Obesity, diabetes, and inflammation: Pathophysiology and clinical implications

Abstract

Obesity and its related disorders, including type 2 diabetes and liver, kidney, and cardiovascular diseases, are now recognized as chronic inflammatory conditions. Here, we review the mechanisms underlying inflammation in these settings and how they may contribute to pathology. Nutrient excess triggers immune activation through pattern recognition receptors and the NLRP3 inflammasome, leading to interleukin (IL)-1β production and downstream cytokine cascades. Initially adaptive, this inflammation promotes tissue remodeling and metabolic compensation, but chronic activation contributes to insulin resistance, β cell dysfunction, and end-organ damage. We discuss the current therapeutic options, with a focus on glucagon-like peptide-1 (GLP-1) receptor agonists, which, alone or combined with additional bioactive moieties, exert notable anti-inflammatory effects. Some effects of GLP-1 medicines are independent of glucose control or weight loss, and they are attributed to direct signaling via the immune GLP-1 receptor (GLP-1R) and, indirectly, via central nervous system circuits. Understanding these mechanisms may unlock further therapeutic potential in chronic inflammatory diseases.

Keywords: GLP-1; IL-1; NLRP3; diabetes; inflammation; obesity.