The role of mPer2 clock gene in glucocorticoid and feeding rhythms

Yang, Shutong; Liu, Aiyi; Weidenhammer, Adam; Cooksey, Robert C.; McClain, Donald; Kim, Myung K.; Aguilera, Greti; Abel, E. Dale; Chung, Jay H.

doi:10.1210/en.2008-0705

Cited by 263Circadian rhythm and melatoninRegulation of Appetite and ObesityHypothalamic control of reproductive hormones

The role of mPer2 clock gene in glucocorticoid and feeding rhythms

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Yang, Shutong, Liu, Aiyi, Weidenhammer, Adam, Cooksey, Robert C., McClain, Donald, Kim, Myung K., Aguilera, Greti, Abel, E. Dale +1 more·2009·Endocrinology

DOI 10.1210/en.2008-0705PMC PMC2671901

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Abstract

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 impact glucocorticoid receptor-dependent glucose metabolism.
“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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(NEURO-) ENDOCRINE CIRCUITS OF CIRCADIAN APPETITE REGULATION
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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.
ORCID: Yang, Shutong
Liu, Aiyi
McClain, Donald
Kim, Myung K.
Abel, E. Dale
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
DOI: 10.1210/en.2008-0705
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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The role of mPer2 clock gene in glucocorticoid and feeding rhythms

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