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Cited by 124Circadian rhythm and melatoninAdipose Tissue and MetabolismAdipokines, Inflammation, and Metabolic Diseases

Diurnal variation of the human adipose transcriptome and the link to metabolic disease

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Loboda, Andrey, Kraft, Walter K, Fine, Bernard, Joseph, Jeffrey, Nebozhyn, Michael, Zhang, Chunsheng, He, Yudong, Yang, Xia +11 more·2009·BMC Medical Genomics
DOI 10.1186/1755-8794-2-7PMC PMC2647943
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Abstract

Background: Circadian (diurnal) rhythm is an integral part of the physiology of the body; specifically, sleep, feeding behavior and metabolism are tightly linked to the light-dark cycle dictated by earth's rotation. Methods: The present study examines the effect of diurnal rhythm on gene expression in the subcutaneous adipose tissue of overweight to mildly obese, healthy individuals. In this well-controlled clinical study, adipose biopsies were taken in the morning, afternoon and evening from individuals in three study arms: treatment with the weight loss drug sibutramine/fasted, placebo/fed and placebo/fasted. Results: The results indicated that diurnal rhythm was the most significant driver of gene expression variation in the human adipose tissue, with at least 25% of the genes having had significant changes in their expression levels during the course of the day. The mRNA expression levels of core clock genes at a specific time of day were consistent across multiple subjects on different days in all three arms, indicating robust diurnal regulation irrespective of potential confounding factors. The genes essential for energy metabolism and tissue physiology were part of the diurnal signature. We hypothesize that the diurnal transition of the expression of energy metabolism genes reflects the shift in the adipose tissue from an energy-expending state in the morning to an energy-storing state in the evening. Consistent with this hypothesis, the diurnal transition was delayed by fasting and treatment with sibutramine. Finally, an in silico comparison of the diurnal signature with data from the publicly-available Connectivity Map demonstrated a significant association with transcripts that were repressed by mTOR inhibitors, suggesting a possible link between mTOR signaling, diurnal gene expression and metabolic regulation. Conclusion: Diurnal rhythm plays an important role in the physiology and regulation of energy metabolism in the adipose tissue and should be considered in the selection of novel targets for the treatment of obesity and other metabolic disorders.

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  • People who skip breakfast display a delayed activation of lipolysis along with an increase in adipose tissue production.

    “Previously it has been shown that people who skip breakfast display a delayed activation of lipolysis along with an increase in adipose tissue production [135, 136].”

    From International society of sports nutrition position stand: nutrient timing (2017) · cites this paper as [135]

    The Discussion (page unavailable) reports that fasting delayed the adipose tissue’s diurnal rhythm, extending its catabolic state into the afternoon. It does not report delayed activation of lipolysis or increased adipose tissue production in people who skip breakfast. (LLM, conf=0.85)

    Experimental — accuracy not yet measured

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Authors
Loboda, A., Kraft, W. K., Fine, B., Joseph, J., Nebozhyn, M., Zhang, C., He, Y., Yang, X., Wright, C., Morris, M., Chalikonda, I., Ferguson, M., Emilsson, V., Leonardson, A., Lamb, J., Dai, H., Schadt, E., Greenberg, H. E., & Lum, P. Y.
Affiliations
  • Merck & Co., Inc., Rahway, NJ, USA (United States) (US)
  • Thomas Jefferson University (US)
Corresponding author
Lum, Pek Yee
ORCID
Venue
BMC Medical Genomics
Publisher
Springer Science and Business Media LLC
Published
2009-02-09
Volume
2
Issue
1
Pages
7-7
ISSN
1755-8794 (ISSN-L)
DOI
10.1186/1755-8794-2-7
PMC
PMC2647943
OpenAlex
W2078965372
Cited by
124
References
53
Citations by year
2026: 2 · 2025: 1 · 2024: 6 · 2023: 5 · 2022: 3 · 2021: 9 · 2020: 21 · 2019: 3 · 2018: 6 · 2017: 9 · 2016: 7 · 2015: 7 · 2014: 3 · 2013: 7 · 2012: 8
FWCI
5.09
Type
journal article
Language
en
Open access
Licence
Locations
  • BMC Medical Genomics (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • The Medicine Forum (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • eScholarship (California Digital Library) (submittedVersion)
  • eScholarship (California Digital Library) (submittedVersion, cc-by)
Topics
  • Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
  • Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
  • Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
Keywords
circadian rhythm, diurnal gene expression, subcutaneous adipose tissue, transcriptome, core clock genes, energy metabolism, sibutramine, fasting, obesity, mTOR signaling, metabolic disorders

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