Adiponectin – a key adipokine in the metabolic syndrome

Abstract

Adiponectin is a recently described adipokine that has been recognized as a key regulator of insulin sensitivity and tissue inflammation. It is produced by adipose tissue (white and brown) and circulates in the blood at very high concentrations. It has direct actions in liver, skeletal muscle and the vasculature, with prominent roles to improve hepatic insulin sensitivity, increase fuel oxidation [via up-regulation of adenosine monophosphateactivated protein kinase (AMPK) activity] and decrease vascular inflammation. Adiponectin exists in the circulation as varying molecular weight forms, produced by multimerization. Recent data indicate that the highmolecular weight (HMW) complexes have the predominant action in the liver. In contrast to other adipokines, adiponectin secretion and circulating levels are inversely proportional to body fat content. Levels are further reduced in subjects with diabetes and coronary artery disease. Adiponectin antagonizes many effects of tumour necrosis factor-a (TNF-a) and this, in turn, suppresses adiponectin production. Furthermore, adiponectin secretion from adipocytes is enhanced by thiazolidinediones (which also act to antagonize TNF-a effects). Thus, adiponectin may be the common mechanism by which TNF-a promotes, and the thiazolidinediones suppress, insulin resistance and inflammation. Two adiponectin receptors, termed AdipoR1 and AdipoR2, have been identified and these are ubiquitously expressed. AdipoR1 is most highly expressed in skeletal muscle and has a prominent action to activate AMPK, and hence promote lipid oxidation. AdipoR2 is most highly expressed in liver, where it enhances insulin sensitivity and reduces steatosis via activation of AMPK and increased peroxisome-proliferator-activated receptor a ligand activity. T-cadherin, which is expressed in endothelium and smooth muscle, has been identified as an adiponectin-binding protein with preference for HMW adiponectin multimers. Given the low levels of adiponectin in subjects with the metabolic syndrome, and the beneficial effect of the adipokine in animal studies, there is exciting potential for adiponectin replacement therapy in insulin resistance and related disorders.

Obesity and related consequences to ageing

“…Adiponectin not only diminishes liver free fatty acid influx but also prompts a decrease in circulating free fatty acids by increasing fatty acid oxidation in skeletal muscle and the stimulation of glucose uptake by adipocytes (Li et al 2014). In healthy subjects with normal body weight, circulating adiponectin levels have a cyclic rhythm with a decline of up to 30 % during the night (Whitehead et al 2006). In humans, high levels of circulating adiponectin have been associated with a reduced risk of cardiovascular disease (Zoccali et al 2002).…”

“…Plasma adiponectin levels, examined in humans, were not only decreased in obese and diabetic subjects but were also inversely associated with measures of insulin resistance (Gulcelik et al 2013). Obese subjects lost diurnal variations in adiponectin (Whitehead et al 2006); however, plasma adiponectin levels increase following weight loss (Kern et al 2003) and restore its daily rhythms (Whitehead et al 2006).…”

Zinc-α2-glycoprotein: an adipokine modulator of body fat mass?

“…65 There is evidence that adiponectin acts through activation of AMP kinase to stimulate glucose uptake and fatty acid oxidation in skeletal muscle, and decreases vascular inflammation. 66 The parallel expression pattern for the two adipokines together with the similar regulation by rosiglitazone and TNFa 14 may suggest that ZAG could act similarly to adiponectin in protecting against the obese state.…”

Hypoadiponectinemia in Obesity: Association with Insulin Resistance

“…Moreover, a growing body of evidence suggests that hypoadiponectinemia may play a significant role in the development of Metabolic Syndrome [3]. However, little is known about the significance of circulating adiponectin as a surrogate marker for obesity itself and development of obesity related phenotypes in general population.…”