CHEMICAL BIOLOGY OF METABOLIC DISORDERS: TARGETING ENZYMES AND PATHWAYS IN TYPE 2 DIABETES AND OBESITY

Abstract

Both obesity and type 2 diabetes mellitus (T2D) are global health issues that have a heavy economic and societal toll. These two metabolic diseases arise from an intricate interplay of genetic and environmental factors, along with the dysregulation of the biochemical pathways associated with these metabolic disorders. Chemical Biology approaches have emerged as an attractive way to understand and target these metabolic dysfunctions down to the molecular level. This review article aims to discuss the crucial enzymes and pathways perturbed in T2D and obesity, considering their regulation, dysfunction, and therapeutic interventions. Glucokinase, AMP-activated protein kinase (AMPK), and hormone-sensitive lipase modulate glucose and lipid metabolism. Aberrant regulation of these enzymes is linked to insulin resistance, hepatic steatosis, and chronic inflammation, which are hallmark traits of metabolic disorders. Endocrine-disrupting chemicals (EDC) such as bisphenol A (BPA) and phthalates act as metabolic disruptors within this framework by interfering with hormonal signaling and adipogenesis and subsequently accelerating metabolic dysfunction. The shortcomings of currently available pharmacotherapy to treat the metabolically dysfunctional states, including GLP-1 receptor agonists, AMPK activators, and enzyme inhibitors, are evaluated. Nevertheless, there is an urgent need to develop novel targeted interventions that will tackle the primary causes of these metabolic disorders. With development, such therapeutic approaches can benefit from chemical biology tools, like enzyme-specific inhibitors and precision medicine methodologies. Metabolomics, systems biology, and advanced therapeutics discovery require integration and further study to identify new target drugs. Realization of the underlying intricate biochemical networks of T2D and obesity will be important for the rational design of better and more sustainable treatments. This review focuses on just how important chemical biology contributes toward the development of therapeutics in metabolic disorders while calling for coordinated multidisciplinary approaches to tackle these almost acute health challenges..