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Resistin, Is There Any Role in the Mediation of Obesity, Insulin Resistance and Type-II Diabetes Mellitus?

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Resistin, Is There Any Role in the Mediation of Obesity, Insulin Resistance and Type-II Diabetes Mellitus? Review Article JOJ Case Stud Volume 6 Issue 3 - March 2018 Copyright © All rights are reserved by Rajeev Pandey DOI: 10.19080/JOJCS.2018.06.555686 Resistin, Is There any Role in the Mediation of Obesity, Insulin Resistance and Type-II Diabetes Mellitus? Rajeev Pandey1* and Gurumurthy2 1Department of Biochemistry, Spartan Health Science University, West Indies 2Department of Neurosciences, Spartan Health Science University, West Indies Submission: February 21, 2018; Published: March 05, 2018 *Corresponding author: Rajeev Pandey, Department of Biochemistry, Spartan Health Science University, St. Lucia, West Indies, Email: Abstract Resistin is a member of a class of cystein-rich proteins collectively termed as resistin-like molecules. Resistin has been implicated in tothe date pathogenesis there has ofbeen obesity-mediated considerable controversy insulin resistance surrounding and T2DM this 12.5kDa(Type II polypeptidediabetes mellitus). in understanding In addition, its resistin physiological also appears relevance to be in a bothpro- inflammatory cytokine. Taken together, resistin, like many other adipocytokines, may possess a dual role in contributing to disease risk. However, involvementhuman and rodent of resistin systems. molecule Furthermore, in the causation this has and led progression question, ofwhether obesity resistin and type represents II diabetes an mellitus important and pathogenicfactors associated factor within the alteration etiology inof theT2DM expression or not. Inof this magicreview, molecule authors athave physiological made an attemptand genetic to discuss levels. the key controversies and developments made so far towards the Keywords: Resistin; Obesity; T2DM; Insulin resistance Introduction Adipose tissue is known to produce a vast array of In addition, we will highlight the continuing complexity of the adipocyte-derived factors, known as adipocytokines. Under in metabolic mechanisms leading to the development of T2DM. biology of resistin and its role in the progression of disease and normal physiological conditions adipocytokines may play the potential interplay between several mechanisms associated (triglyceride) storage and mobilization of fat, with increased an influential role in energy homoeostasis, triacylglycerol in theSince pathogenesis the discovery of T2DM. of resistin in 2001, there have been over be substantially dysregulated [1]. Furthermore, apparently the 260 publications that have informed our present understanding adiposity, specifically central adiposity. These processes can through the concurrent progression of insulin resistance and of controversy and ambiguity surrounding the functional pathogenesis of T2DM (Type II diabetes mellitus) is mediated of its function. This has paradoxically created a maelstrom for this are less understood. It is, however, apparent that obesity resistin over the last few years have been unclear as to whether subclinical inflammation, although the molecular mechanisms significance of resistin. Indeed, researchers outside the field of represents one of the foremost contributory factors leading to this molecule may deserve much attention as an important diabetes, as such; the expression and functional properties of pathogenic factor in the progression of obesity-mediated adipocytokines and their effects on metabolism have been the subject of intense research. Indeed, studies on adipocytokines diabetes. Nevertheless, although several questions remain pertinent to all others, what is the precise physiological function implicated them in the pathogenesis of the metabolic syndrome. unanswered to date regarding resistin, one question remains and their potential effects in human obesity and T2DM have to answer and this review may only highlight some aspects of resistin? Although this is not necessarily an easy question (interleukin)-6, angiotensinogen, leptin, PAI-1 (plasminogen of resistin in disease, it is clear that the physiological role of Such factors include TNF-α (tumour necrosis factor-α), IL resistin is more complex than originally envisioned. Despite an our current understanding of the pathophysiological role of incomplete current understanding of the role of resistin, this activator inhibitor-1) and resistin. This review will address resistin, and evaluate resistin as a pathogenic factor implicated review will assemble and discuss some of the existing literature JOJ Case Stud 6(3) JOJCS.MS.ID.555686 (2018) 001 Juniper Online Journal of Case Studies on resistin evaluating the current metabolic effects of this mechanism for resistin in adipogenesis may occur, acting as an protein, with the intent of providing an