Relationship between Liver Stiffness and Steatosis in Obesity Conditions: In Vivo and In Vitro Studies
Obesity is a major risk factor for metabolic dysfunction such as non-alcoholic fatty liver disease (NAFLD). The NAFLD spectrum ranges from simple steatosis, to steatohepatitis, fibrosis, and cirrhosis. The aim of this study is to characterize the grade of steatosis being associated with overnutritio...
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MDPI AG
2022-05-01
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author | Francesca Baldini Mohamad Khalil Alice Bartolozzi Massimo Vassalli Agostino Di Ciaula Piero Portincasa Laura Vergani |
author_facet | Francesca Baldini Mohamad Khalil Alice Bartolozzi Massimo Vassalli Agostino Di Ciaula Piero Portincasa Laura Vergani |
author_sort | Francesca Baldini |
collection | DOAJ |
description | Obesity is a major risk factor for metabolic dysfunction such as non-alcoholic fatty liver disease (NAFLD). The NAFLD spectrum ranges from simple steatosis, to steatohepatitis, fibrosis, and cirrhosis. The aim of this study is to characterize the grade of steatosis being associated with overnutrition and obesity, both at the level of single hepatocyte and whole liver, and to correlate it with the hepatocyte/liver stiffness and dysfunction. For the in vivo study, 60 subjects were enrolled and grouped based on the stage of liver steatosis/fibrosis according to biochemical analyses, liver ultrasonography (USG) and acoustic radiation force impulse shear wave elastography (ARFI-SWE). For single hepatocyte analyses we employed in vitro models of moderate and severe steatosis on which to assess the single cell biomechanics by Single Cell Force Spectroscopy (SCFS) and Quantitative Phase Microscopy (QPM). Results show that in vivo liver stiffness depends mainly on the extent of fat accumulation and not on fibrosis. These results parallel the in vitro observations showing that hepatocyte stiffness and dysfunction increase with increasing fat accumulation and lipid droplet enlargement. Our findings indicate that the extent of steatosis markedly affects the biomechanical properties of both liver and single hepatocytes thus proving insights about the role of modulation of liver/hepatocyte elasticity as a physical mechanism transducing the obesity-dependent excess of plasmatic lipids towards liver steatosis and dysfunction. |
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language | English |
last_indexed | 2024-03-10T03:15:35Z |
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series | Biomolecules |
spelling | doaj.art-7244086fab5449f9b3ce08bb76f800a92023-11-23T10:14:48ZengMDPI AGBiomolecules2218-273X2022-05-0112573310.3390/biom12050733Relationship between Liver Stiffness and Steatosis in Obesity Conditions: In Vivo and In Vitro StudiesFrancesca Baldini0Mohamad Khalil1Alice Bartolozzi2Massimo Vassalli3Agostino Di Ciaula4Piero Portincasa5Laura Vergani6Department of Earth, Environment and Life Sciences (DISTAV), University of Genova, Corso Europa 26, 16132 Genova, ItalyClinica Medica “A. Murri”, Department of Biomedical Sciences and Human Oncology, University of Bari Medical School, Piazza Giulio Cesare 11, 70124 Bari, ItalyDipartimento di Ingegneria dell’Informazione, Università degli Studi di Firenze, Via di S. Marta 3, 50139 Firenze, ItalyJames Watt School of Engineering, University of Glasgow, Glasgow G12 8LT, UKClinica Medica “A. Murri”, Department of Biomedical Sciences and Human Oncology, University of Bari Medical School, Piazza Giulio Cesare 11, 70124 Bari, ItalyClinica Medica “A. Murri”, Department of Biomedical Sciences and Human Oncology, University of Bari Medical School, Piazza Giulio Cesare 11, 70124 Bari, ItalyDepartment of Earth, Environment and Life Sciences (DISTAV), University of Genova, Corso Europa 26, 16132 Genova, ItalyObesity is a major risk factor for metabolic dysfunction such as non-alcoholic fatty liver disease (NAFLD). The NAFLD spectrum ranges from simple steatosis, to steatohepatitis, fibrosis, and cirrhosis. The aim of this study is to characterize the grade of steatosis being associated with overnutrition and obesity, both at the level of single hepatocyte and whole liver, and to correlate it with the hepatocyte/liver stiffness and dysfunction. For the in vivo study, 60 subjects were enrolled and grouped based on the stage of liver steatosis/fibrosis according to biochemical analyses, liver ultrasonography (USG) and acoustic radiation force impulse shear wave elastography (ARFI-SWE). For single hepatocyte analyses we employed in vitro models of moderate and severe steatosis on which to assess the single cell biomechanics by Single Cell Force Spectroscopy (SCFS) and Quantitative Phase Microscopy (QPM). Results show that in vivo liver stiffness depends mainly on the extent of fat accumulation and not on fibrosis. These results parallel the in vitro observations showing that hepatocyte stiffness and dysfunction increase with increasing fat accumulation and lipid droplet enlargement. Our findings indicate that the extent of steatosis markedly affects the biomechanical properties of both liver and single hepatocytes thus proving insights about the role of modulation of liver/hepatocyte elasticity as a physical mechanism transducing the obesity-dependent excess of plasmatic lipids towards liver steatosis and dysfunction.https://www.mdpi.com/2218-273X/12/5/733obesitynon-alcoholic fatty liver disease (NAFLD)hepatocyte steatosisliver stiffnesssingle cell biomechanicsultrasonography |
spellingShingle | Francesca Baldini Mohamad Khalil Alice Bartolozzi Massimo Vassalli Agostino Di Ciaula Piero Portincasa Laura Vergani Relationship between Liver Stiffness and Steatosis in Obesity Conditions: In Vivo and In Vitro Studies Biomolecules obesity non-alcoholic fatty liver disease (NAFLD) hepatocyte steatosis liver stiffness single cell biomechanics ultrasonography |
title | Relationship between Liver Stiffness and Steatosis in Obesity Conditions: In Vivo and In Vitro Studies |
title_full | Relationship between Liver Stiffness and Steatosis in Obesity Conditions: In Vivo and In Vitro Studies |
title_fullStr | Relationship between Liver Stiffness and Steatosis in Obesity Conditions: In Vivo and In Vitro Studies |
title_full_unstemmed | Relationship between Liver Stiffness and Steatosis in Obesity Conditions: In Vivo and In Vitro Studies |
title_short | Relationship between Liver Stiffness and Steatosis in Obesity Conditions: In Vivo and In Vitro Studies |
title_sort | relationship between liver stiffness and steatosis in obesity conditions in vivo and in vitro studies |
topic | obesity non-alcoholic fatty liver disease (NAFLD) hepatocyte steatosis liver stiffness single cell biomechanics ultrasonography |
url | https://www.mdpi.com/2218-273X/12/5/733 |
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