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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

Katsutaka Oishi
1   Clock 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
2   Department of Clinical Molecular Biology, Faculty of Pharmaceutical Sciences, Teikyo University, Suarashi, Sagamiko, Sagamihara, Kanagawa, Japan
,
Juzo Matsuda
2   Department of Clinical Molecular Biology, Faculty of Pharmaceutical Sciences, Teikyo University, Suarashi, Sagamiko, Sagamihara, Kanagawa, Japan
,
Norio Ishida
1   Clock Cell Biology Research Group, Institute for Biological Resources and Functions, National Institute of Advanced Industrial Science and Technology (AIST), Higashi, Tsukuba, Ibaraki, Japan
3   Graduate School of Life and Environmental Sciences, University of Tsukuba, Tsukuba, Ibaraki, Japan
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Further Information

Publication History

Received 13 April 2007

Accepted after resubmission 02 July 2007

Publication Date:
01 December 2017 (online)

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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
 

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