Cargando…

Liver and Muscle in Morbid Obesity: The Interplay of Fatty Liver and Insulin Resistance

INTRODUCTION: Nonalcoholic fatty liver disease (NAFLD) can be seen as a manifestation of overnutrition. The muscle is a central player in the adaptation to energy overload, and there is an association between fatty-muscle and -liver. We aimed to correlate muscle morphology, mitochondrial function an...

Descripción completa

Detalles Bibliográficos
Autores principales: Machado, Mariana Verdelho, Ferreira, Duarte M. S., Castro, Rui E., Silvestre, Ana Rita, Evangelista, Teresinha, Coutinho, João, Carepa, Fátima, Costa, Adília, Rodrigues, Cecília M. P., Cortez-Pinto, Helena
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3281005/
https://www.ncbi.nlm.nih.gov/pubmed/22359625
http://dx.doi.org/10.1371/journal.pone.0031738
_version_ 1782223898672103424
author Machado, Mariana Verdelho
Ferreira, Duarte M. S.
Castro, Rui E.
Silvestre, Ana Rita
Evangelista, Teresinha
Coutinho, João
Carepa, Fátima
Costa, Adília
Rodrigues, Cecília M. P.
Cortez-Pinto, Helena
author_facet Machado, Mariana Verdelho
Ferreira, Duarte M. S.
Castro, Rui E.
Silvestre, Ana Rita
Evangelista, Teresinha
Coutinho, João
Carepa, Fátima
Costa, Adília
Rodrigues, Cecília M. P.
Cortez-Pinto, Helena
author_sort Machado, Mariana Verdelho
collection PubMed
description INTRODUCTION: Nonalcoholic fatty liver disease (NAFLD) can be seen as a manifestation of overnutrition. The muscle is a central player in the adaptation to energy overload, and there is an association between fatty-muscle and -liver. We aimed to correlate muscle morphology, mitochondrial function and insulin signaling with NAFLD severity in morbid obese patients. METHODS: Liver and deltoid muscle biopsies were collected during bariatric surgery in NAFLD patients. NAFLD Activity Score and Younossi's classification for nonalcoholic steatohepatitis (NASH) were applied to liver histology. Muscle evaluation included morphology studies, respiratory chain complex I to IV enzyme assays, and analysis of the insulin signaling cascade. A healthy lean control group was included for muscle morphology and mitochondrial function analyses. RESULTS: Fifty one NAFLD patients were included of whom 43% had NASH. Intramyocellular lipids (IMCL) were associated with the presence of NASH (OR 12.5, p<0.001), progressive hepatic inflammation (p = 0.029) and fibrosis severity (p = 0.010). There was a trend to an association between IMCL and decreased Akt phosphorylation (p = 0.059), despite no association with insulin resistance. In turn, hepatic steatosis (p = 0.015) and inflammation (p = 0.013) were associated with decreased Akt phosphoryation. Citrate synthase activity was lower in obese patients (p = 0.047) whereas complex I (p = 0.040) and III (p = 0.036) activities were higher, compared with controls. Finally, in obese patients, complex I activity increased with progressive steatosis (p = 0.049) and with a trend with fibrosis severity (p = 0.056). CONCLUSIONS: In morbid obese patients, presence of IMCL associates with NASH and advanced fibrosis. Muscle mitochondrial dysfunction does not appear to be a major driving force contributing to muscle fat accumulation, insulin resistance or liver disease. Importantly, insulin resistance in muscle might occur at a late point in the insulin signaling cascade and be associated with IMCL and NAFLD severity.
format Online
Article
Text
id pubmed-3281005
institution National Center for Biotechnology Information
language English
publishDate 2012
publisher Public Library of Science
record_format MEDLINE/PubMed
