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Too Much of a Good Thing? An Evolutionary Theory to Explain the Role of Ceramides in NAFLD

Non-alcoholic fatty liver disease (NAFLD), which ranges from the relatively benign and reversible fatty liver (NAFL) to the more advanced and deadly steatohepatitis (NASH), affects a remarkably high percentage of adults in the population. Depending upon severity, NAFLD can increase one's risk f...

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Autores principales: Poss, Annelise M., Summers, Scott A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7411076/
https://www.ncbi.nlm.nih.gov/pubmed/32849291
http://dx.doi.org/10.3389/fendo.2020.00505
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author Poss, Annelise M.
Summers, Scott A.
author_facet Poss, Annelise M.
Summers, Scott A.
author_sort Poss, Annelise M.
collection PubMed
description Non-alcoholic fatty liver disease (NAFLD), which ranges from the relatively benign and reversible fatty liver (NAFL) to the more advanced and deadly steatohepatitis (NASH), affects a remarkably high percentage of adults in the population. Depending upon severity, NAFLD can increase one's risk for diabetes, cardiovascular disease, and hepatocellular carcinoma. Though the dominant histological feature of all forms of the disease is the accumulation of liver triglycerides, these molecules are likely not pathogenic, but rather serve to protect the liver from the damaging consequences of overnutrition. We propose herein that the less abundant ceramides, through evolutionarily-conserved actions intended to help organisms adapt to nutrient excess, drive the cellular events that define NAFL/NASH. In early stages of the disease process, they promote lipid uptake and storage, whilst inhibiting utilization of glucose. In later stages, they stimulate hepatocyte apoptosis and fibrosis. In rodents, blocking ceramide synthesis ameliorates all stages of NAFLD. In humans, serum and liver ceramides correlate with the severity of NAFLD and its comorbidities diabetes and heart disease. These studies identify key roles for ceramides in these hepatic manifestations of the metabolic syndrome.
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spelling pubmed-74110762020-08-25 Too Much of a Good Thing? An Evolutionary Theory to Explain the Role of Ceramides in NAFLD Poss, Annelise M. Summers, Scott A. Front Endocrinol (Lausanne) Endocrinology Non-alcoholic fatty liver disease (NAFLD), which ranges from the relatively benign and reversible fatty liver (NAFL) to the more advanced and deadly steatohepatitis (NASH), affects a remarkably high percentage of adults in the population. Depending upon severity, NAFLD can increase one's risk for diabetes, cardiovascular disease, and hepatocellular carcinoma. Though the dominant histological feature of all forms of the disease is the accumulation of liver triglycerides, these molecules are likely not pathogenic, but rather serve to protect the liver from the damaging consequences of overnutrition. We propose herein that the less abundant ceramides, through evolutionarily-conserved actions intended to help organisms adapt to nutrient excess, drive the cellular events that define NAFL/NASH. In early stages of the disease process, they promote lipid uptake and storage, whilst inhibiting utilization of glucose. In later stages, they stimulate hepatocyte apoptosis and fibrosis. In rodents, blocking ceramide synthesis ameliorates all stages of NAFLD. In humans, serum and liver ceramides correlate with the severity of NAFLD and its comorbidities diabetes and heart disease. These studies identify key roles for ceramides in these hepatic manifestations of the metabolic syndrome. Frontiers Media S.A. 2020-07-31 /pmc/articles/PMC7411076/ /pubmed/32849291 http://dx.doi.org/10.3389/fendo.2020.00505 Text en Copyright © 2020 Poss and Summers. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Endocrinology
Poss, Annelise M.
Summers, Scott A.
Too Much of a Good Thing? An Evolutionary Theory to Explain the Role of Ceramides in NAFLD
title Too Much of a Good Thing? An Evolutionary Theory to Explain the Role of Ceramides in NAFLD
title_full Too Much of a Good Thing? An Evolutionary Theory to Explain the Role of Ceramides in NAFLD
title_fullStr Too Much of a Good Thing? An Evolutionary Theory to Explain the Role of Ceramides in NAFLD
title_full_unstemmed Too Much of a Good Thing? An Evolutionary Theory to Explain the Role of Ceramides in NAFLD
title_short Too Much of a Good Thing? An Evolutionary Theory to Explain the Role of Ceramides in NAFLD
title_sort too much of a good thing? an evolutionary theory to explain the role of ceramides in nafld
topic Endocrinology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7411076/
https://www.ncbi.nlm.nih.gov/pubmed/32849291
http://dx.doi.org/10.3389/fendo.2020.00505
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