insight as to where the adipose sensor for nutritional status. In accordance with these role of resistin may lie. observations, [18] generated transgenic mice over expressing a dominant inhibitory form of resistin which functioned to block The Discovery of Resistin the inhibition of resistin mediated adipocyte differentiation. Resistin, a putative adipocyte-derived signaling polypeptide, enhanced adipocyte differentiation and adipocyte hypertrophy, These transgenic mice developed obesity, possibly owing to as indicated by increased circulating levels of adiponectin and was originally identified by three independent groups using a was up-regulated in rodent models of obesity and insulin leptin [18]. variety of techniques [2,3]. Initial studies showed that resistin resistance and down-regulated by an insulin-sensitizer, RSG Recent investigations of human resistin in relation to obesity have shown higher serum resistin levels in obese subjects (rosiglitazone) [3]; however, immunoneutralization of resistin compared with lean subjects [19-21], which positively correlated reduced hyperglycemia and improved insulin sensitivity [3]. with the changes in BMI (body mass index) and visceral fat area attention, but characterized it as a potential etiological link These observations not only brought resistin to much scientific between obesity and diabetes, with a clear functional role adipose tissue has been corroborated by studies showing as a pathogenic factor contributing to insulin resistance. [21-23]. The implication that resistin is important in human Additionally, this revealed possibilities of the mechanistic action increased protein expression with obesity [23], as well as observations are concomitant with initial studies that showed applications. protein secretion from isolated adipocytes [24]. These recent for TZDs (thiozolidinediones) and their subsequent therapeutic increased serum resistin levels [8] and gene expression levels in The Metabolic Role for Resistin: An Ongoing Debate abdominal depots [6,7] in states of increased adiposity. A further Resistin and obesity levels following moderate weight loss and post-gastric bypass Since the initial investigation of resistin in numerous study has shown significant reduction in circulating resistin [19]. Collectively, these observations suggest resistin could indirectly be subjected to nutritional regulation in humans. experimental data has generated further inconsistency. Human rodent models of obesity and insulin resistance [3,4], ongoing studies have highlighted increased resistin expression in adipose Resistin, insulin resistance and T2DM tissue [5], particularly abdominal depots [6,7]; furthermore, It is currently established that central obesity is a contributing positive correlations between serum resistin and body fat content have also been reported [8]. On the contrary, several factor to the pathogenesis of insulin resistance and consequently studies have failed to demonstrate such correlations in rodents, the data for a role of resistin in obesity, there is a growing body to T2DM. Although, it is apparent that inconsistencies remain in with groups also reporting either reduced [9-11] or no alteration of evidence suggesting a role for resistin in the etiology of insulin [12] of resistin levels in various models of obesity. Although it some instances the same, rodent models, inconsistencies may resistanceIn evaluating and T2DM. resistin and its association with insulin is difficult to address such diverse findings using similar, and in correlations between resistin levels and insulin resistance in sensitivity in humans, several studies have identified positive depend upon methodological differences [13]. vivo [25] and in vitro [26]. Additionally, serum resistin levels had higher circulating resistin levels compared with their lean Studies by [14] showed that various murine models of obesity were increased by approx. 20% in T2DM subjects [24], such by Rajala and coworkers [15], showing circulating resistin levels have reported no associations between serum resistin levels and counterparts. These observations coincided with rodent studies findings have been re-affirmed by [27]. In contrast, other studies of insulin, glucose and lipids; thus substantiating the initial significantly elevated and concordant with increasing levels evidence that addressed the etiology of resistin with increasing markers of insulin resistance in T2DM patients [28-30] or insulin- resistant patients [31]. Moreover, serum and plasma resistin levels were either reduced or increased in T2DM patients with had induced adipocyte differentiation, denoted by fatty acid assessment for insulin resistance), waist circumference, BMI or adiposity [3]. Recently, [16] determined that high-fat-fed mice binding protein (AP-2) gene expression, a surrogate marker of no significant correlation with HOMA-IR (homoeostasis model differentiation,
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