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Assessment of the Metabolic Effects of Isocaloric 2:1 Intermittent Fasting in Mice
Published on: November 27, 2019
Hypothalamic Fkbp51 is induced by fasting, and elevated hypothalamic expression promotes obese phenotypes
Linda Yang1, Fumiko Isoda, Kelvin Yen
1Fishberg Dept. of Neuroscience, Mount Sinai School of Medicine, New York, NY 10029, USA.
American Journal of Physiology. Endocrinology and Metabolism
|February 10, 2012
Summary
Fasting increases FKBP51 gene expression in the hypothalamus, a brain region regulating energy balance. Overexpressing this gene promotes obesity, elevated corticosterone, and impaired glucose tolerance in mice.
Area of Science:
- Neuroscience
- Metabolic Research
- Molecular Biology
Background:
- The hypothalamus plays a critical role in regulating energy balance.
- Fasting can alter gene expression within the hypothalamus.
- FKBP51 (FK506 binding protein 5) is known to modulate glucocorticoid action.
Purpose of the Study:
- To identify hypothalamic genes induced by fasting.
- To investigate the role of Fkbp51 in energy balance and obesity.
- To determine if elevated hypothalamic Fkbp51 promotes obese phenotypes.
Main Methods:
- Microarray screening of hypothalamic genes in fasted mice.
- Quantitative analysis of Fkbp51 expression in mouse and rat hypothalamus.
- Adeno-associated virus-mediated gene transfer to overexpress Fkbp51 in the hypothalamus.
- Assessment of body weight, food intake, corticosterone levels, and glucose tolerance in mice on a high-fat diet.
Main Results:
- Fasting for 48 hours induced Fkbp51 expression in key hypothalamic nuclei (ventromedial, paraventricular, arcuate).
- Overexpression of hypothalamic Fkbp51 in mice led to elevated body weight within 2 weeks on a high-fat diet.
- Sustained weight gain, elevated corticosterone, and impaired glucose tolerance were observed in Fkbp51-overexpressing mice.
Conclusions:
- Hypothalamic Fkbp51 is induced by fasting.
- Elevated hypothalamic Fkbp51 promotes obesity and associated metabolic dysfunctions.
- Fkbp51 is a potential therapeutic target for obesity and metabolic disorders.
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