The summaries are free for public
use. The Chronic Liver Disease
Foundation will continue to add and
archive summaries of articles deemed
relevant to CLDF by the Board of
Trustees and its Advisors.
Abstract Details
A new perspective on NAFLD: Focusing on lipid droplets
J Hepatol. 2022 Apr;76(4):934-945. doi: 10.1016/j.jhep.2021.11.009.Epub 2021 Nov 15.
1Division of Translational Medicine and Human Genetics, The Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Human Development and Health, Faculty of Medicine, University of Southampton, Southampton, United Kingdom.
2Division of Gastroenterology, University of Washington, Seattle, WA 98195-6424, United States. Electronic address: rmcarr@medicine.washington.edu.
Abstract
Lipid droplets (LDs) are complex and metabolically active organelles. They are composed of a neutral lipid core surrounded by a monolayer of phospholipids and proteins. LD accumulation in hepatocytes is the distinctive characteristic of non-alcoholic fatty liver disease (NAFLD), which is a chronic, heterogeneous liver condition that can progress to liver fibrosis and hepatocellular carcinoma. Though recent research has improved our understanding of the mechanisms linking LD accumulation to NAFLD progression, numerous aspects of LD biology are either poorly understood or unknown. In this review, we provide a description of several key mechanisms that contribute to LD accumulation in hepatocytes, favouring NAFLD progression. First, we highlight the importance of LD architecture and describe how the dysregulation of LD biogenesis leads to endoplasmic reticulum stress and inflammation. This is followed by an analysis of the causal nexus that exists between LD proteome composition and LD degradation. Finally, we describe how the increase in size of LDs causes activation of hepatic stellate cells, leading to liver fibrosis and hepatocellular carcinoma. We conclude that acquiring a more sophisticated understanding of LD biology will provide crucial insights into the heterogeneity of NAFLD and assist in the development of therapeutic approaches for this liver disease.