Lipid droplets are intracellular mechanical stressors that impair hepatocyte function.
Proc Natl Acad Sci U S A
; 120(16): e2216811120, 2023 04 18.
Article
in En
| MEDLINE
| ID: mdl-37036981
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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Carcinoma, Hepatocellular
/
Non-alcoholic Fatty Liver Disease
/
Liver Neoplasms
Type of study:
Prognostic_studies
/
Risk_factors_studies
Limits:
Humans
Language:
En
Journal:
Proc Natl Acad Sci U S A
Year:
2023
Document type:
Article