Immune Cell Remodeling and Chronic Inflammation in Obesity: Implications for Insulin Resistance and Type 2 Diabetes

Obesity is accompanied by chronic low-grade inflammation and increases the risk of type 2 diabetes (T2D), metabolic dysfunction-associated steatotic liver disease, cardiovascular disease, and other inflammatory disorders. Growing evidence indicates that metabolic cues generated in obesity actively reshape immune-cell differentiation and function and thereby contribute to disease progression. In this narrative review, we synthesize recent advances in obesity-associated nutrient excess remodel macrophages, dendritic cells, innate lymphoid cells, and T-cell subsets, emphasizing the evidence linking these changes to adipose inflammation and insulin resistance. We highlight lipid-dependent regulation of the T helper 17 (Th17)/regulatory T (Treg) cell balance, including acetyl-CoA carboxylase 1 (ACC1)-dependent de novo fatty acid biosynthesis and regulation of retinoid-related orphan receptor gamma t (RORγt) by 1-oleoyl-lysophosphatidylethanolamine (LPE [1-18:1]), as a representative mechanism by which cellular metabolism controls lineage-defining transcriptional programs. Finally, we discuss emerging therapeutic approaches, including weight loss and glucagon-like peptide-1 (GLP-1)-based therapies, blockade of inflammatory mediators, reprogramming of immune-cell metabolism, and restoration of inflammation resolution. A better understanding of these metabolic–immune interactions may facilitate the development of new strategies for obesity-associated inflammatory and metabolic diseases.