Abstract
Nuclear receptors (NRs) are ligand-dependent transcription factors that play essential roles in maintaining metabolic homeostasis and regulating disease progression through the control of metabolism, inflammation, and cellular differentiation. Due to their central position in these pathways, NRs have emerged as critical therapeutic targets in a range of metabolic and cardiovascular disorders, including diabetes, metabolic dysfunction-associated steatotic liver disease ([MASLD]; previously termed non-alcoholic fatty liver disease [NAFLD]), and atherosclerosis. This review summarizes current understanding of the molecular mechanisms by which NRs regulate metabolic function, with particular emphasis on their contributions to disease pathogenesis. We further outline recent advances from preclinical and clinical studies that explore NR-targeted therapeutic strategies. A deeper understanding of NR biology in metabolic and cardiovascular contexts holds promise for the development of more effective and selective interventions.