Cardiovascular actions of adiponectin: pathophysiologic implications.

The classical view of adipose tissue as a passive reservoir for energy storage is no longer valid. In the past decade, adipose tissue has been shown to have endocrine functions regulating cardiovascular physiology. In the present review we will analyze current knowledge about adiponectin, the most abundant peptide secreted by adipocytes, with particular focus on its cardiovascular actions. Adiponectin secretion is inhibited by TNF-alpha and by catecholamines, and is stimulated by PPAR gamma activation. Adiponectin acts through two main receptors, AdipoR1 and AdipoR2. In the liver, adiponectin modulates lipid and energy metabolism, stimulating fatty acid catabolism and reducing gluconeogenesis. In skeletal muscle, it promotes fatty acid oxidation and glucose uptake. Taken together, the metabolic actions of adiponectin enhance insulin sensitivity and reduce circulating lipid levels. Adiponectin also has a protective effect against atherogenesis, acting on the endothelium and smooth muscle cells, raising NO secretion and inhibiting production of adhesion factors. In the heart, adiponectin inhibits cardiomyocyte hypertrophy and myocardial fibrosis, through poorly understood mechanisms. Adiponectin production has also been shown to be reduced in patients with obesity and type 2 diabetes, and its circulating levels have prognostic significance in various cardiovascular diseases. Finally, the role of this peptide as a therapeutic target has been evaluated, through various lifestyle and pharmacological interventions. Weight loss, physical exercise, renin-angiotensin system inhibitors and PPAR alpha and PPAR gamma agonists enhance adiponectin production. Further studies are needed, however, to clarify the clinical relevance of adiponectin in the pathophysiology and treatment of cardiovascular diseases.