Adiponectin: an update.
The discoveries of leptin and adiponectin were breakthroughs in the field of metabolic diseases. Adipose cells produce both proteins and release them into the circulation. Leptin acts as a fundamental signal for the brain to modulate food intake as a function of energy status. Loss of leptin function results in obesity. Although a biological role for adiponectin has not been firmly established, clinical and experimental observations indicate that low plasma levels contribute to the pathogenesis of insulin resistance, type 2 diabetes and cardiovascular diseases in obese or overweight patients. Adiponectin circulates as several multimeric species, including a high-molecular-weight form thought to be the most clinically relevant. Adiponectin exerts anti-atherogenic effects by targeting vascular endothelial cells and macrophages and insulin-sensitizing effects, mainly predominantly in muscle and liver. The best-characterized molecular mechanism mediating adiponectin's metabolic and vascular activities involved stimulation of AMP kinase activity. Adiponectin signaling pathways comprise at least two putative receptors (AdipoR1 and AdipoR2). Ways to enhance adiponectin bioactivity are actively being sought. In obesity, reducing chronic adipose-tissue inflammation and macrophage infiltration into it could be beneficial to reverse downregulation of adiponectin gene expression by pro-inflammatory cytokines. Pharmacologically, thiazolidinediones and cannabinoid-1 receptor blockers (e.g., rimonabant) increase plasma adiponectin and gene expression in adipocytes. Finally, AdipoR activation to mimic adiponectin actions could prove beneficial to reduce metabolic risk factors in conditions, such as obesity, where low adiponectinemia prevails.
Guerre-Millo
M
M
Service de nutrition, Inserm U872, hôpital Hôtel-Dieu, 1, place du Parvis-de-Notre-Dame, 75181 Paris cedex 04, France. mguerre@bhdc.jussieu.fr
D000263:Adenylate Kinase / Q000378:metabolism; D052242:Adiponectin / Q000502:physiology*; D004789:Enzyme Activation; D006801:Humans; D008099:Liver / Q000502:physiology; D018482:Muscle, Skeletal / Q000502:physiology; D054419:Receptors, Adiponectin / Q000235:genetics / Q000502:physiology
D052242:Adiponectin; D054419:Receptors, Adiponectin; D000263:Adenylate Kinase