Induction of adipocyte complement-related protein of 30 kilodaltons by PPARγ agonists: A potential mechanism of insulin sensitization

Terry P. Combs, John A. Wagner, Joel Berger, Tom Doebber, Wen Jun Wang, Bei B. Zhang, Michael Tanen, Anders H. Berg, Stephen O'Rahilly, David B. Savage, Krishna Chatterjee, Stuart Weiss, Patrick J. Larson, Keith M. Gottesdiener, Barry J. Gertz, Maureen J. Charron, Philipp E. Scherer, David E. Moller

Research output: Contribution to journalArticle

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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 PPARγ agonists to modulate Acrp30 expression. After chronic treatment of obese-diabetic (db/db) mice with PPARγ agonists (11 d), mean plasma Acrp30 protein levels increased (γ3x). 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 PPARα 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 PPARγ mutations. Thus, induction of adipose tissue Acrp30 expression and consequent increases in circulating Acrp30 levels represents a novel potential mechanism for PPART-mediated enhancement of whole-body insulin sensitivity. Furthermore, Acrp30 is likely to be a biomarker of in vivo PPARγ activation.

Original languageEnglish (US)
Pages (from-to)998-1007
Number of pages10
JournalEndocrinology
Volume143
Issue number3
DOIs
StatePublished - 2002

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Peroxisome Proliferator-Activated Receptors
Adipocytes
Complement System Proteins
Insulin
Insulin Resistance
rosiglitazone
Fats
Adiponectin
Adipose Tissue
Blood Proteins
Metformin
Streptozocin
Type 2 Diabetes Mellitus
Therapeutics
Biomarkers
Placebos
Mutation
Proteins

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

Combs, T. P., Wagner, J. A., Berger, J., Doebber, T., Wang, W. J., Zhang, B. B., ... Moller, D. E. (2002). Induction of adipocyte complement-related protein of 30 kilodaltons by PPARγ agonists: A potential mechanism of insulin sensitization. Endocrinology, 143(3), 998-1007. https://doi.org/10.1210/en.143.3.998

Induction of adipocyte complement-related protein of 30 kilodaltons by PPARγ agonists : A potential mechanism of insulin sensitization. / Combs, Terry P.; Wagner, John A.; Berger, Joel; Doebber, Tom; Wang, Wen Jun; Zhang, Bei B.; Tanen, Michael; Berg, Anders H.; O'Rahilly, Stephen; Savage, David B.; Chatterjee, Krishna; Weiss, Stuart; Larson, Patrick J.; Gottesdiener, Keith M.; Gertz, Barry J.; Charron, Maureen J.; Scherer, Philipp E.; Moller, David E.

In: Endocrinology, Vol. 143, No. 3, 2002, p. 998-1007.

Research output: Contribution to journalArticle

Combs, TP, Wagner, JA, Berger, J, Doebber, T, Wang, WJ, Zhang, BB, Tanen, M, Berg, AH, O'Rahilly, S, Savage, DB, Chatterjee, K, Weiss, S, Larson, PJ, Gottesdiener, KM, Gertz, BJ, Charron, MJ, Scherer, PE & Moller, DE 2002, 'Induction of adipocyte complement-related protein of 30 kilodaltons by PPARγ agonists: A potential mechanism of insulin sensitization', Endocrinology, vol. 143, no. 3, pp. 998-1007. https://doi.org/10.1210/en.143.3.998
Combs, Terry P. ; Wagner, John A. ; Berger, Joel ; Doebber, Tom ; Wang, Wen Jun ; Zhang, Bei B. ; Tanen, Michael ; Berg, Anders H. ; O'Rahilly, Stephen ; Savage, David B. ; Chatterjee, Krishna ; Weiss, Stuart ; Larson, Patrick J. ; Gottesdiener, Keith M. ; Gertz, Barry J. ; Charron, Maureen J. ; Scherer, Philipp E. ; Moller, David E. / Induction of adipocyte complement-related protein of 30 kilodaltons by PPARγ agonists : A potential mechanism of insulin sensitization. In: Endocrinology. 2002 ; Vol. 143, No. 3. pp. 998-1007.
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AU - Doebber, Tom

AU - Wang, Wen Jun

AU - Zhang, Bei B.

AU - Tanen, Michael

AU - Berg, Anders H.

AU - O'Rahilly, Stephen

AU - Savage, David B.

AU - Chatterjee, Krishna

AU - Weiss, Stuart

AU - Larson, Patrick J.

AU - Gottesdiener, Keith M.

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