spelling pubmed-32810052012-02-22 Liver and Muscle in Morbid Obesity: The Interplay of Fatty Liver and Insulin Resistance Machado, Mariana Verdelho Ferreira, Duarte M. S. Castro, Rui E. Silvestre, Ana Rita Evangelista, Teresinha Coutinho, João Carepa, Fátima Costa, Adília Rodrigues, Cecília M. P. Cortez-Pinto, Helena PLoS One Research Article INTRODUCTION: Nonalcoholic fatty liver disease (NAFLD) can be seen as a manifestation of overnutrition. The muscle is a central player in the adaptation to energy overload, and there is an association between fatty-muscle and -liver. We aimed to correlate muscle morphology, mitochondrial function and insulin signaling with NAFLD severity in morbid obese patients. METHODS: Liver and deltoid muscle biopsies were collected during bariatric surgery in NAFLD patients. NAFLD Activity Score and Younossi's classification for nonalcoholic steatohepatitis (NASH) were applied to liver histology. Muscle evaluation included morphology studies, respiratory chain complex I to IV enzyme assays, and analysis of the insulin signaling cascade. A healthy lean control group was included for muscle morphology and mitochondrial function analyses. RESULTS: Fifty one NAFLD patients were included of whom 43% had NASH. Intramyocellular lipids (IMCL) were associated with the presence of NASH (OR 12.5, p<0.001), progressive hepatic inflammation (p = 0.029) and fibrosis severity (p = 0.010). There was a trend to an association between IMCL and decreased Akt phosphorylation (p = 0.059), despite no association with insulin resistance. In turn, hepatic steatosis (p = 0.015) and inflammation (p = 0.013) were associated with decreased Akt phosphoryation. Citrate synthase activity was lower in obese patients (p = 0.047) whereas complex I (p = 0.040) and III (p = 0.036) activities were higher, compared with controls. Finally, in obese patients, complex I activity increased with progressive steatosis (p = 0.049) and with a trend with fibrosis severity (p = 0.056). CONCLUSIONS: In morbid obese patients, presence of IMCL associates with NASH and advanced fibrosis. Muscle mitochondrial dysfunction does not appear to be a major driving force contributing to muscle fat accumulation, insulin resistance or liver disease. Importantly, insulin resistance in muscle might occur at a late point in the insulin signaling cascade and be associated with IMCL and NAFLD severity. Public Library of Science 2012-02-16 /pmc/articles/PMC3281005/ /pubmed/22359625 http://dx.doi.org/10.1371/journal.pone.0031738 Text en Machado et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Machado, Mariana Verdelho
Ferreira, Duarte M. S.
Castro, Rui E.
Silvestre, Ana Rita
Evangelista, Teresinha
Coutinho, João
Carepa, Fátima
Costa, Adília
Rodrigues, Cecília M. P.
Cortez-Pinto, Helena
Liver and Muscle in Morbid Obesity: The Interplay of Fatty Liver and Insulin Resistance
title Liver and Muscle in Morbid Obesity: The Interplay of Fatty Liver and Insulin Resistance
title_full Liver and Muscle in Morbid Obesity: The Interplay of Fatty Liver and Insulin Resistance
title_fullStr Liver and Muscle in Morbid Obesity: The Interplay of Fatty Liver and Insulin Resistance
title_full_unstemmed Liver and Muscle in Morbid Obesity: The Interplay of Fatty Liver and Insulin Resistance
title_short Liver and Muscle in Morbid Obesity: The Interplay of Fatty Liver and Insulin Resistance
title_sort liver and muscle in morbid obesity: the interplay of fatty liver and insulin resistance
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3281005/
https://www.ncbi.nlm.nih.gov/pubmed/22359625
http://dx.doi.org/10.1371/journal.pone.0031738
work_keys_str_mv AT machadomarianaverdelho liverandmuscleinmorbidobesitytheinterplayoffattyliverandinsulinresistance
AT ferreiraduartems liverandmuscleinmorbidobesitytheinterplayoffattyliverandinsulinresistance
AT castroruie liverandmuscleinmorbidobesitytheinterplayoffattyliverandinsulinresistance
AT silvestreanarita liverandmuscleinmorbidobesitytheinterplayoffattyliverandinsulinresistance
AT evangelistateresinha liverandmuscleinmorbidobesitytheinterplayoffattyliverandinsulinresistance
AT coutinhojoao liverandmuscleinmorbidobesitytheinterplayoffattyliverandinsulinresistance
AT carepafatima liverandmuscleinmorbidobesitytheinterplayoffattyliverandinsulinresistance
AT costaadilia liverandmuscleinmorbidobesitytheinterplayoffattyliverandinsulinresistance
AT rodriguesceciliamp liverandmuscleinmorbidobesitytheinterplayoffattyliverandinsulinresistance
AT cortezpintohelena liverandmuscleinmorbidobesitytheinterplayoffattyliverandinsulinresistance