Hepatic lipid droplets: A balancing act between energy storage and metabolic dysfunction in NAFLD
TLDR
The protein and lipid composition of LDs are critical factors in determining the progression from simple steatosis, and defining the detailed molecular mechanisms linking LDs to metabolic dysfunction is important for designing effective therapeutic approaches targeting NAFLD and its comorbidities.Abstract:
Background Non-alcoholic fatty liver disease (NAFLD) is defined by the abundance of lipid droplets (LDs) in hepatocytes. While historically considered simply depots for energy storage, LDs are increasingly recognized to impact a wide range of biological processes that influence cellular metabolism, signaling, and function. While progress has been made toward understanding the factors leading to LD accumulation (i.e. steatosis) and its progression to advanced stages of NAFLD and/or systemic metabolic dysfunction, much remains to be resolved. Scope of review This review covers many facets of LD biology. We provide a brief overview of the major pathways of lipid accretion and degradation that contribute to steatosis and how they are altered in NAFLD. The major focus is on the relationship between LDs and cell function and the detailed mechanisms that couple or uncouple steatosis from the severity and progression of NAFLD and systemic comorbidities. The importance of specific lipids and proteins within or on LDs as key components that determine whether LD accumulation is linked to cellular and metabolic dysfunction is presented. We discuss emerging areas of LD biology and future research directions that are needed to advance our understanding of the role of LDs in NAFLD etiology. Major conclusions Impairments in LD breakdown appear to contribute to disease progression, but inefficient incorporation of fatty acids (FAs) into LD-containing triacylglycerol (TAG) and the consequential changes in FA partitioning also affect NAFLD etiology. Increased LD abundance in hepatocytes does not necessarily equate to cellular dysfunction. While LD accumulation is the prerequisite step for most NAFLD cases, the protein and lipid composition of LDs are critical factors in determining the progression from simple steatosis. Further defining the detailed molecular mechanisms linking LDs to metabolic dysfunction is important for designing effective therapeutic approaches targeting NAFLD and its comorbidities.read more
Citations
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Journal ArticleDOI
A new perspective on NAFLD: focusing on lipid droplets.
TL;DR: In this article, the authors provide a description of several key mechanisms that contribute to LDs accumulation in the hepatocytes, favouring NAFLD progression, and highlight the importance of LD architecture and describe how the dysregulation of LD biogenesis leads to endoplasmic reticulum stress and inflammation.
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Panu K. Luukkonen,Auli Nick,Maarit Hölttä-Vuori,Christoph Thiele,Elina Isokuortti,Susanna Lallukka-Brück,You Zhou,Antti Hakkarainen,Nina Lundbom,Markku Peltonen,Marju Orho-Melander,Matej Orešič,Tuulia Hyötyläinen,Leanne Hodson,Elina Ikonen,Hannele Yki-Javinen +15 more
TL;DR: In this article, the authors compared the handling of labeled polyunsaturated fatty acids (PUFAs) and saturated fatty acid (SFA) in vivo in humans and in cells harboring different PNPLA3 genotypes.
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Plasma Free Fatty Acid Concentration as a Modifiable Risk Factor for Metabolic Disease.
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Hepatic sexual dimorphism - implications for non-alcoholic fatty liver disease.
Philippe Lefebvre,Bart Staels +1 more
TL;DR: In this article, the accumulating evidence of sexual dimorphism in NAFLD was discussed, which is currently rarely considered in preclinical and clinical studies and could lead to improved understanding of the biological processes that are dysregulated in non-alcoholic fatty liver disease, to the identification of relevant therapeutic targets and to improved risk stratification of patients undergoing therapeutic intervention.
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Exercise improves lipid droplet metabolism disorder through activation of AMPK-mediated lipophagy in NAFLD.
Hui Li,Yaoshan Dun,Wenliang Zhang,Baiyang You,Yuan Liu,Siqian Fu,Ling Qiu,Jing Cheng,Jeffrey W. Ripley-Gonzalez,Suixin Liu +9 more
TL;DR: In this article, the effect of exercise on lipid droplet (LD) metabolism disorder in nonalcoholic fatty liver disease (NAFLD) was investigated in C57BL/6J mice.
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