"Lipid droplets are intracellular mechanical stressors that impair hepa" by Abigail E. Loneker, Farid Alisafaei et al.
 

Lipid droplets are intracellular mechanical stressors that impair hepatocyte function

Document Type

Article

Publication Date

4-18-2023

Abstract

Matrix stiffening and external mechanical stress have been linked to disease and cancer development in multiple tissues, including the liver, where cirrhosis (which increases stiffness markedly) is the major risk factor for hepatocellular carcinoma. Patients with nonalcoholic fatty liver disease and lipid droplet-filled hepatocytes, however, can develop cancer in noncirrhotic, relatively soft tissue. Here, by treating primary human hepatocytes with the monounsaturated fatty acid oleate, we show that lipid droplets are intracellular mechanical stressors with similar effects to tissue stiffening, including nuclear deformation, chromatin condensation, and impaired hepatocyte function. Mathematical modeling of lipid droplets as inclusions that have only mechanical interactions with other cellular components generated results consistent with our experiments. These data show that lipid droplets are intracellular sources of mechanical stress and suggest that nuclear membrane tension integrates cell responses to combined internal and external stresses.

Identifier

85152095971 (Scopus)

Publication Title

Proceedings of the National Academy of Sciences of the United States of America

External Full Text Location

https://doi.org/10.1073/pnas.2216811120

e-ISSN

10916490

ISSN

00278424

PubMed ID

37036981

Issue

16

Volume

120

Grant

15-48571

Fund Ref

National Science Foundation

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