GLP-1/GLP-1R axis: from metabolism (obesity and T2DM) to immunity

The discovery of glucagon-like peptide-1 (GLP-1) has revolutionized metabolism research in the context of obesity and type 2 diabetes mellitus (T2DM). For example, worldwide, more than 537 million adults are affected with T2DM, and more than 30.3 million people in the USA alone are suffering from T2DM. Obesity is one independent risk factor for T2DM; therefore, targeting obesity may lower the T2DM development risk. Hence, pharmaceutical companies have developed different GLP-1R agonists (GLP-1RAs) to target obesity and T2DM, which comprised multibillion-dollar businesses. However, metabolism and immune response are well-correlated processes that affect each other. For example, recent advances in metabolic processes governing the immune response have led to the evolution of immunometabolism, which can be divided into cellular, tissue and systemic immunometabolism. The current open-question article is intended to explore the impact of the GLP-1/GLP-1R axis on the immune response governed by the functioning of various immune cells and their interaction with the nervous system and microbiota axis that further depends on the gender and circadian clock of the host. Along with food/sugar ingestion, several other factors controlling the GLP-1 secretion and its immunomodulatory functions have been discussed to highlight the importance of the GLP-1/GLP-1R axis in immunoregulation. Therefore, understanding the GLP-1/GLP-1R axis/interaction at the immunological level will help to understand the adverse events associated with GLP-1RAs and their use as an immunomodulatory agent in acute and chronic inflammatory conditions depending on the gender and metabolic status of the host.