Highlights

• This review uniquely focuses on how all three peroxisome proliferator-activated receptors (PPARs) isoforms interact with multiple pathological mechanisms of nonalcoholic fatty liver disease (NAFLD) through a single regulatory lens.
• It integrates recent findings that link PPARα activation to the modulation of oxidative stress, inflammation, and insulin resistance in a tissue-specific manner.
• The article suggests that endogenous PPAR ligands from lipid metabolism may serve as both biomarkers and therapeutic targets in NAFLD treatment.

Summary

The research reviews the roles of peroxisome proliferator-activated receptors (PPARs), specifically PPARα, PPARβ/δ, and PPARγ, in the development and potential treatment of nonalcoholic fatty liver disease (NAFLD).

PPARs regulate genes related to lipid metabolism, inflammation, oxidative stress, and insulin resistance, which are central to NAFLD pathogenesis. PPARα is primarily involved in fatty acid oxidation and energy metabolism in the liver, while PPARγ controls adipocyte differentiation and insulin sensitivity, and PPARβ/δ influences lipid handling and inflammation. Therapeutic activation of these receptors through endogenous or synthetic ligands shows great potential in managing NAFLD but is complicated by side effects such as oxidative stress and cardiovascular risks.

The article emphasizes the potential of PPAR-targeted therapies while acknowledging the need for further research into their mechanisms and safety.

Y.-Y. Qiu, J. Zhang, F.-Y. Zeng, and Y. Z. Zhu, “Roles of the peroxisome proliferator-activated receptors (Ppars) in the pathogenesis of nonalcoholic fatty liver disease (Nafld),” Pharmacological Research, vol. 192, p. 106786, Jun. 2023, doi: 10.1016/j.phrs.2023.106786