Therapeutic perspectives for adiponectin: an update.

In obesity, the expansion of dysfunctional adipose tissue leads to augmented production of pro-inflammatory adipokines that mediate metabolic changes through their paracrine and/or endocrine actions. By contrast, the secretion and plasma concentration of adiponectin, an adipokine with cardiovascular protective, anti-diabetic and anti-inflammatory properties, are markedly decreased in obesity and its related pathologies. Epidemiological studies on different ethnic groups have identified hypoadiponectinemia as an independent risk factor for type 2 diabetes, hypertension, coronary heart disease and several types of cancers. In animals, replenishment of recombinant adiponectin or transgenic expression of adiponectin can reverse these obesity-related pathological conditions. Although there is currently no direct clinical evidence demonstrating that adiponectin is effective in treating obesity-related cardiometabolic diseases, therapeutic benefits of several anti-diabetic and cardiovascular drugs, such as the agonists of peroxisome proliferator-activated receptor (PPAR) γ and PPAR α and statins, are associated with increased plasma adiponectin in humans. In addition, a number of medicinal herbs and natural compounds with beneficial effects on cardiometabolic diseases, have been shown to increase adiponectin secretion in adipocytes. This review highlights recent advances on multiple beneficial effects of adiponectin and discusses the potential therapeutic interventions for obesity-related cardiometabolic syndromes by targeting adiponectin.

Cross-talk between adipose tissue and vasculature: role of adiponectin.

Adipose tissue is a highly dynamic endocrine organ, secreting a number of bioactive substances (adipokines) regulating insulin sensitivity, energy metabolism and vascular homeostasis. Dysfunctional adipose tissue is a key mediator that links obesity with insulin resistance, hypertension and cardiovascular disease. Obese adipose tissue is characterized by adipocyte hypertrophy and infiltration of inflammatory macrophages and lymphocytes, leading to the augmented production of pro-inflammatory adipokines and vasoconstrictors that induce endothelial dysfunction and vascular inflammation through their paracrine and endocrine actions. By contrast, the secretion of adiponectin, an adipokine with insulin sensitizing and anti-inflammatory activities, is decreased in obesity and its related pathologies. Emerging evidence suggests that adiponectin is protective against vascular dysfunction induced by obesity and diabetes, through its multiple favourable effects on glucose and lipid metabolism as well as on vascular function. Adiponectin improves insulin sensitivity and metabolic profiles, thus reducing the classical risk factors for cardiovascular disease. Furthermore, adiponectin protects the vasculature through its pleiotropic actions on endothelial cells, endothelial progenitor cells, smooth muscle cells and macrophages. Data from both animal and human investigations demonstrate that adiponectin is an important component of the adipo-vascular axis that mediates the cross-talk between adipose tissue and vasculature. This review highlights recent work on the vascular protective activities of adiponectin and discusses the molecular pathways underlying the vascular actions of this adipokine.