Circadian period of luciferase expression shortens with age in human mature adipocytes from obese patients

Isa Kolbe; María Paz Carrasco-Benso; Jesús López-Mínguez; Juan Lujan; Frank A.J.L. Scheer; Henrik Oster; Marta Garaulet

doi:10.1096/fj.201800441R

Circadian period of luciferase expression shortens with age in human mature adipocytes from obese patients

Isa Kolbe, María Paz Carrasco-Benso, Jesús López-Mínguez, Juan Lujan, Frank A.J.L. Scheer, Henrik Oster^*, Marta Garaulet

^*Corresponding author for this work

9 Citations (Scopus)

Abstract

Daily rhythms in physiology and behavior change with age. An unresolved question is to what extent such age-related alterations in circadian organization are driven by the central clock in the suprachiasmatic nucleus (SCN), modifying timing signals to contributing peripheral tissue oscillators, and are mediated by underlying changes in the local cellular oscillators themselves. Using a bioluminescence reporter approach, we sought to determine whether circadian clock function in human adipocytes from subcutaneous (SAT) and visceral (VAT) adipose tissues changeswith age. SAT andVAT biopsies were obtained from obese individuals during gastric bypass surgeries [n = 16; body mass index: 44.8 6 11.4 kg/m2; age: 44 6 9 yr (range: 30-58)]. Cells were isolated and transduced with a lentiviral circadian reporter construct [brain and muscle aryl hydrocarbon receptor nuclear translocator-like:luciferase (BMAL:LUC)], and bioluminescence was recorded over a period of 3 d. Human BMAL1:LUC adipocytes displayed a robust luminescence rhythm with comparable within-individual periods in mature and preadipocytes (P > 0.05).With increasing age, the circadian period decreased in mature adipocytes (P = 0.005) (b = 4 min/yr; P < 0.05). Our ex vivo approach indicated that ageing changes the organization of endogenous circadian oscillators in human adipocytes, independent of SCNsignaling.

Original language	English
Journal	FASEB Journal
Volume	33
Issue number	1
Pages (from-to)	175-180
Number of pages	6
ISSN	0892-6638
DOIs	https://doi.org/10.1096/fj.201800441R
Publication status	Published - 01.01.2019

Funding

This work as supported in part by The Spanish Department of Investigation, Development, and Innovation (SAF2017-84135-R) including cofunding from the Spanish Federation of Rare Diseases (FEDER), and U.S. National Institutes of Health (NIH), National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Grant R01DK105072 (to M.G.); German Research Foundation grants GRK-1957 and SFB-134 (to H.O.); and NIH NIDDK Grant R01 DK099512 and NIH National Heart, Lung and Blood Institute grants R01 HL118601 and R01 HL140574 (to F.A.J.L.S). H.O. is a Lichtenberg fellow of the Volkswagen Foundation. F.A.J.L.S. has received speaker fees from Bayer Healthcare (Montville, NJ, USA), Sentara Healthcare (Norfolk, VA, USA), Kellogg Company (Battle Creek, MI, USA), and Philips (Eindhoven, The Netherlands). The other authors declare no conflicts of interest.

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being
SDG 8 Decent Work and Economic Growth
SDG 10 Reduced Inequalities

Research Areas and Centers

Academic Focus: Center for Brain, Behavior and Metabolism (CBBM)

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Cite this

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abstract = "Daily rhythms in physiology and behavior change with age. An unresolved question is to what extent such age-related alterations in circadian organization are driven by the central clock in the suprachiasmatic nucleus (SCN), modifying timing signals to contributing peripheral tissue oscillators, and are mediated by underlying changes in the local cellular oscillators themselves. Using a bioluminescence reporter approach, we sought to determine whether circadian clock function in human adipocytes from subcutaneous (SAT) and visceral (VAT) adipose tissues changeswith age. SAT andVAT biopsies were obtained from obese individuals during gastric bypass surgeries [n = 16; body mass index: 44.8 6 11.4 kg/m2; age: 44 6 9 yr (range: 30-58)]. Cells were isolated and transduced with a lentiviral circadian reporter construct [brain and muscle aryl hydrocarbon receptor nuclear translocator-like:luciferase (BMAL:LUC)], and bioluminescence was recorded over a period of 3 d. Human BMAL1:LUC adipocytes displayed a robust luminescence rhythm with comparable within-individual periods in mature and preadipocytes (P > 0.05).With increasing age, the circadian period decreased in mature adipocytes (P = 0.005) (b = 4 min/yr; P < 0.05). Our ex vivo approach indicated that ageing changes the organization of endogenous circadian oscillators in human adipocytes, independent of SCNsignaling.",

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AU - Carrasco-Benso, María Paz

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AU - Lujan, Juan

AU - Scheer, Frank A.J.L.

AU - Oster, Henrik

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AB - Daily rhythms in physiology and behavior change with age. An unresolved question is to what extent such age-related alterations in circadian organization are driven by the central clock in the suprachiasmatic nucleus (SCN), modifying timing signals to contributing peripheral tissue oscillators, and are mediated by underlying changes in the local cellular oscillators themselves. Using a bioluminescence reporter approach, we sought to determine whether circadian clock function in human adipocytes from subcutaneous (SAT) and visceral (VAT) adipose tissues changeswith age. SAT andVAT biopsies were obtained from obese individuals during gastric bypass surgeries [n = 16; body mass index: 44.8 6 11.4 kg/m2; age: 44 6 9 yr (range: 30-58)]. Cells were isolated and transduced with a lentiviral circadian reporter construct [brain and muscle aryl hydrocarbon receptor nuclear translocator-like:luciferase (BMAL:LUC)], and bioluminescence was recorded over a period of 3 d. Human BMAL1:LUC adipocytes displayed a robust luminescence rhythm with comparable within-individual periods in mature and preadipocytes (P > 0.05).With increasing age, the circadian period decreased in mature adipocytes (P = 0.005) (b = 4 min/yr; P < 0.05). Our ex vivo approach indicated that ageing changes the organization of endogenous circadian oscillators in human adipocytes, independent of SCNsignaling.

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Circadian period of luciferase expression shortens with age in human mature adipocytes from obese patients

Abstract

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