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Lipid droplets and liver disease: from basic biology to clinical implications

Nature Reviews Gastroenterology & Hepatology volume 14, pages 343–355 (2017)Cite this article

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Key Points

  • Depending on the body's needs, the liver utilizes lipids to generate metabolic energy, secretes them as lipoproteins, or packages them for storage

  • Unbalanced lipid storage and utilization result in supraphysiological triglyceride accumulation in hepatocytes, known as hepatic steatosis

  • Hepatic lipids accumulate in organelles known as cytoplasmic lipid droplets

  • Our expanding knowledge of lipid droplets and their associated protein machinery provide opportunities for molecular-based approaches for treating nonalcoholic steatosis and steatohepatitis

Abstract

Lipid droplets are dynamic organelles that store neutral lipids during times of energy excess and serve as an energy reservoir during deprivation. Many prevalent metabolic diseases, such as the metabolic syndrome or obesity, often result in abnormal lipid accumulation in lipid droplets in the liver, also called hepatic steatosis. Obesity-related steatosis, or NAFLD in particular, is a major public health concern worldwide and is frequently associated with insulin resistance and type 2 diabetes mellitus. Here, we review the latest insights into the biology of lipid droplets and their role in maintaining lipid homeostasis in the liver. We also offer a perspective of liver diseases that feature lipid accumulation in these lipid storage organelles, which include NAFLD and viral hepatitis. Although clinical applications of this knowledge are just beginning, we highlight new opportunities for identifying molecular targets for treating hepatic steatosis and steatohepatitis.

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Figure 1: Hepatic steatosis results from an imbalance in lipid storage and lipolysis or secretion.
Figure 2: Histopathology of NAFLD showing areas of macrosteatosis and microsteatosis.
Figure 3: Lipid droplet formation and expansion.
Figure 4: Giant lipid droplet formation.
Figure 5: Lipid droplet consumption.
Figure 6: Possible therapeutic targets to decrease hepatic steatosis.

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Change history

  • 26 April 2017

    In the version of this article initially published online, a line in the legend of Figure 3 incorrectly referred to DGAT1 instead of DGAT2 protein. This error has been corrected for the print, HTML and PDF versions of the article.

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Acknowledgements

We thank S. Alexandrescu for the pathology images in Figure 2, and G. Howard for editorial assistance. R.V.F. acknowledges support from NIH National Institute of General Medical Sciences R01 GM099844, NIH National Institute of Diabetes and Digestive and Kidney Diseases R01 DK056084 and R01 DK101579. T.C.W. acknowledges support from NIH National Institute of General Medical Sciences R01 GM097194. T.C.W. is an investigator of the Howard Hughes Medical Institute. M.B. is supported by a fellowship from the Jane Coffin Childs Foundation.

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Author notes

  1. Nina L. Gluchowski and Michel Becuwe: These authors contributed equally to this work.

  2. Tobias C. Walther and Robert V. Farese: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Genetics and Complex Diseases, Harvard T. H. Chan School of Public Health, 655 Huntington Avenue, Boston, 02115, Massachusetts, USA

    Nina L. Gluchowski, Michel Becuwe, Tobias C. Walther & Robert V. Farese Jr

  2. Boston Children's Hospital Department of Gastroenterology, Hepatology and Nutrition, 300 Longwood Avenue, Boston, 02115, Massachusetts, USA

    Nina L. Gluchowski

  3. Department of Cell Biology, Harvard Medical School, 240 Longwood Avenue, Boston, 02115, Massachusetts, USA

    Tobias C. Walther & Robert V. Farese Jr

  4. Department of Genetics, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, 02115, Massachusetts, USA

    Tobias C. Walther & Robert V. Farese Jr

  5. Department of Genetics and Complex Diseases, Howard Hughes Medical Institute, Harvard T. H. Chan School of Public Health, 655 Huntington Avenue, Boston, 02115, Massachusetts, USA

    Tobias C. Walther

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Gluchowski, N., Becuwe, M., Walther, T. et al. Lipid droplets and liver disease: from basic biology to clinical implications. Nat Rev Gastroenterol Hepatol 14, 343–355 (2017). https://doi.org/10.1038/nrgastro.2017.32

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