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  Insulin directly regulates the circadian clock in adipose tissue

Tuvia, N., Pivovarova-Ramich, O., Murahovschi, V., Lück, S., Grudziecki, A., Ost, A.-C., et al. (2021). Insulin directly regulates the circadian clock in adipose tissue. Diabetes, 70(6), 1985-1999. doi:10.2337/db20-0910.

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Tuvia, Neta1, Author
Pivovarova-Ramich, Olga1, Author
Murahovschi, Veronica1, Author
Lück, Sarah1, Author
Grudziecki, Astrid1, Author
Ost, Anne-Catrin1, Author
Kruse, Michael1, Author
Nikiforova, V.2, Author              
Osterhoff, Martin1, Author
Gottmann, Pascal1, Author
GÖgebakan, {Ö}zlem1, Author
Sticht, Carsten1, Author
Gretz, Norbert1, Author
Schupp, Michael1, Author
Schürmann, Annette1, Author
Rudovich, Natalia1, Author
Pfeiffer, Andreas F.H.1, Author
Kramer, Achim1, Author
Affiliations:
1External Organizations, ou_persistent22              
2System Integration, Department Willmitzer, Max Planck Institute of Molecular Plant Physiology, Max Planck Society, ou_1753349              

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 Abstract: Adipose tissue (AT) is a key metabolic organ which functions are rhythmically regulated by an endogenous circadian clock. Feeding is a zeitgeber aligning the clock in AT with the external time but mechanisms of this regulation remain largely unclear. We tested the hypothesis that postprandial changes of the hormone insulin directly entrain circadian clocks in AT and investigated transcriptional-dependent mechanism of this regulation. We analysed gene expression in subcutaneous AT (SAT) of obese subjects collected before and after the hyperinsulinemic-euglycemic clamp (EC) or control saline infusion (SC). The expression of core clock gene PER2, PER3 and NR1D1 in SAT were differentially changed upon insulin and saline infusion suggesting insulin-dependent clock regulation. In human stem cell-derived adipocytes, mouse 3T3-L1 cells and AT explants from mPer2Luc knockin mice, insulin induced a transient increase of the Per2 mRNA and protein expression leading to the phase shift of circadian oscillations and showing similar effects for Per1. Insulin effects were dependent on the region between the -64 and -43 in the Per2 promoter, but not on CRE and E-box elements. Our results demonstrate that insulin directly regulates circadian clocks in AT and isolated adipocytes and thus represent a primary mechanism of feeding-induced AT clock entrainment.

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Language(s): eng - English
 Dates: 2021-09-10
 Publication Status: Published in print
 Pages: -
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 Table of Contents: -
 Rev. Type: -
 Identifiers: DOI: 10.2337/db20-0910
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Title: Diabetes
Source Genre: Journal
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Publ. Info: New York : American Diabetes Association
Pages: - Volume / Issue: 70 (6) Sequence Number: - Start / End Page: 1985 - 1999 Identifier: ISSN: 0012-1797
CoNE: https://pure.mpg.de/cone/journals/resource/110978977971732