Adiponectin: ceramidase activity and stress control of the endoplasmic reticle in obesity

Adiponectin is a cytokine synthesized by adipocytes, which acts through receptors (AdipoR1, AdipoR2) and T-cadherin. Recently, it has been identified an endosomal protein, APPL1, that binds to AdipoRs to mediate signaling and nuclear factors of adiponectin. The expression of these receptors depends on the activation phenotype of the macrophages: classical activation (M1) suppresses the expression, and alternative activation (M2) maintains the expression of AdipoRs. Adiponectin regulates the metabolism of carbohydrates and lipids and reducing the production of hepatic glucose and the oxidation of fatty acids; it is also considered a biomarker of endothelial function due to its correlation with endothelial alterations, dyslipidemia, and atherosclerosis. There is a new protective function of Adiponectin against metabolic disorders and organic damage through T- cadherin that facilitates the exosomic release of inadequately folded proteins, controls cellular stress, decreases ceramide levels, and maintains cellular homeostasis. Another essential function of adiponectin is to protect cells from apoptosis induced by endoplasmic reticulum stress and the reduction of the inflammation in adipocytes, hepatocytes, endothelial cells, and pancreatic beta cells as it blocks mitochondrial apoptosis through the activation of the pathway of the protein kinase signal. Adiponectin is a potential biochemical biomarker and an anti-inflammatory in metabolic disorders since it modulates the pathogenesis of overweight and diabetes mellitus type 2, thus considered key to the prognosis and therapeutic intervention of these pathologies.