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Updated: May 22, 2026
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Assessment of the Metabolic Effects of Isocaloric 2:1 Intermittent Fasting in Mice
Published on: November 27, 2019
Melanocortin-3 receptor regulates the normal fasting response
Benjamin J Renquist1, Jonathan G Murphy, Emily A Larson
1Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
Summary
Melanocortin-3 receptor deficiency impairs the body's ability to communicate nutritional status, leading to metabolic dysfunction. This defect affects fat breakdown, liver fat storage, and hormonal responses to fasting.
Area of Science:
- Endocrinology
- Metabolic research
- Physiology
Background:
- Melanocortin-3 receptor-deficient (MC3-R(-/-)) mice display mild obesity without changes in eating or metabolism.
- MC3-R deletion is linked to increased adiposity, reduced lean mass, and altered adipose tissue inflammation.
Purpose of the Study:
- To investigate the role of MC3-R in regulating metabolic responses to fasting.
- To elucidate the impact of MC3-R deficiency on the hypothalamic-pituitary-adrenal (HPA) axis and nutrient partitioning.
Main Methods:
- Phenotypic analysis of MC3-R(-/-) mice under fasting and refeeding conditions.
- Assessment of white adipose tissue lipolysis and liver triglyceride accumulation.
- Evaluation of HPA axis activity, including corticosterone levels and activation patterns.
Main Results:
- MC3-R(-/-) mice show defective fasting-induced white adipose tissue lipolysis and increased liver triglyceride accumulation.
- Fasting-induced refeeding responses and HPA axis regulation are impaired in MC3-R(-/-) mice.
- Elevated nadir corticosterone and blunted fasting-induced HPA axis activation were observed.
Conclusions:
- MC3-R is essential for signaling nutritional status to central and peripheral tissues involved in nutrient partitioning.
- MC3-R deficiency contributes significantly to the observed metabolic phenotype, including features resembling Cushing syndrome.
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