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Prolonged fasting-induced metabolic signatures in human skeletal muscle of lean and obese men

Insulin resistance is a well-known physiological adaptation to prolonged fasting in healthy skeletal muscle. Obesity is associated with insulin resistance and metabolic inflexibility in skeletal muscle, and a pronounced increase in the risk of metabolic complications. Under the hypothesis that the m...

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Autores principales: Bak, Ann Mosegaard, Vendelbo, Mikkel Holm, Christensen, Britt, Viggers, Rikke, Bibby, Bo Martin, Rungby, Jørgen, Jørgensen, Jens Otto Lunde, Møller, Niels, Jessen, Niels
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6124727/
https://www.ncbi.nlm.nih.gov/pubmed/30183740
http://dx.doi.org/10.1371/journal.pone.0200817
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author Bak, Ann Mosegaard
Vendelbo, Mikkel Holm
Christensen, Britt
Viggers, Rikke
Bibby, Bo Martin
Rungby, Jørgen
Jørgensen, Jens Otto Lunde
Møller, Niels
Jessen, Niels
author_facet Bak, Ann Mosegaard
Vendelbo, Mikkel Holm
Christensen, Britt
Viggers, Rikke
Bibby, Bo Martin
Rungby, Jørgen
Jørgensen, Jens Otto Lunde
Møller, Niels
Jessen, Niels
author_sort Bak, Ann Mosegaard
collection PubMed
description Insulin resistance is a well-known physiological adaptation to prolonged fasting in healthy skeletal muscle. Obesity is associated with insulin resistance and metabolic inflexibility in skeletal muscle, and a pronounced increase in the risk of metabolic complications. Under the hypothesis that the metabolic traits of insulin resistance associated with prolonged fasting are different from insulin resistance associated with obesity, we examined nine obese and nine lean participants during 12 and 72h of fasting, respectively. Insulin resistance in obese participants was associated with impaired insulin signaling, and reduced levels of glucose-6-phosphate and TCA-cycle intermediates. 72h of fasting in lean participants reduced insulin-stimulated glucose uptake to levels similar to obese participants fasted for 12h. This was associated with increased lipid oxidation, but not accumulation of diacylglycerol or acylcarnitines and impairment of insulin signaling. Prolonged fasting was associated with pronounced increases in β-hydroxybutyrate and β- hydroxybutyrylcarnitine levels in skeletal muscle suggesting augmented ketone body metabolism. Fasting induced insulin resistance may be a consequence of substrate competition. The underlying mechanism behind insulin resistance in obesity is thus not comparable to the physiological adaptations in skeletal muscle induced by prolonged fasting in lean participants.
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spelling pubmed-61247272018-09-16 Prolonged fasting-induced metabolic signatures in human skeletal muscle of lean and obese men Bak, Ann Mosegaard Vendelbo, Mikkel Holm Christensen, Britt Viggers, Rikke Bibby, Bo Martin Rungby, Jørgen Jørgensen, Jens Otto Lunde Møller, Niels Jessen, Niels PLoS One Research Article Insulin resistance is a well-known physiological adaptation to prolonged fasting in healthy skeletal muscle. Obesity is associated with insulin resistance and metabolic inflexibility in skeletal muscle, and a pronounced increase in the risk of metabolic complications. Under the hypothesis that the metabolic traits of insulin resistance associated with prolonged fasting are different from insulin resistance associated with obesity, we examined nine obese and nine lean participants during 12 and 72h of fasting, respectively. Insulin resistance in obese participants was associated with impaired insulin signaling, and reduced levels of glucose-6-phosphate and TCA-cycle intermediates. 72h of fasting in lean participants reduced insulin-stimulated glucose uptake to levels similar to obese participants fasted for 12h. This was associated with increased lipid oxidation, but not accumulation of diacylglycerol or acylcarnitines and impairment of insulin signaling. Prolonged fasting was associated with pronounced increases in β-hydroxybutyrate and β- hydroxybutyrylcarnitine levels in skeletal muscle suggesting augmented ketone body metabolism. Fasting induced insulin resistance may be a consequence of substrate competition. The underlying mechanism behind insulin resistance in obesity is thus not comparable to the physiological adaptations in skeletal muscle induced by prolonged fasting in lean participants. Public Library of Science 2018-09-05 /pmc/articles/PMC6124727/ /pubmed/30183740 http://dx.doi.org/10.1371/journal.pone.0200817 Text en © 2018 Bak 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 (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Bak, Ann Mosegaard
Vendelbo, Mikkel Holm
Christensen, Britt
Viggers, Rikke
Bibby, Bo Martin
Rungby, Jørgen
Jørgensen, Jens Otto Lunde
Møller, Niels
Jessen, Niels
Prolonged fasting-induced metabolic signatures in human skeletal muscle of lean and obese men
title Prolonged fasting-induced metabolic signatures in human skeletal muscle of lean and obese men
title_full Prolonged fasting-induced metabolic signatures in human skeletal muscle of lean and obese men
title_fullStr Prolonged fasting-induced metabolic signatures in human skeletal muscle of lean and obese men
title_full_unstemmed Prolonged fasting-induced metabolic signatures in human skeletal muscle of lean and obese men
title_short Prolonged fasting-induced metabolic signatures in human skeletal muscle of lean and obese men
title_sort prolonged fasting-induced metabolic signatures in human skeletal muscle of lean and obese men
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6124727/
https://www.ncbi.nlm.nih.gov/pubmed/30183740
http://dx.doi.org/10.1371/journal.pone.0200817
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