Adiponectin, the missing link in insulin resistance and obesity

Abstract

Obesity and insulin resistance have been recognised as leading causes of major health issues, particularly diabetes type 2 and metabolic syndrome. Although obesity, defined as excess body fat, is frequently accompanied by insulin resistance, diabetes, metabolic syndrome and cardiovascular diseases, the molecular basis for the link between obesity and those diseases has not yet been clarified. Adipose tissue expresses various secretory proteins, including leptin, tumour necrosis factor-alpha and adiponectin, which may be involved in the regulation of energy expenditure, lipid metabolism and insulin resistance. The aim of this study is to provide an overview of the metabolic alterations occurring in insulin resistance as well as to review the biological roles of adiponectin, particularly in the regulation of fatty acid oxidation and insulin action. Adiponectin is the most abundant gene product in adipose tissue and accounts for 0.01% of total plasma protein. Plasma adiponectin level is decreased in obesity, both in children and adults, and it is negatively associated to plasma insulin and positively associated to plasma triglycerides. Low levels of adiponectin decreases fatty acid oxidation in muscle. Recent data have demonstrated that adiponectin effects are mediated by the interaction with muscle and hepatic receptors through activation of AMP kinase, the cellular "fuel gauge", which in turn inhibits acetyl CoA carboxylase and increases fatty acid beta-oxidation. Since there is no available recombinant adiponectin for human use, its direct effects on human metabolism remain unknown, but this hormone appears to be promising in the treatment of obesity an related metabolic disorders.