The Dualistic Effect of COX-2-Mediated Signaling in Obesity and Insulin Resistance

Abstract

Obesity and insulin resistance are two major risk factors for the development of metabolic syndrome, type 2 diabetes and associated cardiovascular diseases (CVDs). Cyclooxygenase (COX), a rate-limiting enzyme responsible for the biosynthesis of prostaglandins (PGs), exists in two isoforms: COX-1, the constitutive form, and COX-2, mainly the inducible form. COX-2 is the key enzyme in eicosanoid metabolism that converts eicosanoids into a number of PGs, including PGD2, PGE2, PGF2α, and prostacyclin (PGI2), all of which exert diverse hormone-like effects via autocrine or paracrine mechanisms. The COX-2 gene and immunoreactive proteins have been documented to be highly expressed and elevated in adipose tissue (AT) under morbid obesity conditions. On the other hand, the environmental stress-induced expression and constitutive over-expression of COX-2 have been reported to play distinctive roles under different pathological and physiological conditions; i.e., over-expression of the COX-2 gene in white AT (WAT) has been shown to induce de novo brown AT (BAT) recruitment in WAT and then facilitate systemic energy expenditure to protect mice against high-fat diet-induced obesity. Hepatic COX-2 expression was found to protect against diet-induced steatosis, obesity, and insulin resistance. However, COX-2 activation in the epidydimal AT is strongly correlated with the development of AT inflammation, insulin resistance, and fatty liver in high-fat-diet-induced obese rats. This review will provide updated information regarding the role of COX-2-derived signals in the regulation of energy metabolism and the pathogenesis of obesity and MS.

Metabolic Syndrome Resolved within Two Years is Still a Risk Factor for Kidney Cancer

“…[32]. It is well known that COX-2 is highly expressed in adipocytes and associated with RCC and insulin resistance [33,34,35]. Increased COX-2 and TNF-α mRNA expression in adipocytes in high-fat rats have been reported [36].…”

Correlative Study on Impaired Prostaglandin E2 Regulation in Epicardial Adipose Tissue and Its Role in Maladaptive Cardiac Remodeling via EPAC2 and ST2 Signaling in Overweight Cardiovascular Disease Subjects

“…In contrast, the truncated soluble isoform, sST2, functioning as a decoy receptor, sequesters IL-33 alarmin protein into extracellular space, preventing ST2L/IL-33 signaling and promoting cardiac and fat tissue maladaptive responses [18]. In view of the role PTGES-2 in obesity and in the control of intracellular cAMP concentrations through PGE 2 receptors [30,32], we investigate the possible association between PTGES-2 and EPAC2 cAMP effector and ST2/IL-33 mechanosensitive genes. We found active expression of EPAC2 in EAT from overweight CVD subjects and an interesting direct association between PTGES-2 and EPAC2 genes EAT mass increases.…”

“…Different studies have noted that the excess accumulation of visceral fat depends on depot-specific expression of key enzymes involved in adipose tissue functions, including PGE 2 biosynthesis-related enzymes [31]. PGE 2 is the principal prostaglandin produced by visceral adipose tissue including EAT deposit [27], which regulates energy metabolism and, particularly in obesity, contributes to fat-inflammation and obesity-related insulin resistance, through the activation of prostaglandin-endoperoxide synthase 2 (PTGES-2) [32], known also as cyclooxygenase 2. PGE 2 regulates adipose functions and exerts its biological effects through its four receptors (EP1, EP2, EP3 and EP4) [27].…”

Therapeutic Strategies with Synbiotics, Thalidomide, and Celecoxib for Severe COVID-19 Pneumonia

“…COX-2 is constitutively overexpressed in association with acute and chronic inflammation and also in malignant tumors 58 . Inflammation induced by pathogens and in response to disordered metabolic states such as obesity is associated with expression of COX-2 59 . Prostaglandin and proinflammatory cytokine production is limited by COX-2 which results in a down-regulation of the cytokine storm 60 and angiogenesis 61 ,62 ,63 .…”