Journal article
Leptin Is Required for Glucose Homeostasis after Roux-en-Y Gastric Bypass in Mice
PloS one, Vol.10(10), pp.e0139960-e0139960
2015
DOI: 10.1371/journal.pone.0139960
PMCID: PMC4596552
PMID: 26445459
Abstract
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.
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.
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.
Details
- Title: Subtitle
- Leptin Is Required for Glucose Homeostasis after Roux-en-Y Gastric Bypass in Mice
- Creators
- Mohamad Mokadem - Fraternal Order of Eagles Diabetes Research Center, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa, 52242, United States of America; Division of Gastroenterology and Hepatology, Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa, 52242, United States of AmericaJuliet F Zechner - Division of Hypothalamic Research, Department of Internal Medicine, UT Southwestern Medical Center, Dallas, Texas, 75390, United States of America; Division of Digestive and Liver Diseases, Department of Internal Medicine, UT Southwestern Medical Center, Dallas, Texas, 75390, United States of AmericaAki Uchida - Division of Hypothalamic Research, Department of Internal Medicine, UT Southwestern Medical Center, Dallas, Texas, 75390, United States of AmericaVincent Aguirre - Division of Hypothalamic Research, Department of Internal Medicine, UT Southwestern Medical Center, Dallas, Texas, 75390, United States of America; Division of Digestive and Liver Diseases, Department of Internal Medicine, UT Southwestern Medical Center, Dallas, Texas, 75390, United States of America
- Resource Type
- Journal article
- Publication Details
- PloS one, Vol.10(10), pp.e0139960-e0139960
- DOI
- 10.1371/journal.pone.0139960
- PMID
- 26445459
- PMCID
- PMC4596552
- NLM abbreviation
- PLoS One
- ISSN
- 1932-6203
- eISSN
- 1932-6203
- Publisher
- Public Library of Science
- Grant note
- DK091511 / NIDDK NIH HHS DK100085 / NIDDK NIH HHS DK0073077 / NIDDK NIH HHS DK007745 / NIDDK NIH HHS F32 DK100085 / NIDDK NIH HHS K08 DK091511 / NIDDK NIH HHS T32 DK007745 / NIDDK NIH HHS
- Language
- English
- Date published
- 2015
- Academic Unit
- Gastroenterology and Hepatology; Internal Medicine
- Record Identifier
- 9984094585302771
Metrics
31 Record Views