.initials: K
authors.lastname: Chatterjee
authors.forename: Stuart
authors.initials: S
authors.lastname: Weiss
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Larson
authors.forename: Keith M
authors.initials: KM
authors.lastname: Gottesdiener
authors.forename: Barry J
authors.initials: BJ
authors.lastname: Gertz
authors.forename: Maureen J
authors.initials: MJ
authors.lastname: Charron
authors.forename: Philipp E
authors.initials: PE
authors.lastname: Scherer
authors.forename: David E
authors.initials: DE
authors.lastname: Moller
mesh_terms: D016475:3T3 Cells; D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism*; D052242:Adiponectin; D000818:Animals; D001798:Blood Proteins / Q000096:biosynthesis*; D018592:Cross-Over Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007328:Insulin / Q000494:pharmacology*; D007333:Insulin Resistance; D036341:Intercellular Signaling Peptides and Proteins; D008297:Male; D008687:Metformin / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D010865:Pilot Projects; D011506:Proteins; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists* / Q000235:genetics; D000077154:Rosiglitazone; D013844:Thiazoles / Q000494:pharmacology; D045162:Thiazolidinediones; D014157:Transcription Factors / Q000819:agonists* / Q000235:genetics
chemical_list: D052242:Adiponectin; D001798:Blood Proteins; D007004:Hypoglycemic Agents; D007328:Insulin; D036341:Intercellular Signaling Peptides and Proteins; D011506:Proteins; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D013844:Thiazoles; D045162:Thiazolidinediones; D014157:Transcription Factors; D000077154:Rosiglitazone; D008687:Metformin