Associations between circulating amino acids and metabolic dysfunction‐associated steatotic liver disease in individuals living with severe obesity

Abstract Metabolic dysfunction‐associated steatotic liver disease (MASLD) describes liver diseases caused by the accumulation of triglycerides in hepatocytes (steatosis) as well as the resulting inflammation and fibrosis. Previous studies have demonstrated that accumulation of fat in visceral adipos...

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Main Authors: Ina Maltais‐Payette, Jérôme Bourgault, Marie‐Frédérique Gauthier, Laurent Biertho, Simon Marceau, François Julien, Patricia L. Mitchell, Christian Couture, Francis Brière, Jacques Corbeil, Benoit J. Arsenault, André Tchernof
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Language:English
Published: Wiley 2025-02-01
Series:Physiological Reports
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Online Access:https://doi.org/10.14814/phy2.70171
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author Ina Maltais‐Payette
Jérôme Bourgault
Marie‐Frédérique Gauthier
Laurent Biertho
Simon Marceau
François Julien
Patricia L. Mitchell
Christian Couture
Francis Brière
Jacques Corbeil
Benoit J. Arsenault
André Tchernof
author_facet Ina Maltais‐Payette
Jérôme Bourgault
Marie‐Frédérique Gauthier
Laurent Biertho
Simon Marceau
François Julien
Patricia L. Mitchell
Christian Couture
Francis Brière
Jacques Corbeil
Benoit J. Arsenault
André Tchernof
author_sort Ina Maltais‐Payette
collection DOAJ
description Abstract Metabolic dysfunction‐associated steatotic liver disease (MASLD) describes liver diseases caused by the accumulation of triglycerides in hepatocytes (steatosis) as well as the resulting inflammation and fibrosis. Previous studies have demonstrated that accumulation of fat in visceral adipose tissue compartments and the liver is associated with alterations in the circulating levels of some amino acids, notably glutamate. This study aimed to investigate the associations between circulating amino acids, particularly glutamate, and MASLD. In addition, we hypothesized that liver steatosis, concomitant with visceral adiposity, could contribute to the association between circulating glutamate and visceral obesity. We studied a sample of 150 patients living with severe obesity who were non‐diabetic and selected to represent a wide range of MASLD severity. Liver histological features were determined by a pathologist from a biopsy sample obtained at the time of bariatric surgery. Bulk RNA sequencing measured the hepatic mRNA expression level of selected genes related to the urea cycle and glutamate metabolism. Fasting plasma amino acid levels were measured by liquid chromatography coupled with tandem mass spectrometry. Patients with more advanced steatosis had larger visceral adipocytes, higher levels of circulating tyrosine, glutamate, and alanine as well as lower levels of serine. MASLD severity was significantly associated with the hepatic mRNA expression of glutamate metabolism genes such as GLS1, GLUL (positively), and NAGS (inversely). In individuals living with obesity, MASLD severity is associated with visceral adipocyte hypertrophy, higher circulating glutamate as well as potential alterations of hepatic amino acid and nitrogen metabolism.
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spelling doaj-art-e86ec986db424dff9c561137a898f7572025-08-20T03:25:12ZengWileyPhysiological Reports2051-817X2025-02-01133n/an/a10.14814/phy2.70171Associations between circulating amino acids and metabolic dysfunction‐associated steatotic liver disease in individuals living with severe obesityIna Maltais‐Payette0Jérôme Bourgault1Marie‐Frédérique Gauthier2Laurent Biertho3Simon Marceau4François Julien5Patricia L. Mitchell6Christian Couture7Francis Brière8Jacques Corbeil9Benoit J. Arsenault10André Tchernof11Quebec Heart and Lung Institute – Laval University Quebec Quebec CanadaQuebec Heart and Lung Institute – Laval University Quebec Quebec CanadaQuebec Heart and Lung Institute – Laval University Quebec Quebec CanadaQuebec Heart and Lung Institute – Laval University Quebec Quebec CanadaQuebec Heart and Lung Institute – Laval University Quebec Quebec CanadaQuebec Heart and Lung Institute – Laval University Quebec Quebec CanadaQuebec Heart and Lung Institute – Laval University Quebec Quebec CanadaQuebec Heart and Lung Institute – Laval University Quebec Quebec CanadaDepartment of Molecular Medicine, Faculty of Medicine Laval University Quebec Quebec CanadaDepartment of Molecular Medicine, Faculty of Medicine Laval University Quebec Quebec CanadaQuebec Heart and Lung Institute – Laval University Quebec Quebec CanadaQuebec Heart and Lung Institute – Laval University Quebec Quebec CanadaAbstract Metabolic dysfunction‐associated steatotic liver disease (MASLD) describes liver diseases caused by the accumulation of triglycerides in hepatocytes (steatosis) as well as the resulting inflammation and fibrosis. Previous studies have demonstrated that accumulation of fat in visceral adipose tissue compartments and the liver is associated with alterations in the circulating levels of some amino acids, notably glutamate. This study aimed to investigate the associations between circulating amino acids, particularly glutamate, and MASLD. In addition, we hypothesized that liver steatosis, concomitant with visceral adiposity, could contribute to the association between circulating glutamate and visceral obesity. We studied a sample of 150 patients living with severe obesity who were non‐diabetic and selected to represent a wide range of MASLD severity. Liver histological features were determined by a pathologist from a biopsy sample obtained at the time of bariatric surgery. Bulk RNA sequencing measured the hepatic mRNA expression level of selected genes related to the urea cycle and glutamate metabolism. Fasting plasma amino acid levels were measured by liquid chromatography coupled with tandem mass spectrometry. Patients with more advanced steatosis had larger visceral adipocytes, higher levels of circulating tyrosine, glutamate, and alanine as well as lower levels of serine. MASLD severity was significantly associated with the hepatic mRNA expression of glutamate metabolism genes such as GLS1, GLUL (positively), and NAGS (inversely). In individuals living with obesity, MASLD severity is associated with visceral adipocyte hypertrophy, higher circulating glutamate as well as potential alterations of hepatic amino acid and nitrogen metabolism.https://doi.org/10.14814/phy2.70171amino acidsmetabolic‐dysfunction associated steatotic liver diseaseobesity
spellingShingle Ina Maltais‐Payette
Jérôme Bourgault
Marie‐Frédérique Gauthier
Laurent Biertho
Simon Marceau
François Julien
Patricia L. Mitchell
Christian Couture
Francis Brière
Jacques Corbeil
Benoit J. Arsenault
André Tchernof
Associations between circulating amino acids and metabolic dysfunction‐associated steatotic liver disease in individuals living with severe obesity
Physiological Reports
amino acids
metabolic‐dysfunction associated steatotic liver disease
obesity
title Associations between circulating amino acids and metabolic dysfunction‐associated steatotic liver disease in individuals living with severe obesity
title_full Associations between circulating amino acids and metabolic dysfunction‐associated steatotic liver disease in individuals living with severe obesity
title_fullStr Associations between circulating amino acids and metabolic dysfunction‐associated steatotic liver disease in individuals living with severe obesity
title_full_unstemmed Associations between circulating amino acids and metabolic dysfunction‐associated steatotic liver disease in individuals living with severe obesity
title_short Associations between circulating amino acids and metabolic dysfunction‐associated steatotic liver disease in individuals living with severe obesity
title_sort associations between circulating amino acids and metabolic dysfunction associated steatotic liver disease in individuals living with severe obesity
topic amino acids
metabolic‐dysfunction associated steatotic liver disease
obesity
url https://doi.org/10.14814/phy2.70171
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