Adipocytokines: The pied pipers

Abstract

Even though there have been major advances in therapy, atherosclerosis and coronary artery disease retain their lead as one of the major causes of morbidity and mortality in the first decade of 21st century. To add to the woes, we have diabetes, obesity and insulin resistance as the other causes. The adipose tissue secretes several bioactive mediators that influence inflammation, insulin resistance, diabetes, atherosclerosis and several other pathologic states besides the regulation of body weight. These mediators are mostly proteins and are termed “adipocytokines”. Adiponectin, resistin, visfatin, retinol binding protein-4 (RBP-4) and leptin are a few such proteins. Adiponectin is a multimeric protein, acting via its identified receptors, AdipoR1 and AdipoR2. It is a potential biomarker for metabolic syndrome and has several antiinflammatory actions. Adiponectin increases insulin sensitivity and ameliorates obesity. Resistin, another protein secreted by the adipose tissue, derived its name due to its involvement in the development of insulin resistance. It plays a role in the pathophysiology of several conditions because of its robust proinflammatory activity mediated through the activation of extracellular signal regulated kinases 1 and 2 (ERK 1/2). In 2007, resistin was reported to have protective effect in ischemia-reperfusion injury and myocyte-apoptosis in the setting of myocardial infarction (MI). RBP-4 is involved in the developmental pathology of type 2 diabetes mellitus and obesity. Visfatin has been described as an inflammatory cytokine. Increased expression of visfatin mRNA has been observed in inflammatory conditions like atherosclerosis and inflammatory bowel disease. Leptin mainly regulates the food intake and energy homeostasis. Leptin resistance has been associated with development of obesity and insulin resistance. Few drugs (thiazolidinediones, rimonabant, statins, etc.) and some lifestyle modifications have been found to improve the levels of adipocytokines. Their role in therapy has a lot in store to be explored upon.

Impaired Glucose Tolerance, Obesity and Inflammatory Mediators

“…It has been recognized that elevation of CRP concentrations is an independent predictive parameter of T2DM, which is also associated with various components of the metabolic syndrome such as obesity, IR, and dyslipidemia [20][21][22][23][24]. A number of previous study have reported that high sensitivity (hs) CRP is also related to circulating IL-6 levels [24,32,33] and IL-6 is a powerful inducer of CRP production in the liver [18]. In addition, abdominal obesity is associated with elevated plasma hs-CRP concentration and it has shown that elevation of hs-CRP concentration is an independent predictive parameter of T2DM [32,33] Actually CRP is a most sensitive marker of inflammation and it is associated with features of IR [15,16].…”

“…Resistin, also called FIZZ3 (found in inflammatory zones) or adipocyte secreted factor (ADSF) has been discovered in 2001 while looking for new molecular targets of TZDs in adipocytes [11,33]. It was shown that resistin levels were increased in obese rodents and resistin knock-out mice have lower fasting glycaemia, increased glucose tolerance and insulin sensitivity associated with a reduced liver glucose production [11].…”

“…A number of previous study have reported that high sensitivity (hs) CRP is also related to circulating IL-6 levels [24,32,33] and IL-6 is a powerful inducer of CRP production in the liver [18]. In addition, abdominal obesity is associated with elevated plasma hs-CRP concentration and it has shown that elevation of hs-CRP concentration is an independent predictive parameter of T2DM [32,33] Actually CRP is a most sensitive marker of inflammation and it is associated with features of IR [15,16].…”

“…Some investigations reported that elevated plasma IL-8 concentrations are related to obesity and hyperlipidemia [12]. C-reactive protein (CRP) is an acute-phase reactant, the elevation of which is indicative of acute or chronic inflammation [32,33]. CRP is produced solely by the liver [19].…”

“…CRP is produced solely by the liver [19]. An etiologic role for chronic inflammation in the development of IR has been hypothesized [32,33]. It has been recognized that elevation of CRP concentrations is an independent predictive parameter of T2DM, which is also associated with various components of the metabolic syndrome such as obesity, IR, and dyslipidemia [20][21][22][23][24].…”