Obesity, a chronic multifaceted disease, predisposes its individuals to increased risk of metabolic disorders such as: diabetes mellitus, cardiovascular diseases, dyslipidemia, etc. the development of obesity and its mediated metabolic dysregulation. In Avasimibe pontent inhibitor view of the increasing prevalence of obesity globally and the potential threat it places on life expectancy, this article reviewed the promising potentials of targeting endogenous secretory receptor for advanced glycation end products/soluble receptors for advanced glycation end products signaling as a treatment approach for obesity. We carried out a literature search in several electronic data bases such as: Pubmed, Pubmed Central, Google, Google Scholar, Scopus, and Medline from 1980 to 2019 to acquire the status of information concerning this. The article suggests the need for the development of an esRAGE/sRAGE targeted pharmacotherapy as a treatment approach for obesity and its comorbidity. strong class=”kwd-title” Keywords: obesity, nutrition, metabolic dysregulation, receptor for advanced glycation end products, metabolic syndrome Introduction Obesity is a chronic metabolic disease that is characterized by excess body fat as a result of hyperplasia and hypertrophy of the adipocytes (Renata et al., 2018; Egedigwe-Ekeleme et al., 2019). Obesity which can be induced by overnutrition and characterized by inflammation and oxidative stress, predisposes its patients to increased risk of diabetes mellitus (T2DM), cardiovascular diseases, dyslipidemia, cancer, etc. RGS5 (Priyanto et al., 2016; Richard et al., 2019). Furthermore, recent studies reported it to be one of the leading cause of deaths in the world with an annual mortality rate of 2.8C3.4 million (Egedigwe et al., 2016; Priyanto et al., 2016; Victoria et al., 2018). Although there are many options for the treatment of this disease such as dietary management, exercise, life-style changes, weight-loss medications, and weight-loss surgeries (Nan-Nong et al., 2016), many of them have not been able to successfully reverse obesity and its associated metabolic dysregulation or comorbidity (Burke et al., 2018). The receptor for advanced glycation end products (RAGE) was reported to be a multi-ligand cell surface protein (Miranda et al., 2018). When bound to its ligand, RAGE initiates an inflammatory signaling cascade, that leads to the activation of nuclear factor kappa B (NF-B) and transcription of inflammatory cytokines. This action has been associated with the development of obesity and its co-morbidity (Vazzana et al., 2012). Therefore, attenuation of the signaling of RAGE has been suggested as a veritable approach for the treatment of obesity and its comorbidity (Miranda et al., 2018). The isoforms of the soluble receptors for advanced glycation end products (sRAGE) act as decoy receptors for RAGE by sequestering RAGE ligands and attenuating RAGE signaling. These isoforms include: cleaved RAGE (cRAGE) which is produced through proteolytic shedding of the RAGE and the endogenous secretory RAGE (esRAGE) which is formed by splicing of the pre-RNA of RAGE (Miranda et al., 2018). Recently, several therapeutic properties have been credited to these sRAGE such as: antidiabetic, anti-inflammatory, and antioxidant Avasimibe pontent inhibitor properties (Parisa and Ali, 2011; Lorenzi et al., 2014; Miranda et al., 2018) and for which some reviews are available on them in literature. Surprisingly, reviews on the potential usefulness of these decoy receptors as targets for the treatment of obesity are lacking in literature. Given the increasing prevalence of obesity and its comorbidity globally, the need to diversify its treatment approach has become a necessity. Since attenuation of the signaling of Trend Avasimibe pontent inhibitor continues to be suggested as an advantageous strategy for the treating obesity and its own comorbidity and becoming these isoforms of Trend become decoy receptors for Trend, diminishing its signaling (Miranda et al., 2018), today’s article evaluated the idea of focusing on of esRAGE and sRAGE signaling as an advantageous strategy for the treating obesity. Components and Strategies We carried out our books search in a number of digital data bases such as for example: Pubmed, Pubmed Central, Google, Google Scholar, Scopus, and Medline from 1980 to 2019 to get the current position of information concerning our idea using keywords such as for example: weight problems, T2DM, advanced glycation end items (Age groups), Trend, esRAGE, and sRAGE. The findings we got from these data bases are reported with this review hereby. Definition of Weight problems Weight problems could be thought as a persistent multifaceted disease that’s characterized by excessive body fat because of hyperplasia and hypertrophy of adipocytes (Renata et al., 2018). It really is a condition that is associated with.