PPAR Alpha as a Metabolic Modulator of the Liver: Role in the Pathogenesis of Nonalcoholic Steatohepatitis (NASH).

Abstract

Simple SummaryIn the context of liver disease, one of the more growing public health problems is the transition from simple steatosis to non-alcoholic steatohepatitis. Profound metabolic dysregulations linked to inflammation and hepatic injury are features of non-alcoholic steatohepatitis. Since the peroxisomal-proliferator-activated receptor alpha has long been considered one of the key transcriptional factors in hepatic metabolism, its role in the pathogenesis of non-alcoholic steatohepatitis is discussed in this review.The strong relationship between metabolic alterations and non-alcoholic steatohepatitis (NASH) suggests a pathogenic interplay. However, many aspects have not yet been fully clarified. Nowadays, NASH is becoming the main cause of liver-associated morbidity and mortality. Therefore, an effort to understand the mechanisms underlying the pathogenesis of NASH is critical. Among the nuclear receptor transcription factors, peroxisome-proliferator-activated receptor alpha (PPARα) is highly expressed in the liver, where it works as a pivotal transcriptional regulator of the intermediary metabolism. In this context, PPARα’s function in regulating the lipid metabolism is essential for proper liver functioning. Here, we review metabolic liver genes under the control of PPARα and discuss how this aspect can impact the inflammatory condition and pathogenesis of NASH.