Adiponectin

Adiponectin is the most abundant peptide hormone secreted by adipocytes.^1-3 Other cell types such as skeletal and cardiac myocytes and endothelial cells can produce lesser amounts of this protein. Adiponectin has a short half-life of 45-75 minutes despite its minimal degradation during circulation. Its clearance is predominantly by the liver but can also bind pancreatic beta cells and certain heart and kidney cell types.¹ Adiponectin participates in glucose regulation but also exerts anti-inflammatory, anti-atherogenic and cardioprotective effects as well as effects on lipid metabolism and fatty acid oxidation.^1,4 Adiponectin directly acts on the liver, skeletal muscle, and vasculature through insulin sensitization and anti-inflammatory/anti-atherogenic effects.¹ Adiponectin increases insulin secretion from the pancreas and mediates insulin sensitivity in skeletal muscle.^1,3,5 Adiponectin enhances basal glucose and insulin-stimulated glucose uptake in adipose tissues.^1,3,4 Adiponectin increases insulin sensitivity and down-regulates gluconeogenesis in the liver while activating fatty acid oxidation.^1,3 Studies have shown that adiponectin decreases inflammation in macrophages, endothelial tissue, muscle, and epithelial cells.³ There is evidence that adiponectin prevents the production of reactive oxidative species and promotes down-regulation of inflammation.³ Moreover, it has been shown to inhibit CRP secretion and suppression of pathways involving NF-kB signaling and TNF-Alpha.³

Obese patients tend to have decreased serum levels of adiponectin. Various cross-sectional studies have established an inverse relationship between adiponectin serum levels and BMI and fat mass.^6-8 Adiponectin levels are increased in extremely lean patients suffering from conditions such as anorexia nervosa.⁷ Weight loss through means such as diet and exercise and bariatric surgery have resulted in increased plasma levels of adiponectin in patients.⁷ Diminished serum adiponectin levels is a feature in pathologies such as gestational diabetes.^7,9 Strong genetic associations between adiponectin levels and insulin resistance have also been established⁵ and low levels of it predict future onset of insulin resistance.^7,10 Adiponectin levels demonstrate an inverse correlation with adiposity and proinflammatory cytokines in patients suffering from metabolic syndrome.^11-14 Low levels of adiponectin predict a higher incidence of adverse cardiovascular events such as myocardial infarctions and atherosclerosis.^14,15

Recently, adiponectin has shown to exhibit activity in functions of cell proliferation, where it has been shown to counter cell growth and induce apoptosis.¹⁴ It is also noteworthy, however, that several recent studies have also demonstrated adiponectin to have anti apoptotic and proliferative roles.¹⁴ Accumulating evidence suggest that adiponectin is implicated in the pathogenesis of several malignancies.^13,16,17 Several observational studies showed that low adiponectin levels are associated with higher risk for breast, cervical, endometrial, ovarian and prostate cancer.^13,16,17 A relationship between adiponectin and the aggressiveness of some of these tumors has also been reported.^13,16-18