| Adiponectin (a.k.a., GBP-28, apM1, AdipoQ, and Acrp30)
Adipocytes (fat cells) express a variety of proteins that function in the homeostatic control of glucose and lipid metabolism. Insulin regulates the translocation and secretion of many of these proteins in response to changes in energy balance. Adipocyte complement-related protein of 30 kDa (Acrp30) - now known as adiponectin - is a protein whose secretion from adipocytes is enhanced by insulin stimulation.
Adiponectin research will lead to a better understanding of obesity, and obesity-related disorders, which are reaching alarming proportions in the US and are on the increase in Europe and Asia. In particular, it has been suggested that the development of non-insulin dependent (type 2) diabetes may involve dysregulation of adiponectin secretion (1). In support of the link between obesity and type 2 diabetes, it has been shown that decreased expression of adiponectin correlates with insulin resistance (2,3), and that adiponectin appears to be a potent insulin enhancer (4).
Adiponectin is a novel adipose tissue-specific protein that has structural homology to collagen VIII, X, and complement factor C1q, and that circulates in human plasma in high levels. It is one of the physiologically active polypeptides secreted by adipose tissue, whose multiple functions have started to be understood in the last few years. A reduction in adiponectin expression is associated with insulin resistance in some animal models. Further, administration of adiponectin has been accompanied by a reduction in plasma glucose and an increase in insulin sensitivity. In addition, thiazolidinediones, drugs that enhance insulin sensitivity through stimulation of the peroxisome proliferator-activated receptor-g, increase plasma adiponectin and mRNA levels in mice. Plasma adiponectin levels have been reported to be decreased in some insulin-resistant states, such as obesity and type 2 diabetes mellitus, and also in patients with coronary artery disease. On the other hand, chronic renal failure, type 1 diabetes and anorexia nervosa are associated with increased plasma adiponectin levels. Concentrations of plasma adiponectin have been shown to correlate negatively with glucose, insulin, triglyceride levels and body mass index, and positively with HDL-cholesterol levels and insulin-stimulated glucose disposal. Weight loss and therapy with thiazolidinediones increased endogenous adiponectin production in humans. Adiponectin increases insulin sensitivity by increasing tissue fat oxidation resulting in reduced circulating fatty acid levels, and reduced intracellular triglyceride content in liver and muscle (5).
Adiponectin also seems to play a protective role in experimental models of vascular injury. In humans, adiponectin levels are inversely related to the degree of adiposity and positively associated with insulin sensitivity both in healthy subjects and in diabetic patients. This protein also suppresses the expression of adhesion molecules in vascular endothelial cells and cytokine production from macrophages, thus inhibiting the inflammatory processes that occur during the early phases of atherosclerosis. In view of these data, it is possible that hypoadiponectinemia may play a role in the development of atherosclerotic vascular disease.
The ability of adiponectin to increase insulin sensitivity in conjunction with its anti-inflammatory and anti-atherogenic properties have made of this novel adipocytokine a promising therapeutical tool for the future.
1. Nemet, D., et al. (2002) Relationships among adiponectin and other adipose cytokines, body composition, and fasting insulin in lower socioeconomic middle school children. American Physiological Societyys (APS) Abstracts.
2. Yamauchi T., et al. (2001) The fat-derived hormone adiponectin reverses insulin resistance associated with both lipoatrophy and obesity. Nature Medicine, Aug;7(8):941-6.
3. Kubota, N., et al. (2002) Disruption of adiponectin causes insulin resistance and neointimal formation. J Biol Chem. May 24 (epub ahead of print).
4. Berg A.H., et al. (2001) The adipocyte-secreted protein Acrp30 enhances hepatic insulin action. Nature Medicine, Aug;7(8):947-53.
5. European Journal of Endocrinology (2003) 148 293-300
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