Different Kinds of Adipokines - Report Example

Adipokines Number Adipokines, also commonly referred to as adipocytokines, are cytokines (cell stimulating proteins/ chemical messengers) that are secreted by the adipose tissue (Fantuzzi, 2007). The term adipocytokine is itself derived from three Greek words – ‘adipo’ meaning fat, ‘cytos’ meaning cell and ‘kines’ which denotes movement. Adipokines include inflammatory mediators, angiogenic proteins and metabolic regulators some of which, such as leptin, adiponectin and resistin are produced foremost in the adipose tissue while others like tumor necrosis factor alpha, interleukin-6 and the monocyte chemostatic protein-1 are produced from other tissues. Adipokines are said to play critical roles in a number of biological processes such as glucose and fatty acid metabolism, insulin sensitivity and adipocyte differentiation since they can act locally or peripherally in the body. In addition to these functions, adipokines also confer functions as mediators linking obesity, during inflammation reactions, immunity and other obesity related diseases. Some of the most common types of adipokines are leptin, adiponectin, apelin, chemerin, interleukin-6 (IL-6), monocyte chemostatic protein-1, plasminogen activator inhibitor-1, tumor necrosis factor, visfatin, interleukin-8, interleukin-10, interferon gamma, inducible protein 10, adipsin and resistin among others (Jaedicke, 2010). Some adipokines like the adiponectin, visfatin and omentin are known to function as insulin sensitizing adipokines while TNF, IL-6 and resistin, on the other hand, are examples of those that induce insulin resistance. Obesity is a major risk factor of a number of clinical manifestations such as diabetes, cardiovascular diseases and certain cancers. Regardless of the underlying genetic and environmental determinants, the root cause of obesity is energy imbalance. Obesity is primarily characterized by excess body fat or white adipose tissue within which are adipokines which store fat. Increase in fat that causes obesity is caused by a combination of differentiation of preadipocytes and size increase of mature adipocytes. Currently, the white adipose tissue (and adipokines) continues to attract massive attention in obesity research as it has been observed as a source of endocrine and paracrine signaling molecules vital in a myriad of physiological and metabolic processes. Insulin resistance and coronary diseases appear to be closely associated with visceral fat deposits (Taylor, 2005). Obesity is characterized by a chronic, low-grade pre-inflammatory state causing hyperplasia and hypertrophy of fat cells leading to an imbalance in the release of adipokines which consequently causes reduction in insulin sensitivity and an increase in contractility and inflammation leading to vascular diseases like hypertension, artherosclerosis and vascular dysfunction. Endothelial dysfunction is characterized by impaired nitric oxide (NO) release from endothelium and decreased blood flow to insulin target tissues contributing to insulin resistance. Systemic inflammation and abnormal production of adipose tissue-derived factors play a vital function in the genesis and progression of atheriosclerosis accompanied by endothelial cell dysfunction and altered expression of pro-angiogenic or pro-atherogenic factors such as matrix metalloproteinases and vascular endothelial growth factor leading to changes in structure and function of endothelium (Fantuzzi, 2007). Different adipokines as discussed below have different effects on diabetes and vascular conditions. Medical researchers have since rampantly sought to use these different functions to achieve the treatment of the above mentioned conditions. Further study/ investigation on the role of the different types of adipokines is currently underway in major research institutions and universities world-wide to find suitable and effective means of counteracting these conditions that have so direly ravaged mankind overtime. Resistin Resistin’s over-expression results in insulin resistance and dyslipidaemia and increased levels are observed in obesity. Resistin inhibits cellular glucose uptake. Experiments indicate that leptin suppresses resistin’s mRNA expression and protein levels which reduces glucose and insulin. High levels of resistin in blood correlate with pro-atherogenic inflammatory markers, increased cardiovascular risk, unstable angina and poor prognosis in coronary artery disease (Preedy, 2011). Omentin Omentin stimulates insulin mediated glucose transport in adipokines and triggers Akt signaling with its expression greater in visceral tissue than in adipose tissue. Omentin plays an important role in cardiovascular disease pathogenesis like in coronary atherosclerosis, as the absence of fibrous fascial layers allows for more diffusion of adipokines and free fatty acids between epicardial adipose tissue and the underlying vessel wall in addition to the myocardium. It induces vasodilation and inhibits EC migration, angiogenesis and vascular inflammation. Omentin 1 adipose tissue gene expression and plasma levels are decreased in obesity and correlate negatively with BMI, insulin resistance and waist circumference (Jaedicke, 