Human resistin and the RELM of Inflammation in diabesity

Abstract

The initial discovery of resistin and resistin-like molecules (RELMs) in rodents suggested a role for these adipocytokines in molecular linkage of obesity, Type 2 Diabetes mellitus and metabolic syndrome. Since then, it became apparent that the story of resistin and RELMs was very much of mice and men. The putative role of this adipokine family evolved from that of a conveyor of insulin resistance in rodents to instigator of inflammatory processes in humans. Structural dissimilarity, variance in distribution profiles and a lack of corroborating evidence for functional similarities separate the biological functions of resistin in humans from that of rodents. Although present in gross visceral fat deposits in humans, resistin is a component of inflammation, being released from infiltrating white blood cells of the sub-clinical chronic low grade inflammatory response accompanying obesity, rather than from the adipocyte itself. This led researchers to further explore the functions of the resistin family of proteins in inflammatory-related conditions such as atherosclerosis, as well as in cancers such as endometrial and gastric cancers. Although elevated levels of resistin have been found in these conditions, whether it is causative or as a result of these conditions still remains to be determined.

Diabesity Increases Inflammation and Oxidative Stress

“…Chronic inflammation as a result of several pro-inflammatory markers such as cytokines and chemokines have been shown to precede weight gain and obesity [9]. Similar observations are seen with a number of oxidative stress [17,19,20]. IGF-1 functions in association with insulin-like growth factor binding protein-1 (IGFBP-1) [21].…”

“…Increased levels of 8-iso-PGF 2α accompanied by an increase in urinary 8-OHdG levels correlating to body mass index (BMI) have been reported in diabesity [11,37]. Several inflammatory markers have also been suggested [19]. The role of inflammatory markers and oxidative stress and how these interact in diabesity has not been extensively investigated when compared to T2DM and obesity and is therefore explored in this study.…”

Training Dieters to Eat Intuitively with a Mobile Application

“…Lifestyle interventions focused on weight loss are often intensive, expensive, and temporary, with most people regaining weight within two to four years (Anderson, Gutierrez, Kennedy, & Hasty, 2013;Gaesser, Angadi, Sawyer, Tucker, & Jarrett, 2014;Montani, Schutz, & Dulloo, 2015). Furthermore, regained weight is often met with repeated bouts of dieting, or weight cycling, which may be more harmful metabolically than simply being overweight, (Montani et al, 2015) as the regained weight is more likely to be visceral (truncal) fat (Al Hannan & Culligan, 2015;Ouchi, 2016). Visceral fat is especially unhealthy and linked to insulin resistance and inflammation, both precursors of cardiometabolic disease (Al Hannan & Culligan, 2015;Park, Kwak, Kim, & Ahima, 2017)).…”

Novel targets for the development of drugs for Type 2 Diabetes Mellitus

“…Resistin plays an important role in insulin resistance and in inflammation (Mojiminiyi et al, 2007;McTernan et al, 2006;Holcomb et al, 2000;Fasshauer and Blüher, 2015). Several mechanisms have been proposed for resistin's activity such as inhibition of cell surface glucose transporters, activation of suppressors of cytokine signaling (SOCS-3), blocking of insulin signaling pathways, stimulation of hepatic glucose production and activation of free fatty acids release from adipose tissue (Moon et al, 2003;Steppan et al, 2005;Brown et al, 2007;Sheng et al, 2008;Banerjee et al, 2004;Pravenec et al, 2006;Stofkova, 2010;Fasshauer and Blüher, 2015;Al Hannan and Culligan, 2015). Additionally resistin promotes overall inflammation through TLR-4 (Benomar et al, 2012).…”

“…This extended comparison might shed light on the actual mechanism behind resistin mediated effects in T2DM and reveal possible biomarkers that could be resistin's receptor or could be used as potential novel pharmacological targets. All the above possible findings have to be translated into human subjects considering the fact that human and mouse resistin are not homologous (Al Hannan and Culligan, 2015;Park et al, 2013;Ghosh et al, 2003;.…”