Roles of peroxisome proliferator-activated receptors (PPARs) in pancreatic metabolic diseases

The peroxisome proliferator-activated receptors (PPARs), including PPAR-α, PPAR-β/δ, and PPAR-γ, are nuclear receptors that play critical roles in regulating metabolism and inflammation. While PPARs have been extensively investigated in classical metabolic disorders such as metabolic dysfunction-associated steatotic liver disease (MASLD), type 2 diabetes, and lipid metabolism disorders, their roles in pancreatic metabolic diseases remain underexplored. Given the absence of a systematic review on this topic, the present review provides a comprehensive overview of the mechanisms and therapeutic potential of PPAR subtypes in pancreatic metabolic conditions, including fatty pancreas (FP), hypertriglyceridemic pancreatitis (HTGP), and pancreatogenic diabetes. PPARs contribute to the pathogenesis and progression of these diseases by modulating lipid metabolism, inflammatory responses, and β-cell function. By integrating molecular insights with clinical evidence, this review highlights the lipid-modulating and anti-inflammatory effects of PPAR-targeted therapies and discusses their associated clinical benefits and risks. The aim is to establish a theoretical foundation for novel therapeutic strategies in pancreatic metabolic diseases. Nevertheless, preclinical and clinical studies in this area remain limited, and direct clinical evidence supporting the efficacy of PPAR agonists in pancreatic contexts is currently lacking. Further research is warranted to elucidate the direct therapeutic efficacy of PPAR agonists in pancreatic metabolic diseases.