Adiponectin regulation in cardiovascular disease: is diseased fat showing its true color?

A dipose tissue can release a plethora of factors termed adipokines. The large family of adipokines includes chemokines, cytokines, lipid factors, and growth factors. Adiponectin, the first cloned protein hormone from adipose tissue, is a metabolically active and anti-inflammatory adipo-kine. Adiponectin mainly circulates in different oligomeric isoforms, including high molecular weight adiponectin, that exerts different biological effects. 1 Expression of adiponec-tin is suppressed by proinflammatory factors, reactive oxygen species, and hypoxia, whereas peroxisome proliferator activated receptor γ agonists stimulate the production of adiponectin in adipocytes. Adiponectin can improve insulin sensitivity, dampen inflammatory responses in macro-phages, and induce the polarization of M2 macrophages. 2 Adiponectin is negatively associated with obesity and insulin resistance, both well-established comorbidities in cardio-vascular disease (CVD). 3 The role of adiponectin in CVD itself is debatable because high levels of adiponectin have been associated with decreased CVD risk in asymptomatic individuals, whereas it can also predict poor prognosis in patients with established CVD. From an historical perspective, adipose tissue was regarded as mere energy storage facilities. However, it is now appreciated that adipose tissue is an active tissue type, with important metabolic and endocrine functions. Classically, 2 types of adi-pose tissue have been identified, white and brown adipose tissue. White adipose tissue is mainly responsible for the release of adipokines, whereas the main function of brown adipose tissue is to generate heat. Brown adipose tissue is prominent in newborns and hibernating mammals 5 and rapidly declines with age. Only recently, evidence was provided that active brown adipose tissue exists in adults. It is mainly found in the subclavicular and neck area, but also small brown fat depots located close to the heart have been identified. 6 A key finding has been the discovery of 2 distinct types of brown fat, classical brown fat (derived from embryogenesis) and inducible brown fat (also referred to as beige fat). 7,8 Neuronal control is a key regulator in induction (browning) and activation of brown adipose tissue, but also brain natriuretic peptide (BNP) released from the heart can mediate this process. 9 It was only recently discovered that not only white but also brown adipose tissue expresses adiponectin. 10 In carotid intima–media thickness studies, higher levels of adiponectin were associated with reduced intima–media thickness in healthy subjects. Also, genetic variation within the adiponectin gene promoter is directly associated with carotid intima–media thickness in healthy subjects, 11 suggesting a causal link between adiponectin …