Elevated circulating
leptin levels have been associated with an increased cardiovascular risk in humans. However, recent meta-analyses show that certain epidemiological studies did not find this association, suggesting distinct effects of
leptin depending on the pathophysiological context. Studies performed in mice deficient in
leptin or in
leptin receptors are often contradictory, showing both protective and deleterious effects of
leptin. These effects appear to vary depending on the genetic background of the animal and the doses of
leptin administered, making interpretation of the results difficult. In humans, elevated adiponectinemia is associated with a favourable cardiovascular risk profile.
Adiponectin exerts protective effects at all stages of development of
atherosclerotic plaque. However, our knowledge of the pathophysiological mechanisms involved in these protective effects has been established from cellular models, which do not necessarily reproduce the pathology in all its complexity. In addition, mouse models have a very different
lipoprotein metabolism from humans, which does not always allow extrapolation of results to humans. Finally, epidemiological studies evaluating
adiponectin as a marker of cardiovascular risk show paradoxical results since a high serum
adiponectin concentration has not been associated with a reduction in the number of cardiovascular events but with an increase of cardiovascular and all causes mortality in healthy subjects and coronary patients. These observations illustrate the paradox of
adipokines actions and show the complexity to use these
biomarkers in
cardiovascular diseases. Resistance to the action of these
adipokines is one of the hypotheses put forward to explain these discrepancies.