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Cited by 452Circadian rhythm and melatoninAdipokines, Inflammation, and Metabolic DiseasesDietary Effects on Health

Circadian Disruption Leads to Insulin Resistance and Obesity

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Shi, Shu-qun, Ansari, Tasneem S., McGuinness, Owen P., Wasserman, David H., Johnson, Carl Hirschie·2013·Current Biology
DOI 10.1016/j.cub.2013.01.048PMC PMC3595381
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Abstract

Background Disruption of circadian (daily) timekeeping enhances the risk of metabolic syndrome, obesity, and type 2 diabetes. While clinical observations have suggested that insulin action is not constant throughout the 24 hr cycle, its magnitude and periodicity have not been assessed. Moreover, when circadian rhythmicity is absent or severely disrupted, it is not known whether insulin action will lock to the peak, nadir, or mean of the normal periodicity of insulin action. Results We used hyperinsulinemic-euglycemic clamps to show a bona fide circadian rhythm of insulin action; mice are most resistant to insulin during their daily phase of relative inactivity. Moreover, clock-disrupted Bmal1-knockout mice are locked into the trough of insulin action and lack rhythmicity in insulin action and activity patterns. When rhythmicity is rescued in the Bmal1-knockout mice by expression of the paralogous gene Bmal2, insulin action and activity patterns are restored. When challenged with a high-fat diet, arhythmic mice (either Bmal1-knockout mice or wild-type mice made arhythmic by exposure to constant light) were obese prone. Adipose tissue explants obtained from high-fat-fed mice have their own periodicity that was longer than animals on a chow diet. Conclusions This study provides rigorous documentation for a circadian rhythm of insulin action and demonstrates that disturbing the natural rhythmicity of insulin action will disrupt the rhythmic internal environment of insulin sensitive tissue, thereby predisposing the animals to insulin resistance and obesity.

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  • Long-term desynchronization of circadian rhythms is associated with adverse metabolic health effects, including weight gain, increased body fat, obesity, impaired glucose tolerance, insulin resistance, higher blood pressure, elevated cholesterol levels, and elevated risk for cardiovascular diseases, diabetes, and metabolic syndrome.

    “Long-term desynchronization of circadian rhythms is associated with adverse metabolic health effects, including weight gain, increased body fat, obesity, impaired glucose tolerance, insulin resistance, higher blood pressure, and elevated cholesterol levels, as well as elevated risk for cardiovascular diseases, diabetes, and metabolic syndrome (18, 47–54).”

    From Meal timing and its role in obesity and associated diseases (2024) · cites this paper as [51]

    The Introduction links circadian desynchrony to disrupted body-weight and glucose/lipid regulation and to obesity, metabolic syndrome, and type 2 diabetes. The Discussion reports insulin resistance, elevated fasting glucose, and fat accumulation in clock-disrupted mice. The paper does not establish the full list: it does not report higher blood pressure, elevated cholesterol levels, or cardiovascular-disease risk as effects of long-term desynchronization, and it discusses glucose tolerance without reporting impaired tolerance as a result. (LLM, conf=0.85)

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Authors
Shi, S.-Q., Ansari, T. S., McGuinness, O. P., Wasserman, D. H., & Johnson, C. H.
Affiliations
Vanderbilt University (US)
Corresponding author
Johnson, Carl Hirschie
ORCID
Venue
Current Biology
Publisher
Elsevier BV
Published
2013-03
Volume
23
Issue
5
Pages
372-381
ISSN
0960-9822 (ISSN-L)
DOI
10.1016/j.cub.2013.01.048
PMC
PMC3595381
OpenAlex
W2007247773
Cited by
452
References
6
Citations by year
2026: 19 · 2025: 25 · 2024: 27 · 2023: 42 · 2022: 38 · 2021: 34 · 2020: 36 · 2019: 36 · 2018: 30 · 2017: 30 · 2016: 37 · 2015: 40 · 2014: 42 · 2013: 14 · 2012: 1
FWCI
23.94
Type
journal article
Language
en
Open access
Licence
Locations
  • Current Biology (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institutes of Health (5p60dk020593-31)
  • National Heart, Lung, and Blood Institute (R21HL102492)
  • National Institute of Mental Health (R21MH065910)
  • National Institute of Diabetes and Digestive and Kidney Diseases (P60-DK020593, U24DK059637, 2P60DK020593, DK 059637, U24DK076169)
Topics
  • Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
  • Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
  • Health Sciences › Medicine › Physiology › Dietary Effects on Health
Keywords
circadian rhythm, insulin action, insulin resistance, obesity, Bmal1, clock genes, metabolic syndrome, type 2 diabetes, high-fat diet, adipose tissue, constant light, activity patterns, hyperinsulinemic-euglycemic clamp
MeSH terms
Animals, Circadian Rhythm, Insulin, Insulin Resistance, Male, Obesity, Glucose Clamp Technique, Mice, Knockout, Mice, ARNTL Transcription Factors, Diet, High-Fat

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