Lipid droplets in steatotic liver disease

Abstract

Purpose of review This review aims to discuss the most recent evidence exploring the role of lipid droplets in steatotic liver disease (SLD). We highlight the breadth of mechanisms by which lipid droplets may contribute to the progression of SLD with a particular focus on the role of lipid droplets as inducers of mechanical stress within hepatocytes and genetic mutations in lipid droplet associated proteins. Finally, this review provides an update on clinical trials exploring the therapeutic potential and strategies targeting lipid droplets. Recent findings The size, composition and location of hepatic lipid droplets strongly influence the pathological role of these organelles in SLD. Emerging studies are beginning to elucidate the importance of lipid droplet induced hepatocyte mechanical stress. Novel strategies targeting lipid droplets, including the effects of lipid droplet associated protein mutations, show promising therapeutic potential. Summary Much more than a histological feature, lipid droplets are complex heterogenous organelles crucial to cellular metabolism with important causative roles in the development and progression of SLD. Lipid droplet induced mechanical stress may exacerbate hepatic inflammation and fibrogenesis and potentially contribute to the development of a pro-carcinogenic hepatic environment. The integration of advancements in genetics and molecular biology in upcoming treatments aspires to transcend symptomatic alleviation and address the fundamental causes and pathological development of SLD.

Editorial: Quantitative and qualitative aspects of lipids and lipoproteins in health and disease: nutrition, physiology and genetics

“…Lipid droplets are essentially organelles, with recent research indicating that they have a high level of complexity. Scorletti and Bilson [2] provide a stateof-the-art overview of the biology of hepatic lipid droplets covering their biogenesis and degradation, including the role of genetic factors; role in steatotic liver disease pathogenesis and progression; and potential as therapeutic targets. Lipid droplets act as intracellular mechanical stressors so contributing to hepatocyte dysfunction and progression of steatotic liver disease [3].…”