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Plasminogen activator inhibitor-1 modulates adipocyte differentiation.
Am J Physiol Endocrinol Metab. 2006 Jan; 290(1):E103-E113.AJ

Abstract

Increased plasminogen activator inhibitor-1 (PAI-1) is linked to obesity and insulin resistance. However, the functional role of PAI-1 in adipocytes is unknown. This study was designed to investigate effects and underlying mechanisms of PAI-1 on glucose uptake in adipocytes and on adipocyte differentiation. Using primary cultured adipocytes from PAI-1(+/+) and PAI-1(-/-) mice, we found that PAI-1 deficiency promoted adipocyte differentiation, enhanced basal and insulin-stimulated glucose uptake, and protected against tumor necrosis factor-alpha-induced adipocyte dedifferentiation and insulin resistance. These beneficial effects were associated with upregulated glucose transporter 4 at basal and insulin-stimulated states and upregulated peroxisome proliferator-activated receptor-gamma (PPARgamma) and adiponectin along with downregulated resistin mRNA in differentiated PAI-1(-/-) vs. PAI-1(+/+) adipocytes. Similarly, inhibition of PAI-1 with a neutralizing anti-PAI-1 antibody in differentiated 3T3-L1 adipocytes further promoted adipocyte differentiation and glucose uptake, which was associated with increased expression of transcription factors PPARgamma, CCAAT enhancer-binding protein-alpha (C/EBPalpha), and the adipocyte-selective fatty acid-binding protein aP2, thus mimicking the phenotype in PAI-1(-/-) primary adipocytes. Conversely, overexpression of PAI-1 by adenovirus-mediated gene transfer in 3T3-L1 adipocytes inhibited differentiation and reduced PPARgamma, C/EBPalpha, and aP2 expression. This was also associated with a decrease in urokinase-type plasminogen activator mRNA expression, decreased plasmin activity, and increased collagen I mRNA expression. Collectively, these results indicate that absence or inhibition of PAI-1 in adipocytes protects against insulin resistance by promoting glucose uptake and adipocyte differentiation via increased PPARgamma expression. We postulate that these PAI-1 effects on adipocytes may, at least in part, be mediated via modulation of plasmin activity and extracellular matrix components.

Authors+Show Affiliations

Liang X
Department of Pathology, Vanderbilt University School of Medicine, Nashville, TN 37232-2561, USA.
Kanjanabuch T
No affiliation info available
Mao SL
No affiliation info available
Hao CM
No affiliation info available
Tang YW
No affiliation info available
Declerck PJ
No affiliation info available
Hasty AH
No affiliation info available
Wasserman DH
No affiliation info available
Fogo AB
No affiliation info available
Ma LJ
No affiliation info available

MeSH

3T3-L1 CellsAdipocytesAdiponectinAnimalsAntibodies, MonoclonalCCAAT-Enhancer-Binding Protein-alphaCell DifferentiationCollagen Type IFatty Acid-Binding ProteinsFibrinolysinGene ExpressionGlucoseGlucose Transporter Type 4InsulinMaleMiceMice, Inbred C57BLMice, KnockoutPPAR gammaPlasminogen Activator Inhibitor 1RNA, MessengerResistinTumor Necrosis Factor-alphaUrokinase-Type Plasminogen Activator

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16144810

Citation

Liang, Xiubin, et al. "Plasminogen Activator Inhibitor-1 Modulates Adipocyte Differentiation." American Journal of Physiology. Endocrinology and Metabolism, vol. 290, no. 1, 2006, pp. E103-E113.
Liang X, Kanjanabuch T, Mao SL, et al. Plasminogen activator inhibitor-1 modulates adipocyte differentiation. Am J Physiol Endocrinol Metab. 2006;290(1):E103-E113.
Liang, X., Kanjanabuch, T., Mao, S. L., Hao, C. M., Tang, Y. W., Declerck, P. J., Hasty, A. H., Wasserman, D. H., Fogo, A. B., & Ma, L. J. (2006). Plasminogen activator inhibitor-1 modulates adipocyte differentiation. American Journal of Physiology. Endocrinology and Metabolism, 290(1), E103-E113.
Liang X, et al. Plasminogen Activator Inhibitor-1 Modulates Adipocyte Differentiation. Am J Physiol Endocrinol Metab. 2006;290(1):E103-E113. PubMed PMID: 16144810.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Plasminogen activator inhibitor-1 modulates adipocyte differentiation. AU - Liang,Xiubin, AU - Kanjanabuch,Talerngsak, AU - Mao,Su-Li, AU - Hao,Chuan-Ming, AU - Tang,Yi-Wei, AU - Declerck,Paul J, AU - Hasty,Alyssa H, AU - Wasserman,David H, AU - Fogo,Agnes B, AU - Ma,Li-Jun, Y1 - 2005/09/06/ PY - 2005/9/8/pubmed PY - 2006/2/28/medline PY - 2005/9/8/entrez SP - E103 EP - E113 JF - American journal of physiology. Endocrinology and metabolism JO - Am J Physiol Endocrinol Metab VL - 290 IS - 1 N2 - Increased plasminogen activator inhibitor-1 (PAI-1) is linked to obesity and insulin resistance. However, the functional role of PAI-1 in adipocytes is unknown. This study was designed to investigate effects and underlying mechanisms of PAI-1 on glucose uptake in adipocytes and on adipocyte differentiation. Using primary cultured adipocytes from PAI-1(+/+) and PAI-1(-/-) mice, we found that PAI-1 deficiency promoted adipocyte differentiation, enhanced basal and insulin-stimulated glucose uptake, and protected against tumor necrosis factor-alpha-induced adipocyte dedifferentiation and insulin resistance. These beneficial effects were associated with upregulated glucose transporter 4 at basal and insulin-stimulated states and upregulated peroxisome proliferator-activated receptor-gamma (PPARgamma) and adiponectin along with downregulated resistin mRNA in differentiated PAI-1(-/-) vs. PAI-1(+/+) adipocytes. Similarly, inhibition of PAI-1 with a neutralizing anti-PAI-1 antibody in differentiated 3T3-L1 adipocytes further promoted adipocyte differentiation and glucose uptake, which was associated with increased expression of transcription factors PPARgamma, CCAAT enhancer-binding protein-alpha (C/EBPalpha), and the adipocyte-selective fatty acid-binding protein aP2, thus mimicking the phenotype in PAI-1(-/-) primary adipocytes. Conversely, overexpression of PAI-1 by adenovirus-mediated gene transfer in 3T3-L1 adipocytes inhibited differentiation and reduced PPARgamma, C/EBPalpha, and aP2 expression. This was also associated with a decrease in urokinase-type plasminogen activator mRNA expression, decreased plasmin activity, and increased collagen I mRNA expression. Collectively, these results indicate that absence or inhibition of PAI-1 in adipocytes protects against insulin resistance by promoting glucose uptake and adipocyte differentiation via increased PPARgamma expression. We postulate that these PAI-1 effects on adipocytes may, at least in part, be mediated via modulation of plasmin activity and extracellular matrix components. SN - 0193-1849 UR - https://www.unboundmedicine.com/medline/citation/16144810/Plasminogen_activator_inhibitor_1_modulates_adipocyte_differentiation_ DB - PRIME DP - Unbound Medicine ER -