Fatty Hepatocytes Induce Skeletal Muscle Atrophy In Vitro: A New 3D Platform to Study the Protective Effect of Albumin in Non-Alcoholic Fatty Liver

The liver neutralizes endogenous and exogenous toxins and metabolites, being metabolically interconnected with many organs. Numerous clinical and experimental studies show a strong association between Non-alcoholic fatty liver disease (NAFLD) and loss of skeletal muscle mass known as sarcopenia. Liv...

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Bibliographic Details
Published in:Biomedicines 2022-04, Vol.10 (5), p.958
Main Authors: De Chiara, Francesco, Ferret-Miñana, Ainhoa, Fernández-Costa, Juan M, Senni, Alice, Jalan, Rajiv, Ramón-Azcón, Javier
Format: Article
Language:English
Subjects:
Albumin
ammonia
Apoptosis
Atrophy
Biodegradable materials
Carboxymethylcellulose
Cell culture
Cellulose
crosstalk
Diabetes
Drug development
Experiments
Fatty acids
Fatty liver
Gelatin
Hepatocytes
Hydrogels
Insulin resistance
Lipids
Liver diseases
Liver transplantation
Musculoskeletal system
Myotubes
NEFAs
Obesity
Overweight
Phenotypes
Sarcopenia
Skeletal muscle
Tissue engineering
Transplants & implants
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Summary:The liver neutralizes endogenous and exogenous toxins and metabolites, being metabolically interconnected with many organs. Numerous clinical and experimental studies show a strong association between Non-alcoholic fatty liver disease (NAFLD) and loss of skeletal muscle mass known as sarcopenia. Liver transplantation solves the hepatic-related insufficiencies, but it is unable to revert sarcopenia. Knowing the mechanism(s) by which different organs communicate with each other is crucial to improve the drug development that still relies on the two-dimensional models. However, those models fail to mimic the pathological features of the disease. Here, both liver and skeletal muscle cells were encapsulated in gelatin methacryloyl and carboxymethylcellulose to recreate the disease's phenotype in vitro. The 3D hepatocytes were challenged with non-esterified fatty acids (NEFAs) inducing features of Non-alcoholic fatty liver (NAFL) such as lipid accumulation, metabolic activity impairment and apoptosis. The 3D skeletal muscle tissues incubated with supernatant from fatty hepatocytes displayed loss of maturation and atrophy. This study demonstrates the connection between the liver and the skeletal muscle in NAFL, narrowing down the players for potential treatments. The tool herein presented was employed as a customizable 3D in vitro platform to assess the protective effect of albumin on both hepatocytes and myotubes.
ISSN:2227-9059
2227-9059
DOI:10.3390/biomedicines10050958