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Leptin Is Required for Glucose Homeostasis after Roux-en-Y Gastric Bypass in Mice

BACKGROUND & AIMS: Leptin, the protein product of the ob gene, increases energy expenditure and reduces food intake, thereby promoting weight reduction. Leptin also regulates glucose homeostasis and hepatic insulin sensitivity via hypothalamic proopiomelanocortin neurons in mice. Roux-en-Y gastr...

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Autores principales: Mokadem, Mohamad, Zechner, Juliet F., Uchida, Aki, Aguirre, Vincent
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4596552/
https://www.ncbi.nlm.nih.gov/pubmed/26445459
http://dx.doi.org/10.1371/journal.pone.0139960
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author Mokadem, Mohamad
Zechner, Juliet F.
Uchida, Aki
Aguirre, Vincent
author_facet Mokadem, Mohamad
Zechner, Juliet F.
Uchida, Aki
Aguirre, Vincent
author_sort Mokadem, Mohamad
collection PubMed
description BACKGROUND & AIMS: Leptin, the protein product of the ob gene, increases energy expenditure and reduces food intake, thereby promoting weight reduction. Leptin also regulates glucose homeostasis and hepatic insulin sensitivity via hypothalamic proopiomelanocortin neurons in mice. Roux-en-Y gastric bypass (RYGB) induces weight loss that is substantial and sustained despite reducing plasma leptin levels. In addition, patients who fail to undergo diabetes remission after RYGB are hypoletinemic compared to those who do and to lean controls. We have previously demonstrated that the beneficial effects of RYGB in mice require the melanocortin-4 receptor, a downstream effector of leptin action. Based on these observations, we hypothesized that leptin is required for sustained weight reduction and improved glucose homeostasis observed after RYGB. METHODS: To investigate this hypothesis, we performed RYGB or sham operations on leptin-deficient ob/ob mice maintained on regular chow. To investigate whether leptin is involved in post-RYGB weight maintenance, we challenged post-surgical mice with high fat diet. RESULTS: RYGB reduced total body weight, fat and lean mass and caused reduction in calorie intake in ob/ob mice. However, it failed to improve glucose tolerance, glucose-stimulated plasma insulin, insulin tolerance, and fasting plasma insulin. High fat diet eliminated the reduction in calorie intake observed after RYGB in ob/ob mice and promoted weight regain, although not to the same extent as in sham-operated mice. We conclude that leptin is required for the effects of RYGB on glucose homeostasis but not body weight or composition in mice. Our data also suggest that leptin may play a role in post-RYGB weight maintenance.
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spelling pubmed-45965522015-10-20 Leptin Is Required for Glucose Homeostasis after Roux-en-Y Gastric Bypass in Mice Mokadem, Mohamad Zechner, Juliet F. Uchida, Aki Aguirre, Vincent PLoS One Research Article BACKGROUND & AIMS: Leptin, the protein product of the ob gene, increases energy expenditure and reduces food intake, thereby promoting weight reduction. Leptin also regulates glucose homeostasis and hepatic insulin sensitivity via hypothalamic proopiomelanocortin neurons in mice. Roux-en-Y gastric bypass (RYGB) induces weight loss that is substantial and sustained despite reducing plasma leptin levels. In addition, patients who fail to undergo diabetes remission after RYGB are hypoletinemic compared to those who do and to lean controls. We have previously demonstrated that the beneficial effects of RYGB in mice require the melanocortin-4 receptor, a downstream effector of leptin action. Based on these observations, we hypothesized that leptin is required for sustained weight reduction and improved glucose homeostasis observed after RYGB. METHODS: To investigate this hypothesis, we performed RYGB or sham operations on leptin-deficient ob/ob mice maintained on regular chow. To investigate whether leptin is involved in post-RYGB weight maintenance, we challenged post-surgical mice with high fat diet. RESULTS: RYGB reduced total body weight, fat and lean mass and caused reduction in calorie intake in ob/ob mice. However, it failed to improve glucose tolerance, glucose-stimulated plasma insulin, insulin tolerance, and fasting plasma insulin. High fat diet eliminated the reduction in calorie intake observed after RYGB in ob/ob mice and promoted weight regain, although not to the same extent as in sham-operated mice. We conclude that leptin is required for the effects of RYGB on glucose homeostasis but not body weight or composition in mice. Our data also suggest that leptin may play a role in post-RYGB weight maintenance. Public Library of Science 2015-10-07 /pmc/articles/PMC4596552/ /pubmed/26445459 http://dx.doi.org/10.1371/journal.pone.0139960 Text en © 2015 Mokadem 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
Mokadem, Mohamad
Zechner, Juliet F.
Uchida, Aki
Aguirre, Vincent
Leptin Is Required for Glucose Homeostasis after Roux-en-Y Gastric Bypass in Mice
title Leptin Is Required for Glucose Homeostasis after Roux-en-Y Gastric Bypass in Mice
title_full Leptin Is Required for Glucose Homeostasis after Roux-en-Y Gastric Bypass in Mice
title_fullStr Leptin Is Required for Glucose Homeostasis after Roux-en-Y Gastric Bypass in Mice
title_full_unstemmed Leptin Is Required for Glucose Homeostasis after Roux-en-Y Gastric Bypass in Mice
title_short Leptin Is Required for Glucose Homeostasis after Roux-en-Y Gastric Bypass in Mice
title_sort leptin is required for glucose homeostasis after roux-en-y gastric bypass in mice
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4596552/
https://www.ncbi.nlm.nih.gov/pubmed/26445459
http://dx.doi.org/10.1371/journal.pone.0139960
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