Author: Amina Al-Fahad, Yousef Al-Qahtani
Review Article
Functional Role of Perilipins in Lipid Droplet Biogenesis and Expansion
Amina Al-Fahad¹* and Yousef Al-Qahtani²
¹Department of Microbiology, King Saud University, Riyadh, Saudi Arabia
2Department of Biotechnology, King Abdulaziz University, Jeddah, Saudi Arabia
Published: 16 October 2017
Abstract
Lipid droplets (LDs) are dynamic intracellular organelles that serve as essential reservoirs for neutral lipids, including triglycerides and cholesterol esters. These structures play a pivotal role in cellular energy homeostasis, acting as metabolic hubs that regulate lipid storage, mobilization, and utilization. The formation and maintenance of LDs are tightly controlled by a family of proteins known as perilipins (PLINs), which serve as key regulators of lipid metabolism. PLIN proteins modulate LD stability, expansion, and interaction with lipolytic enzymes, influencing lipid turnover and cellular energy balance. The PLIN family consists of five isoforms (PLIN1–PLIN5), each with distinct tissue distributions and functions. PLIN1 is primarily expressed in adipocytes and plays a crucial role in regulating lipolysis by modulating the activity of hormone-sensitive lipase (HSL) and adipose triglyceride lipase (ATGL). PLIN2, widely expressed in non-adipose tissues, contributes to LD formation and lipid sequestration. PLIN3 facilitates lipid trafficking and LD biogenesis, whereas PLIN4 is predominantly found in white adipose tissue and influences lipid accumulation. PLIN5, highly expressed in oxidative tissues such as skeletal muscle and liver, coordinates lipid storage with mitochondrial β-oxidation, ensuring an optimal balance between energy storage and consumption. LD expansion is a tightly regulated process involving PLIN proteins, phospholipid remodeling, and interactions with key metabolic enzymes. The recruitment of lipogenic factors to LDs enhances lipid accumulation, while selective proteolysis and phosphorylation events determine the fate of stored lipids. Dysregulation of PLIN-mediated LD dynamics has been implicated in various metabolic disorders. Excessive lipid accumulation due to impaired lipolysis contributes to obesity, insulin resistance, and type 2 diabetes, whereas defects in LD formation are linked to lipodystrophies and fatty liver disease. Recent studies have highlighted the therapeutic potential of targeting PLIN proteins to modulate lipid metabolism and improve metabolic health. Pharmacological interventions that enhance PLIN-mediated lipid storage in adipose tissue while preventing ectopic lipid accumulation in non-adipose organs may provide novel strategies for treating obesity-associated disorders. Furthermore, understanding the crosstalk between PLIN proteins and cellular signaling pathways could offer insights into mechanisms underlying lipid homeostasis and energy metabolism.
This review discusses the functional significance of PLIN proteins in lipid storage and LD expansion, their regulatory mechanisms, and their broader implications in metabolic health and disease. By elucidating the role of PLINs in lipid metabolism, researchers can develop targeted therapies to combat metabolic disorders such as obesity, diabetes, and non-alcoholic fatty liver disease.
Keywords: Lipid droplets (LDs); Perilipin proteins (PLIN1–PLIN5); Lipid metabolism regulation; Adipose tissue and lipolysis; Triglyceride
