Guest Editors
Dr. M. Sajid Hamid Akash, Department of Pharmaceutical Chemistry, Government College University, Pakistan. sajidakash@gmail.com
Dr. Kanwal Rehman, Department of Pharmacy, The Women University, Multan, Pakistan. Email: kanwalrehman@wum.edu.pk
Summary
Insulin resistance (IR) is characterized by the presence of high circulating levels of insulin and the cell’s inability to metabolize glucose for energy production resulting in a persistent hyperglycemic condition. IR is considered to be an underlying cause of developing metabolic syndrome (MetS) that includes obesity, type-2-diabetes etc. In MetS, excessive nutrient energy intake and a defective energy homeostasis alter biochemical pathways of metabolism and the immune system that is often associated with a chronic pro-inflammatory condition leading to IR. One mechanism of IR includes the interaction of metabolites with the toll-like receptors (TLR) molecules particularly the TLR-4 and TLR- 2 and activation of associated inflammatory cascades closely similar to those involved in the process of pathogenic infection. Common biochemical pathways activated by the nutrient derived metabolites as well as the immune system mediators were originally evolved to provide survival advantage when nutrient energy supply is limited, and the pathogenic burden is high. However, under the condition of excessive nutrient energy- a hallmark of MetS, the biochemical pathways alter, and the delicate balance of metabolism and immunity is lost.
Nutrient-derived metabolites such as free fatty acids (FFA), saturated fatty acids (palmitate), diacylglycerol (DAG) etc. were reported to induce TLR-4 mediated innate immune response. The mechanisms of interaction of these nutrient-derived metabolites with the TLRs are being widely investigated by a number of leading groups and more and more interesting details are emerging. For example, FFA needs to bind to an intermediate molecule Fetuin A to activate TLR-4 and its associated inflammatory cascades, while the presence of TNF-α exacerbated the pro-inflammatory response induced by the saturated fatty acid palmitate. In contrast, the nutrient-derived metabolites such as poly-unsaturated fatty acids, polyphenols etc. can also inhibit the TLR-4 mediated pathways leading to an anti-inflammatory cellular environment. Nevertheless, more research is needed to understand the threshold level at which these nutrient-derived metabolites start behaving like infectious particles and the exact underlying cause of such a shift in the biochemical pathways. While the contributions of gut microbiome are highly relevant for metabolic inflammation in MetS, the roles of nutrient-derived metabolites in the gut particularly the short-chain fatty acids and their intricate interactions with the lipopolysaccharide- a strong inducer of TLR-4 and its associated inflammatory cascades in metabolic inflammation particularly in the context of IR need to be understood. In addition, the presence of diverse molecular pathways leading to metabolic inflammation by various metabolites should be explored in understanding the mechanism of IR as well as devising preventative/therapeutic strategies.
This special issue invites primary manuscript, review articles and case studies in the following areas:
▪ Mechanism of TLRs-mediated metabolic inflammation.
▪ Biochemical pathways of activation/inhibition of TLRs-mediated immune cascades by nutrient-derived metabolites.
▪ Gut metabolites and their mode of action and interaction with other metabolites in development/prevention of metabolic inflammation and IR.
▪ Association of endocrine disrupting chemicals (EDCs) with metabolic syndrome.
▪ Role of EDCs in the impairment of carbohydrate and lipid metabolizing enzymes.
▪ Association of Genetic polymorphism in development of metabolic syndromes.
Keywords
Endocrine Disrupting Chemicals, Metabolic Disorders, Inflammatory Responses, Oxidative Stress, Insulin Resistance, Metabolic Syndrome, Nutrient-Derived Metabolites, Metabolomics
Published Papers
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