2010). Leptin Leptin is a hormone which controls the amount of fat stored in the body by controlling the sensation of hunger and energy usage. When the amount of fat stored in the body reaches a certain level, for example, hunger is inhibited and energy expenditure increased by signals to the brain and through leptin receptors on peripheral targets. The Ob(Lep) gene, about 16kDa protein of 176 amino acids, is located in chromosome 7 in humans. It is produced mainly by the white adipose tissue but is also yielded by the brown adipose tissue, placenta, ovaries, skeletal muscles, stomach, mammary epithelial cells, bone marrow, pituitary, liver, gastric chief cells and P/D1 cells. Leptin plays role in adaptive response to starvation and levels are decreased after short-term fasting. Sleep deprivation and physical exercise reduce serum levels of leptin. Its levels on the other hand are increased by insulin, during obesity, by dexamethasone and emotional stress. In obese patients, with obstructive sleep apnea, leptin levels are increased but decreased after administration of continuous positive airway pressure. Leptin levels are decreased or increased by increases in testosterone and estrogen levels respectively (Taylor, 2005). In an experiment using rats, leptin was shown to regulate immune response to artherosclerosis of which obesity is a risk factor. In addition, it is shown that leptin can by increasing vascular endothelial growth factor levels promote angiogenesis. Apart from leptin inducing sympathoexcitatory responses and potentiating cardiovascular reactions to the activation of the chemoreflex, hyperleptinemia has been shown to decrease blood pressure. Adiponectin Adiponectin, encoded by ADIPOQ gene, is a 244 amino acid long polypeptide with four distinct regions, whose primary function is glucose level regulation and fatty acid breakdown (oxidation). It is exclusively secreted from the adipose tissue and into the bloodstream. In adults, levels of adiponectin are inversely proportional to the amount of fat in the body. Increased adiponectin levels lead to impaired adipocyte differentiation and increased energy usage from protein coupling. Because of its function in the suppression of metabolic derangements, adipokine may result in type II diabetes, obesity, atherosclerosis, non-alcoholic fatty liver disease and an independent risk factor for metabolic syndrome (Preedy, 2011). Further experimental research indicates that a combination of adiponectin and leptin completely reverses insulin resistance. Levels of adiponectin are reduced in diabetics and males and are higher in non-diabetics and females. Research also shows that high molecular weight forms of adiponectin are most active in glucose homeostasis and are associated with lower risks of diabetes. However, high molecular weight adiponectin can result in coronary artery disease. Apelin Apelin, encoded by APLN gene, is commonly expressed in a number of organs like the heart, lung, kidney, liver, adipose tissue, gastrointestinal tract, brain, adrenal glands, endothelium and human plasma. Apelin participates in the regulation of blood pressure and additionally functions to enhance formation of new blood vessels/ angiogenesis. Apelin also induces relaxation of the smooth muscle cells of the artery walls, regulates vasoconstriction and consequently blood pressure (Jaedicke, 2010). Chemerin Chemerin functions in growth inhibitory, cell differentiation activities and treatment of hyper proliferative dermatological diseases. It is a 14kDa protein secreted in an inactive form, prochemerin, and activated via cleavage of the C-terminus by inflammatory and coagulation serine proteases. It is important in glucose uptake and adipocyte differentiation. It increases the expression of the insulating receptor and interleukin-6 while also playing role in energy storage. Chemerin also plays a role in chreonic inflammation of the adipose tissue in obesity/ pathogenesis of obesity and insulin resistance. Experiments reveal that feeding mice on a high fat diet increases expression of chemerin. Chemerin levels in humans are almost steady even when those of patients with type II diabetes and those with normal glucose tolerance are compared. Research also suggests that adipokine is important in insulin sensitivity and may be useful hence in the treatment of type II diabetes (Preedy, 2011). Visfatin Visfatin/ nicotinamide phosphoribosyltransferase/ pre-B-cell colony enhancing factor promotes vascular smooth cell maturation, inhibits neutrophil apoptosis, activates insulin receptor and has insulin mimic effects which lowers blood glucose and improves insulin sensitivity. The protein is predominantly expressed in visceral fat and serum levels of the protein correlate with obesity (Fantuzzi, 2007). References Fantuzzi, G. (2007). Adipose tissue and adipokines in health and disease. Totowa, N.J.: Humana Press. Jaedicke, K. M. (2010). Adipokines and myeloid cell immune responses in periodontal disease and diabetes. Newcastle upon Tyne: University of Newcastle upon Tyne. Preedy, V. R. (2011). Adipokines. Enfield, N.H.: Science Publishers ;. Taylor, R. B. (2005). Taylors cardiovascular diseases a handbook. New York, NY: Springer. Read More