CLOCK is involved in obesity‐induced disordered fibrinolysis in ob/ob mice by regulating PAI‐1 gene expression

Background: An increased level of obesity‐induced plasma plasminogen activator inhibitor‐1 (PAI‐1) is considered a risk factor for cardiovascular disease. Aim: The present study investigates whether the circadian clock component CLOCK is involved in obesity‐induced PAI‐1 elevation. Methods: We exami...

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Bibliographic Details
Published in:Journal of thrombosis and haemostasis 2006-08, Vol.4 (8), p.1774-1780
Main Authors: OISHI, K., OHKURA, N., WAKABAYASHI, M., SHIRAI, H., SATO, K., MATSUDA, J., ATSUMI, G., ISHIDA, N.
Format: Article
Language:English
Subjects:
adipose tissue
Adipose Tissue - metabolism
Animals
circadian clock
Circadian Rhythm
Clock mutant mouse
CLOCK Proteins
Fibrinolysis
Gene Expression Regulation
Heterozygote
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Mice, Mutant Strains
Mice, Obese
ob/ob mouse
obesity
Obesity - genetics
Plasminogen Activator Inhibitor 1 - biosynthesis
plasminogen activator inhibitor‐1
Time Factors
Trans-Activators - metabolism
Trans-Activators - physiology
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Summary:Background: An increased level of obesity‐induced plasma plasminogen activator inhibitor‐1 (PAI‐1) is considered a risk factor for cardiovascular disease. Aim: The present study investigates whether the circadian clock component CLOCK is involved in obesity‐induced PAI‐1 elevation. Methods: We examined plasma PAI‐1 and mRNA expression levels in tissues from leptin‐deficient obese and diabetic ob/ob mice lacking functional CLOCK protein. Results: Our results demonstrated that plasma PAI‐1 levels were augmented in a circadian manner in accordance with the mRNA expression levels in ob/ob mice. Surprisingly, a Clock mutation normalized the plasma PAI‐1 concentrations in accordance with the mRNA levels in the heart, lung and liver of ob/ob mice, but significantly increased PAI‐1 mRNA levels in adipose tissue by inducing adipocyte hypertrophy in ob/ob mice. The Clock mutation also normalized tissue PAI‐1 antigen levels in the liver but not in the adipose tissue of ob/ob mice. Conclusion: These observations suggest that CLOCK is involved in obesity‐induced disordered fibrinolysis by regulating PAI‐1 gene expression in a tissue‐dependent manner. Furthermore, it appears that obesity‐induced PAI‐1 production in adipose tissue is not closely related to systemic PAI‐1 increases in vivo.
ISSN:1538-7933
1538-7836
DOI:10.1111/j.1538-7836.2006.02032.x