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The Role of mPer2 Clock Gene in Glucocorticoid and Feeding Rhythms
Open accessAbstract
The circadian clock synchronizes the activity level of an organism to the light-dark cycle of the environment. Energy intake, as well as energy metabolism, also has a diurnal rhythm. Although the role of the clock genes in the sleep-wake cycle is well characterized, their role in the generation of the metabolic rhythms is poorly understood. Here, we use mice deficient in the clock protein mPer2 to study how the circadian clock regulates two critical metabolic rhythms: glucocorticoid and food intake rhythms. Our findings indicate that mPer2-/- mice do not have a glucocorticoid rhythm even though the corticosterone response to hypoglycemia, ACTH, and restraint stress is intact. In addition, the diurnal feeding rhythm is absent in mPer2-/- mice. On high-fat diet, they eat as much during the light period as they do during the dark period and develop significant obesity. The diurnal rhythm of neuroendocrine peptide alphaMSH, a major effector of appetite control, is disrupted in the hypothalamus of mPer2-/- mice even though the diurnal rhythm of ACTH, the alphaMSH precursor, is intact. Peripheral injection of alphaMSH, which has been shown to enter the brain, restored the feeding rhythm and induced weight loss in mPer2-/- mice. These findings emphasize the requirement of mPer2 in appetite control during the inactive period and the potential role of peripherally administered alphaMSH in restoring night-day eating pattern in individuals with circadian eating disorders such as night-eating syndrome, which is also associated with obesity.
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“Per2 null mice exhibit no glucocorticoid oscillations, indicating that PER2 may also impact glucocorticoid receptor (GR)-dependent glucose metabolism [24,25].”
From Circadian control of glucose metabolism (2014) · cites this paper as [25]
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Metadata
- Authors
- Yang, S., Liu, A., Weidenhammer, A., Cooksey, R. C., McClain, D., Kim, M. K., Aguilera, G., Abel, E. D., & Chung, J. H.
- Affiliations
- National Institutes of Health (US)
- University of Utah (US)
- Corresponding author
- Chung, Jay H.
- Venue
- Endocrinology
- Publisher
- The Endocrine Society
- Published
- 2009-01-29
- Volume
- 150
- Issue
- 5
- Pages
- 2153-2160
- ISSN
- 0013-7227 (ISSN-L)
- 1945-7170
- PMC
- PMC2671901
- OpenAlex
- W2163695413
- Cited by
- 263
- References
- 47
- Citations by year
- 2026: 3 · 2025: 10 · 2024: 11 · 2023: 23 · 2022: 13 · 2021: 14 · 2020: 14 · 2019: 11 · 2018: 17 · 2017: 12 · 2016: 12 · 2015: 13 · 2014: 20 · 2013: 18 · 2012: 17
- FWCI
- 10.47
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Endocrinology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute of Diabetes and Digestive and Kidney Diseases
- National Institute of Child Health and Human Development
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
- Keywords
- mPer2, circadian clock, feeding rhythm, diurnal cycle, appetite regulation, hypothalamus, high-fat diet, obesity, corticosterone, ACTH, restraint stress, night eating syndrome, weight loss
- MeSH terms
- alpha-MSH, Animals, Circadian Rhythm, Corticosterone, Feeding Behavior, Glucocorticoids, Hyperphagia, Hypothalamus, Mice, Inbred C57BL, Nuclear Proteins, Stress, Physiological, Transcription Factors, Photoperiod, Mice, Knockout, Cell Cycle Proteins, Leptin, Mice, Period Circadian Proteins
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