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

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.

Lipid Droplet Biosynthesis Impairment through DGAT2 Inhibition Sensitizes MCF7 Breast Cancer Cells to Radiation

“…However, we observed a downregulation of PLIN5 gene expression following irradiation that was fostered by the combined treatments. It has been shown that PLIN5 protects against lipotoxicity mainly in oxidative tissues [ 6 , 41 ], thus the downregulation observed with the combined treatments may indicate a reduced ability of the cells to deal with the oxidative stress, which, in turn, could be implicated in increased radiosensitization. It is worth noting that, as expected, PF-06424439 treatment significantly reduced the transcript levels of DGAT2, which were further decreased by the combined treatment soon after IR.…”

Mitochondrial Lipid Homeostasis at the Crossroads of Liver and Heart Diseases

“…PLIN5 is a promising therapeutic target for NAFLD and atherosclerosis, and possibly for some other metabolic diseases. We wish to redirect interested readers to recent reviews for further information about the role of PLIN5 and mitochondria-LD contact sites in the development of NAFLD and other diseases [109,110].…”

Lipid Droplets, Phospholipase A2, Arachidonic Acid, and Atherosclerosis

“…PLIN4 has been implicated in stabilizing the LD by interacting directly with TG moieties when their phospholipid coverage is limited [ 8 ]. PLIN5 appears to be involved in protective roles against mitochondrial damage and endoplasmic reticulum stress in liver [ 9 ].…”