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Resistance to Diet-Induced Obesity and Associated Metabolic Perturbations in Haploinsufficient Monocarboxylate Transporter 1 Mice

The monocarboxylate transporter 1 (MCT1 or SLC16A1) is a carrier of short-chain fatty acids, ketone bodies, and lactate in several tissues. Genetically modified C57BL/6J mice were produced by targeted disruption of the mct1 gene in order to understand the role of this transporter in energy homeostas...

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Autores principales: Lengacher, Sylvain, Nehiri-Sitayeb, Touria, Steiner, Nadia, Carneiro, Lionel, Favrod, Céline, Preitner, Frédéric, Thorens, Bernard, Stehle, Jean-Christophe, Dix, Laure, Pralong, François, Magistretti, Pierre J., Pellerin, Luc
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3867350/
https://www.ncbi.nlm.nih.gov/pubmed/24367518
http://dx.doi.org/10.1371/journal.pone.0082505
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author Lengacher, Sylvain
Nehiri-Sitayeb, Touria
Steiner, Nadia
Carneiro, Lionel
Favrod, Céline
Preitner, Frédéric
Thorens, Bernard
Stehle, Jean-Christophe
Dix, Laure
Pralong, François
Magistretti, Pierre J.
Pellerin, Luc
author_facet Lengacher, Sylvain
Nehiri-Sitayeb, Touria
Steiner, Nadia
Carneiro, Lionel
Favrod, Céline
Preitner, Frédéric
Thorens, Bernard
Stehle, Jean-Christophe
Dix, Laure
Pralong, François
Magistretti, Pierre J.
Pellerin, Luc
author_sort Lengacher, Sylvain
collection PubMed
description The monocarboxylate transporter 1 (MCT1 or SLC16A1) is a carrier of short-chain fatty acids, ketone bodies, and lactate in several tissues. Genetically modified C57BL/6J mice were produced by targeted disruption of the mct1 gene in order to understand the role of this transporter in energy homeostasis. Null mutation was embryonically lethal, but MCT1 (+/−) mice developed normally. However, when fed high fat diet (HFD), MCT1 (+/−) mice displayed resistance to development of diet-induced obesity (24.8% lower body weight after 16 weeks of HFD), as well as less insulin resistance and no hepatic steatosis as compared to littermate MCT1 (+/+) mice used as controls. Body composition analysis revealed that reduced weight gain in MCT1 (+/−) mice was due to decreased fat accumulation (50.0% less after 9 months of HFD) notably in liver and white adipose tissue. This phenotype was associated with reduced food intake under HFD (12.3% less over 10 weeks) and decreased intestinal energy absorption (9.6% higher stool energy content). Indirect calorimetry measurements showed ∼ 15% increase in O(2) consumption and CO(2) production during the resting phase, without any changes in physical activity. Determination of plasma concentrations for various metabolites and hormones did not reveal significant changes in lactate and ketone bodies levels between the two genotypes, but both insulin and leptin levels, which were elevated in MCT1 (+/+) mice when fed HFD, were reduced in MCT1 (+/−) mice under HFD. Interestingly, the enhancement in expression of several genes involved in lipid metabolism in the liver of MCT1 (+/+) mice under high fat diet was prevented in the liver of MCT1 (+/−) mice under the same diet, thus likely contributing to the observed phenotype. These findings uncover the critical role of MCT1 in the regulation of energy balance when animals are exposed to an obesogenic diet.
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spelling pubmed-38673502013-12-23 Resistance to Diet-Induced Obesity and Associated Metabolic Perturbations in Haploinsufficient Monocarboxylate Transporter 1 Mice Lengacher, Sylvain Nehiri-Sitayeb, Touria Steiner, Nadia Carneiro, Lionel Favrod, Céline Preitner, Frédéric Thorens, Bernard Stehle, Jean-Christophe Dix, Laure Pralong, François Magistretti, Pierre J. Pellerin, Luc PLoS One Research Article The monocarboxylate transporter 1 (MCT1 or SLC16A1) is a carrier of short-chain fatty acids, ketone bodies, and lactate in several tissues. Genetically modified C57BL/6J mice were produced by targeted disruption of the mct1 gene in order to understand the role of this transporter in energy homeostasis. Null mutation was embryonically lethal, but MCT1 (+/−) mice developed normally. However, when fed high fat diet (HFD), MCT1 (+/−) mice displayed resistance to development of diet-induced obesity (24.8% lower body weight after 16 weeks of HFD), as well as less insulin resistance and no hepatic steatosis as compared to littermate MCT1 (+/+) mice used as controls. Body composition analysis revealed that reduced weight gain in MCT1 (+/−) mice was due to decreased fat accumulation (50.0% less after 9 months of HFD) notably in liver and white adipose tissue. This phenotype was associated with reduced food intake under HFD (12.3% less over 10 weeks) and decreased intestinal energy absorption (9.6% higher stool energy content). Indirect calorimetry measurements showed ∼ 15% increase in O(2) consumption and CO(2) production during the resting phase, without any changes in physical activity. Determination of plasma concentrations for various metabolites and hormones did not reveal significant changes in lactate and ketone bodies levels between the two genotypes, but both insulin and leptin levels, which were elevated in MCT1 (+/+) mice when fed HFD, were reduced in MCT1 (+/−) mice under HFD. Interestingly, the enhancement in expression of several genes involved in lipid metabolism in the liver of MCT1 (+/+) mice under high fat diet was prevented in the liver of MCT1 (+/−) mice under the same diet, thus likely contributing to the observed phenotype. These findings uncover the critical role of MCT1 in the regulation of energy balance when animals are exposed to an obesogenic diet. Public Library of Science 2013-12-18 /pmc/articles/PMC3867350/ /pubmed/24367518 http://dx.doi.org/10.1371/journal.pone.0082505 Text en © 2013 Lengacher 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
Lengacher, Sylvain
Nehiri-Sitayeb, Touria
Steiner, Nadia
Carneiro, Lionel
Favrod, Céline
Preitner, Frédéric
Thorens, Bernard
Stehle, Jean-Christophe
Dix, Laure
Pralong, François
Magistretti, Pierre J.
Pellerin, Luc
Resistance to Diet-Induced Obesity and Associated Metabolic Perturbations in Haploinsufficient Monocarboxylate Transporter 1 Mice
title Resistance to Diet-Induced Obesity and Associated Metabolic Perturbations in Haploinsufficient Monocarboxylate Transporter 1 Mice
title_full Resistance to Diet-Induced Obesity and Associated Metabolic Perturbations in Haploinsufficient Monocarboxylate Transporter 1 Mice
title_fullStr Resistance to Diet-Induced Obesity and Associated Metabolic Perturbations in Haploinsufficient Monocarboxylate Transporter 1 Mice
title_full_unstemmed Resistance to Diet-Induced Obesity and Associated Metabolic Perturbations in Haploinsufficient Monocarboxylate Transporter 1 Mice
title_short Resistance to Diet-Induced Obesity and Associated Metabolic Perturbations in Haploinsufficient Monocarboxylate Transporter 1 Mice
title_sort resistance to diet-induced obesity and associated metabolic perturbations in haploinsufficient monocarboxylate transporter 1 mice
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3867350/
https://www.ncbi.nlm.nih.gov/pubmed/24367518
http://dx.doi.org/10.1371/journal.pone.0082505
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