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Improved fibrinolytic activity during exercise may be an effect of the adipocyte-derived hormones leptin and adiponectin
Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
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2008 (English)In: Thrombosis Research, ISSN 0049-3848, E-ISSN 1879-2472, Vol. 122, no 5, 701-708 p.Article in journal (Refereed) Published
Abstract [en]

Physical activity is associated with improved fibrinolytic activity and reduced risk for cardiovascular disease. High levels of leptin and low levels of adiponectin, both adipocyte-derived hormones, or adipokines, are related to dysfibrinolysis and risk for cardiovascular disease. In this study, we explored if improved fibrinolytic activity during exercise could be linked to changes in leptin and adiponectin levels.

Materials and methods

Twenty healthy men (mean age 36 years) participated in a 14-day long skiing expedition in the Swedish mountains. They were randomly assigned to either a 40% or a 30% fat-based diet. Anthropometry, lipids, fibrinolytic activity (PAI-1 activity, tPA activity and mass) and adipokines (leptin and adiponectin) were measured before, during and six weeks after the expedition.


PAI-1 activity and circulating levels of leptin decreased whereas levels of adiponectin increased during exercise. The fall in PAI-1 activity showed a strong linear association with changes in leptin and adiponectin levels (p = 0.001 and p < 0.001, respectively). Changes in leptin and adiponectin levels were independent of decreasing waist circumference. However, the association between anthropometric measures and adipokines changed considerably during the expedition. Adiponectin was weakly and negatively associated with BMI at baseline. In contrast, there was a strong positive association between adiponectin and BMI after two weeks of exercise, whereas the association between leptin and BMI became less pronounced. In addition, increasing leptin and decreasing adiponectin levels were associated with increasing PAI-1 activity during the six weeks following the expedition. After six weeks of normal activity, fibrinolytic activity and hormone levels returned towards baseline levels.


Heavy exercise induced improved fibrinolytic activity, which was associated independently with changes in circulating levels of the adipocyte-derived hormones leptin and adiponectin. Improved fibrinolytic activity (and reduced risk for cardiovascular disease) related to physical activity could possibly be mediated by leptin and adiponectin.

Place, publisher, year, edition, pages
2008. Vol. 122, no 5, 701-708 p.
Keyword [en]
Fibrinolytic activity; Adipocyte-derived hormones; Leptin; Adiponectin; Healthy men; Physical activity; Clinical experiment; Repeated measures
URN: urn:nbn:se:umu:diva-10470DOI: 10.1016/j.thromres.2008.01.010PubMedID: 18387655OAI: diva2:150141
Available from: 2008-09-15 Created: 2008-09-15 Last updated: 2010-10-11Bibliographically approved
In thesis
1. Adipocyte-derived hormones and cardiovascular disease
Open this publication in new window or tab >>Adipocyte-derived hormones and cardiovascular disease
2010 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Obesity is increasing globally and related to major changes in lifestyle. This increase is associated with an increased risk of cardiovascular disease (CVD). Knowledge about adipose tissue as a metabolic-endocrine organ has increased during the last few decades. Adipose tissue produces a number of proteins with increased body weight, many of which are important for food intake and satiety, insulin sensitivity, and vessel integrity, and aberrations have been related to atherosclerosis. Notably, the risk for developing CVD over the course of a lifetime differs between men and women. In Northern Sweden, men have a higher risk for myocardial infarction (MI). However, the incidence is declining in men but not in women. These sex differences could be due to functional and anatomical differences in the fat mass and its functions.

The primary aim of this thesis was to evaluate associations between the adipocyte-derived hormones leptin and adiponectin, and fibrinolysis and other variables associated with the metabolic syndrome, and particularly whether these associations differ between men and women. Another aim was to evaluate these associations during physical exercise and pharmacological intervention (i.e. enalapril). Finally, whether leptin and adiponectin predict a first MI or sudden cardiac death with putative sex differences was also investigated.

The first study used a cross-sectional design and included 72 men and women  recruited from the WHO MONICA project. We found pronounced sex differences in the associations with fibrinolytic variables. Leptin was associated with fibrinolytic factors in men, whereas insulin resistance was strongly associated with all fibrinolytic factors in women. The second study was an experimental observational study with 20 men exposed to strenuous physical exercise. During exercise, leptin levels decreased and adiponectin levels increased, and both were strongly associated with an improved fibrinolytic capacity measured as decreased PAI-1 activity. Changes in insulin sensitivity were not associated with changing adiponectin levels. The third study was a randomised, double-blind, single centre clinical trial including 46 men and 37 women who had an earlier MI. The study duration was one year, and participating subjects were randomised to either placebo or ACE inhibitor (i.e. enalapril). Circulating leptin levels were not associated with enalapril treatment. During the one-year study, changes in leptin levels were associated with changes in circulating levels of tPA mass, PAI-1 mass, and tPA-PAI complex in men, but not vWF. These associations were found in all men and men on placebo treatment. In women on enalapril treatment there was an association between changes in leptin and changes in vWF. In the fourth study, the impact of leptin, adiponectin, and their ratio on future MI risk or sudden cardiac death was tested in a prospective nested casecontrol study within the framework of the WHO MONICA, Västerbotten Intervention Project (VIP), and Västerbotten  Mammary Screening Program (MSP). A total 564 cases (first-ever MI or sudden cardiac death) and 1082 matched controls were selected. High leptin, low adiponectin, and a high leptin/adiponectin ratio independently predicted a first-ever MI, possibly with higher risk in men in regards to leptin. The association was found for non-fatal cases with ST-elevation MI. Subjects with low adiponectin levels had their MI earlier than those with high levels.

In conclusion, the adipocyte-derived hormones leptin and adiponectin are related to the development of CVD with a sex difference, and fibrinolytic mechanisms could be possible contributors to CVD risk.

Place, publisher, year, edition, pages
Umeå: Umeå universitet, 2010. 110 p.
Umeå University medical dissertations, ISSN 0346-6612 ; 1358
leptin, adiponectin, fibrinolysis, vWF, myocardial infarction, sex differences, physical activity, risk factors
urn:nbn:se:umu:diva-36679 (URN)978-91-7459-041-8 (ISBN)
Public defence
2010-10-29, Tandläkarhögskolan Sal B, Umeå universitet, Umeå, 09:00 (Swedish)
Available from: 2010-10-11 Created: 2010-10-07 Last updated: 2010-10-11Bibliographically approved

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