Elucidating the Mechanisms of Lipid Accumulation in the Liver and Evaluating Potential Drug Targets

Abstract

Fatty liver is defined as a condition in which fat accumulates excessively in the liver. It is characterized by either more than 30% of hepatocytes being fatty or over 5% of the total liver weight attributable to fat. The mechanisms behind hepatic fat accumulation are not fully understood, and no curative treatments have been established; thus, most treatments are symptomatic. Recent studies have focused on the mechanisms involving peroxisome proliferator-activated receptors (PPARs) α and γ, which are central to most research in lipid metabolism and inflammation. However, the development of drugs targeting PPARβ/δ, another isoform, has not progressed as much as for other PPARs. PPARβ/δ is known to play a critical role in maintaining homeostasis in lipid and glucose metabolism, differentiation, and inflammation, similar to other PPAR isoforms, making it a promising target for drug discovery. This review summarizes the potential of PPARβ/δ as a therapeutic target for fatty liver treatment, suggesting that it could be a valuable drug target given its roles in fundamental regulatory mechanisms.