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Genetic Polymorphism and Metabolic inflammation in Development of Insulin Resistance and Metabolic Syndrome

Submission Deadline: 31 March 2023 (closed)

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


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.


Endocrine Disrupting Chemicals, Metabolic Disorders, Inflammatory Responses, Oxidative Stress, Insulin Resistance, Metabolic Syndrome, Nutrient-Derived Metabolites, Metabolomics

Published Papers

  • Open Access


    High density lipoprotein as a therapeutic target: Focus on its functionality

    BIOCELL, Vol.47, No.11, pp. 2361-2383, 2023, DOI:10.32604/biocell.2023.031063
    (This article belongs to the Special Issue: Genetic Polymorphism and Metabolic inflammation in Development of Insulin Resistance and Metabolic Syndrome)
    Abstract Cardiovascular diseases (CVDs) are the leading cause of death globally. CVDs are a group of disorders of the heart and blood vessels and include coronary heart disease, cerebrovascular disease and rheumatic heart disease among other conditions. There are multiple independent risk factors for CVD, including hypertension, age, smoking, insulin resistance, elevated low-density lipoprotein cholesterol (LDL-C) levels, and triglyceride levels. LDL-C levels have traditionally been the target for therapies aimed at reducing CVD risk. High density lipoprotein (HDL) constitutes the only lipoprotein fraction with atheroprotective functions. Early HDL-targeted therapies have focused on increasing HDL-C levels. However,… More >

    Graphic Abstract

    High density lipoprotein as a therapeutic target: Focus on its functionality

  • Open Access


    Zinc alpha 2 glycoprotein (ZAG): A potential novel pharmacological target in diabetic retinopathy

    BIOCELL, Vol.47, No.7, pp. 1473-1482, 2023, DOI:10.32604/biocell.2023.027804
    (This article belongs to the Special Issue: Genetic Polymorphism and Metabolic inflammation in Development of Insulin Resistance and Metabolic Syndrome)
    Abstract Zinc alpha 2 glycoprotein (ZAG) is a 41 KDa secretory soluble glycoprotein found in different body fluids like the serum, saliva, sweat, breast milk, and urine. It is also found in tissues like the testis, epididymis, kidney, spleen, liver, lungs, heart, and brain. ZAG is an adipokine with multiple roles, including lipid mobilization, modulating glucose metabolisms, improving insulin sensitivity, inhibiting tumor proliferation through RNAse activity, and suppressing inflammation. Low levels of zinc and ZAG are linked to metabolic syndrome and are also reported as potential biomarkers for diabetic nephropathy. Interestingly zinc has been found to More >

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