Abstract
Circadian rhythms make a critical contribution to endocrine functions that involve adipose tissue. These contributions are made at the systemic, organ and stem cell levels. The transcription factors and enzymes responsible for the maintenance of circadian rhythms in adipose depots and other peripheral tissues that are metabolically active have now been identified. Furthermore, the circadian regulation of glucose and lipid metabolism is well-established. Animal and human models provide strong evidence that disturbances in circadian pathways are associated with an increased risk of type 2 diabetes mellitus, obesity and their comorbidities. Thus, circadian mechanisms represent a novel putative target for therapy in patients with metabolic diseases.
Key Points
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Circadian mechanisms oscillate because of the continuous operation of a transcriptional regulatory feedback loop
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Although circadian mechanisms were first associated with the body's central clock in the brain, they also operate in adipose tissue and other metabolically active peripheral tissues
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Adipose tissue function exhibits circadian oscillations in adipokine secretion, glucose and lipid metabolism and stem cell differentiation pathways
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Heme is an agonist for a specific nuclear hormone receptor protein in the circadian feedback loop, and studies are underway to uncover related molecules
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Oncologists have successfully exploited chronotherapy and the timing of drug delivery to maximize the benefits and minimize the adverse effects of chemotherapy
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Circadian-selective drugs and knowledge of adipose chronobiology could improve the prevention and treatment of endocrine disorders related to adipose tissue, including diabetes mellitus, the metabolic syndrome and obesity
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Acknowledgements
The authors wish to thank their colleagues in the Stem Cell Laboratory, Pennington Biomedical Research Center, Baton Rouge, LA, USA, and the Center for Stem Cell Research and Regenerative Medicine, Tulane University, New Orleans, LA, USA, for their comments and input; Ms. Laura Dallam for editorial and administrative assistance; Dr. Xiying Wu for assistance in the preparation of figures; and the Pennington Biomedical Research Foundation for funding.
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J. M. Gimble and A. A. Ptitsyn researched data for the article. J. M. Gimble, G. M. Sutton, B. A. Bunnell and Z. E. Floyd provided substantial contributions to the discussion of the content. J. M. Gimble and B. A. Bunnell wrote the article. All authors reviewed and edited the manuscript before submission.
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Gimble, J., Sutton, G., Bunnell, B. et al. Prospective influences of circadian clocks in adipose tissue and metabolism. Nat Rev Endocrinol 7, 98–107 (2011). https://doi.org/10.1038/nrendo.2010.214
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DOI: https://doi.org/10.1038/nrendo.2010.214
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