Standards of evidence in chronobiology: critical review of a report that restoration of Bmal1 expression in the dorsomedial hypothalamus is sufficient to restore circadian food anticipatory rhythms in Bmal1-/- mice
Open accessAbstract
Daily feeding schedules generate food anticipatory rhythms of behavior and physiology that exhibit canonical properties of circadian clock control. The molecular mechanisms and location of food-entrainable circadian oscillators hypothesized to control food anticipatory rhythms are unknown. In 2008, Fuller et al reported that food-entrainable circadian rhythms are absent in mice bearing a null mutation of the circadian clock gene Bmal1 and that these rhythms can be rescued by virally-mediated restoration of Bmal1 expression in the dorsomedial nucleus of the hypothalamus (DMH) but not in the suprachiasmatic nucleus (site of the master light-entrainable circadian pacemaker). These results, taken together with controversial DMH lesion results published by the same laboratory, appear to establish the DMH as the site of a Bmal1-dependent circadian mechanism necessary and sufficient for food anticipatory rhythms. However, careful examination of the manuscript reveals numerous weaknesses in the evidence as presented. These problems are grouped as follows and elaborated in detail: 1. data management issues (apparent misalignments of plotted data), 2. failure of evidence to support the major conclusions, and 3. missing data and methodological details. The Fuller et al results are therefore considered inconclusive, and fail to clarify the role of either the DMH or Bmal1 in the expression of food-entrainable circadian rhythms in rodents.
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Many physiological systems that are regulated by circadian rhythms are also known to influence circadian function.
“In support of this theory, many physiological systems that are regulated by circadian rhythms are also known to influence circadian function.”
From The neuroendocrine control of the circadian system: Adolescent chronotype (2012) · cites this paper as [119]
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Physiological responses to food intake throughout the day
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- Authors
- Mistlberger, R. E., Buijs, R. M., Challet, E., Escobar, C., Landry, G. J., Kalsbeek, A., Pevet, P., & Shibata, S.
- Affiliations
- Simon Fraser University (CA)
- Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México (MX)
- Universidad Nacional Autónoma de México (MX)
- Netherlands Institute for Neuroscience (NL)
- Waseda University (JP)
- Corresponding author
- Mistlberger, Ralph E
- ORCID
- Venue
- Journal of Circadian Rhythms
- Publisher
- Ubiquity Press, Ltd.
- Published
- 2009-03-26
- Volume
- 7
- Issue
- 0
- Pages
- 3
- ISSN
- 1740-3391 (ISSN-L)
- PMC
- PMC2670815
- OpenAlex
- W2105240147
- Cited by
- 47
- References
- 40
- Citations by year
- 2026: 1 · 2023: 2 · 2021: 2 · 2020: 2 · 2019: 1 · 2018: 3 · 2017: 1 · 2016: 3 · 2014: 2 · 2013: 4 · 2012: 5
- FWCI
- 3.89
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Journal of Circadian Rhythms (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Pure Amsterdam UMC (publishedVersion)
- Summit (Simon Fraser University) (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Ubiquity Press Ltd - Journal of Circadian Rhythms (submittedVersion, cc-by)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Life Sciences › Neuroscience › Cognitive Neuroscience › Sleep and Wakefulness Research
- Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
- Keywords
- Bmal1, food anticipatory activity, dorsomedial hypothalamus, circadian clock, viral gene delivery, Bmal1 knockout mice, suprachiasmatic nucleus, circadian pacemaker, methodological errors
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