Understanding the Role of Perilipin 5 in Non-Alcoholic Fatty Liver Disease and Its Role in Hepatocellular Carcinoma: A Review of Novel Insights.

Paola Berenice Mass Sanchez,Anastasia Asimakopoulos,Ralf Weiskirchen,Marinela Krizanac

doi:10.3390/ijms22105284

Abstract

Consumption of high-calorie foods, such as diets rich in fats, is an important factor leading to the development of steatohepatitis. Several studies have suggested how lipid accumulation creates a lipotoxic microenvironment for cells, leading cells to deregulate their transcriptional and translational activity. This deregulation induces the development of liver diseases such as non-alcoholic fatty liver disease (NAFLD) and subsequently also the appearance of hepatocellular carcinoma (HCC) which is one of the deadliest types of cancers worldwide. Understanding its pathology and studying new biomarkers with better specificity in predicting disease prognosis can help in the personalized treatment of the disease. In this setting, understanding the link between NAFLD and HCC progression, the differentiation of each stage in between as well as the mechanisms underlying this process, are vital for development of new treatments and in exploring new therapeutic targets. Perilipins are a family of five closely related proteins expressed on the surface of lipid droplets (LD) in several tissues acting in several pathways involved in lipid metabolism. Recent studies have shown that Plin5 depletion acts protectively in the pathogenesis of liver injury underpinning the importance of pathways associated with PLIN5. PLIN5 expression is involved in pro-inflammatory cytokine regulation and mitochondrial damage, as well as endoplasmic reticulum (ER) stress, making it critical target of the NAFLD-HCC studies. The aim of this review is to dissect the recent findings and functions of PLIN5 in lipid metabolism, metabolic disorders, and NAFLD as well as the progression of NAFLD to HCC.

Highlights

Lipid accumulation in the liver plays a pivotal role in the pathogenesis of non-alcoholic fatty liver disease (NAFLD) that might result from dysfunction of cellular lipid trafficking and lipid droplet formation
The enzymes involved in this biosynthesis of sterols are acetyl-CoA acetyltransferases 1 and 2 (ACAT1 and ACAT2), whereas TAGs are the product of diacylglycerol acyltransferases (DGAT1 and DGAT2)
The results indicate that phosphorylation of PLIN5 by protein kinase A (PKA) triggers PLIN5 nuclear translocation during fasting and lipolysis conditions when PLIN5 binds to the promoter region of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) [66]

Summary

Introduction

Lipid accumulation in the liver plays a pivotal role in the pathogenesis of NAFLD that might result from dysfunction of cellular lipid trafficking and lipid droplet formation. Several enzymes are located in ER, helping the formation, stabilization, and degradation of LDs. Several enzymes are located in ER, helping the formation, stabilization, and degradation of LDs These proteins belong to the perilipin/PAT family, the Ras superfamily of GTPases (Rab), and ADP-ribosylation factor1-coat protein complex I (Arf-COPI) [3]. In this context, the general structure of LD consists of a central core of TAG and cholesterol esters, while a peripheral monolayer is composed of phospholipids with attached proteins with structural and functional roles as depicted in Figure 1 [1]

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Conclusion