ABSTRACT
The hypothalamus controls food intake by integrating nutrient signals, of which one of the most important is glucose. Consequently, impairments in hypothalamic glucose-sensing mechanisms are associated with hyperphagia and obesity. Environmental enrichment (EE) is an animal housing protocol that provides complex sensory, motor, and social stimulations and has been proven to reduce adiposity in laboratory mice. However, the mechanism by which EE promotes adiposity-suppressing effect remains incompletely understood. Neurotrophic factors play an important role in the development and maintenance of the nervous system, but they are also involved in the hypothalamic regulation of feeding. Brain-derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF) are expressed in the hypothalamus and their expression is stimulated by glucose. EE is associated with increased expression of Bdnf mRNA in the hypothalamus. Therefore, we hypothesized that EE potentiates the anorectic action of glucose by altering the expression of neurotrophic factor genes in the hypothalamus. Male C57BL/6 mice were maintained under standard or EE conditions to investigate the feeding response to glucose and the associated expression of feeding-related neurotrophic factor genes in the hypothalamus. Intraperitoneal glucose injection reduced food intake in both control and EE mice with a significantly greater reduction in the EE group compared to the control group. EE caused a significantly enhanced response of Gdnf mRNA expression to glucose without altering basal Gdnf mRNA expression and Bdnf mRNA response to glucose. These findings suggest that EE enhances glucose-induced feeding suppression, at least partly, by enhancing hypothalamic glucose-sensing ability that involves GDNF.
Acknowledgments
We thank Ms. Pei San Lew for her assistance.
Disclosure statement
No potential conflict of interest was reported by the author(s).
Data availability statement
All data will be made available from the corresponding author upon request.
Authors’ contributions
T.M. Mizuno and M.S. Aldhshan conceived and designed the study and performed data analyses. T.M. Mizuno wrote the manuscript. M.S. Aldhshan collected data, performed statistical analyses, and wrote the first draft of the manuscript. All authors contributed to the final editing of the manuscript.
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Funding
Notes on contributors
Muhammad S. Aldhshan
Muhammad S. Aldhshan is a previous graduate student who contributed to the project. He obtained his Bachelor of Dental Surgery and Master’s degree in Physiology from Sinai University and the University of Manitoba, respectively.
Tooru M. Mizuno
Tooru M. Mizuno is a professor in the Department of Physiology & Pathophysiology at the University of Manitoba. He obtained his Master’s degree in Animal Husbandry and PhD in Physiology from the University of Miyazaki and Yokohama City University, respectively.