Since 1995, with the discovery of leptin, adipose tissue has been recognized as an active endocrine organ, not only a site for energy storage. The peptide hormones secreted by adipose tissue are collectively called adipocytokines, and include leptin, adiponectin, tumor necrosis factor-α (TNF-α), plasminogen activator inhibitor-1, interleukin-6 (IL-6), and recently described visfatin, apelin, and others. Some adipocytokines including adiponectin, leptin, resistin, TNF-α, IL-6, visfatin and apelin have a close relationship with obesity, insulin sensitivity and type II diabetes.
Adiponectin, also called adipocyte-complement-related protein of 30KD (Acrp 30), is a plasma protein secreted by adipose tissue. Adiponectin mRNA ex
Leptin has been widely accepted as an adiposity signal controlling food intake and energy expenditure. Plasma leptin levels are positively related to the fat mass and are significantly increased in obese, type II diabetic, and insulin resistant patients. Mice that are deficient in leptin (obese, ob/ob) or leptin receptor (diabetic, db/db) exhibit hyperphagia, obesity, and diabetes. Exogenous leptin administration to ob/ob mice reverses these abnormalities. Leptin binds to its receptors located in hypothalamic arcuate nucleus, activates neurons that express proopiomelanocortin (POMC) to release anorexic neuropeptide, α-MSH, and inhibits neurons that express orexigenic neuropeptide Y (NPY) and agoutirelated protein (AgRP), which potently stimulate food intake and metabolic efficiency. α-MSH binds to and acts on melanocortin 4 receptors (MC4R) located in downstream neurons in paraventricular nuclei (PVN) and the lateral hypothalamus (LH), thus decreasing food intake and increasing energy expenditure actions, which are mediated in part by corticotrophin releasing hormone (CRH) and oxytocin. α-MSH also increases the gene ex
Fig.1 The normal lipid metabolism regulated by leptin.
Resistin is recognized as an anti-adipogenic factor and an inducer of insulin resistance. It inhibits adipocyte differentiation, impairs glucose tolerance, decreases insulin-mediated glucose uptake, and increases hepatic glucose production. Plasma resistin levels were reported to be elevated in the genetic (ob/ob) and high-fat-diet- induced obese mice and in insulin-resistant animals. Resistin administration to normal mice impaired glucose tolerance and action of insulin. Anti-diabetic treatment with thiazolidinediones (TZD) reduced resistin gene ex
TNF-α and IL-6, proinflammatory cytokines involved in chronic inflammation and malignancy, now are well documented as adipocytokines contributing to insulin resistance. The mRNA ex