Food deprivation induces adipose plasminogen activator inhibitor-1 (PAI-1) expression without accumulation of plasma PAI-1 in genetically obese and diabetic db/db mice

Katsutaka Oishi; Naoki Ohkura; Juzo Matsuda; Norio Ishida

doi:10.1160/TH07-04-0268

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2007; 98(04): 864-870
DOI: 10.1160/TH07-04-0268

Animal Models

Schattauer GmbH

Food deprivation induces adipose plasminogen activator inhibitor-1 (PAI-1) expression without accumulation of plasma PAI-1 in genetically obese and diabetic db/db mice

Authors

Katsutaka Oishi

¹Clock Cell Biology Research Group, Institute for Biological Resources and Functions, National Institute of Advanced Industrial Science and Technology (AIST), Higashi, Tsukuba, Ibaraki, Japan
Naoki Ohkura

²Department of Clinical Molecular Biology, Faculty of Pharmaceutical Sciences, Teikyo University, Suarashi, Sagamiko, Sagamihara, Kanagawa, Japan
Juzo Matsuda

²Department of Clinical Molecular Biology, Faculty of Pharmaceutical Sciences, Teikyo University, Suarashi, Sagamiko, Sagamihara, Kanagawa, Japan
Norio Ishida

¹Clock Cell Biology Research Group, Institute for Biological Resources and Functions, National Institute of Advanced Industrial Science and Technology (AIST), Higashi, Tsukuba, Ibaraki, Japan

³Graduate School of Life and Environmental Sciences, University of Tsukuba, Tsukuba, Ibaraki, Japan

Abstract

Summary

Relationships between energy intake and fibrinolytic functions have been documented in detail. We evaluated food deprivation (FD) as a means of modulating fibrinolytic activity in genetically obese and diabetic db/db mice and in their lean counterparts. Twelve hours of FD induced considerable gene expression of plasminogen activator inhibitor-1 (PAI-1) in both epididymal (3.8-fold, p<0.05) and intestinal (2.4-fold, p<0.05) adipose tissues without affecting plasma PAI-1 levels in db/db mice, whereas the FD did not affect these parameters in wild-type mice. Importantly, 24 hours of FD increased the plasma PAI-1 content in wild-type (1.9-fold, p<0.01) but not in db/db mice, although adipose PAI-1 mRNA levels were significantly increased in db/db mice. The plasma PAI-1 content significantly correlated with hepatic PAI-1 mRNA levels in wild-type (r=0.84, p<0.01) and in db/db (r=0.63, p<0.01) mice. However, plasma PAI-1 did not correlate with adipose PAI-1 expression in db/db mice, although adipose tissue in general is thought to be the principal site of PAI-1 production in obesity. Hepatic PAI-1 expression was closely correlated with serum levels of free fatty acids in wild-type (r=0.72, p<0.01), but not in db/db mice. Adipose PAI-1 expression significantly correlated with serum corticosterone levels in both genotypes (wild-type, r=0.52, p<0.05; db/db, r=0.51, p<0.01), suggesting that adipose PAI-1 expression is up-regulated by fastinginduced glucocorticoids. The present findings suggested that fasting differentially affects fibrinolytic activity in obese and lean subjects and that PAI-1 expression in the liver as well as in adipose tissues comprises an important determinant of increased risk for cardiovascular disease in obesity.

Keywords

Plasminogen activator inhibitor-1 - adipose tissue - liver - obesity - food deprivation - db/db mouse

Full Text

References

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