, Volume 35, Issue 3, pp 533–547 | Cite as

Biological aging alters circadian mechanisms in murine adipose tissue depots

  • Gregory M. Sutton
  • Andrey A. Ptitsyn
  • Z. Elizabeth Floyd
  • Gang Yu
  • Xiying Wu
  • Katie Hamel
  • Forum S. Shah
  • Armand Centanni
  • Kenneth Eilertsen
  • Indu Kheterpal
  • Susan Newman
  • Claudia Leonardi
  • Michael A. Freitas
  • Bruce A. Bunnell
  • Jeffrey M. Gimble


Biological aging alters the metabolism and volume of adipose tissue depots. Recent evidence suggests that circadian mechanisms play a role in promoting adipogenesis, obesity, and lipodystrophy. The current study compared cohorts of younger (5–9 months) and older (24–28 months) C57BL/6 mice as a function of biological age and circadian time. Advanced age significantly reduced the weight of the brown, epididymal, inguinal, and retroperitoneal adipose depots but not total body weight. The older mice reduced their physical activity by >50% and delayed their activity initiation after light offset. The expressed transcriptome in brown and white adipose depots and liver of both cohorts displayed evidence of circadian rhythmicity; however, the oscillating mRNAs differed significantly between age groups and across tissues. The amplitude of Cry1, a component of the negative arm of the circadian apparatus, and downstream regulators such as Rev-erbα were elevated in the older relative to the younger cohorts as a function of circadian time. Overall, transcript levels differed significantly for 557 (inguinal adipose), 1,016 (liver), and 1,021 (brown adipose) expressed sequences between the cohorts as a function of age. These included transcripts encoding proteins within the canonical and non-canonical Wnt pathways. Since the Wnt pathway regulates adipose stem cell differentiation and shares a critical enzyme, glycogen synthase kinase 3β, with the circadian mechanism, the intersection between these two fundamental regulatory mechanisms merits further investigation with respect to biological aging of adipose tissues.


Brown adipose Circadian Liver Oscillation Transcriptomics White adipose 

Supplementary material

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Supplement Figure 1a

Analysis of Circadian Gene Oscillation by qRT-PCR. Total RNA isolated from brown adipose tissue (Fig. 1), epididymal WAT (Fig. 2), inguinal WAT (Fig. 3), and liver (Fig. 4) of younger and older mice was harvested at serial 4-h time points beginning at 0700 hours and continuing until 0300 hours during a single 24-h period. The level of expression of the following mRNAs representative of the circadian apparatus and adipogenesis was determined and normalized relative to cyclophilin B: Bmal1, Cry1, Cry2, DBP, E4BP4, Leptin, LPL, Npas2, Per1, PGC-1, PPARγ, Rev-Erbα, and Rev-Erbβ. Values presented are the mean ± SD, and these have been double-plotted. (JPEG 94 kb)

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Supplemental Table 1The forward and reverse primers as well as the PubMed accession numbers used for qRT-PCR are listed in Table 8. (DOC 34 kb)
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Supplemental Table 2The transcripts that were expressed differentially between the young and old cohorts as a function of biological age in two or more tissues are summarized in Table 7. Shared transcripts in BAT/iWAT, BAT/Liver, and iWAT/Liver as well as all three tissues are displayed. (DOC 113 kb)


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Copyright information

© American Aging Association 2012

Authors and Affiliations

  • Gregory M. Sutton
    • 1
  • Andrey A. Ptitsyn
    • 2
  • Z. Elizabeth Floyd
    • 3
  • Gang Yu
    • 4
  • Xiying Wu
    • 4
  • Katie Hamel
    • 4
  • Forum S. Shah
    • 4
  • Armand Centanni
    • 1
  • Kenneth Eilertsen
    • 5
  • Indu Kheterpal
    • 6
  • Susan Newman
    • 7
  • Claudia Leonardi
    • 8
    • 11
  • Michael A. Freitas
    • 9
  • Bruce A. Bunnell
    • 10
  • Jeffrey M. Gimble
    • 4
  1. 1.Protein Deficiency and Developmental Biology Laboratory, Pennington Biomedical Research CenterLouisiana State University SystemBaton RougeUSA
  2. 2.Whitney Laboratory for Marine BioscienceUniversity of FloridaSt. AugustineUSA
  3. 3.Ubiquitin Biology, Pennington Biomedical Research CenterLouisiana State University SystemBaton RougeUSA
  4. 4.Stem Cell Biology, Pennington Biomedical Research CenterLouisiana State University SystemBaton RougeUSA
  5. 5.Epigenetics and Nuclear Reprogramming, Pennington Biomedical Research CenterLouisiana State University SystemBaton RougeUSA
  6. 6.Protein Structural Biology Laboratories, Pennington Biomedical Research CenterLouisiana State University SystemBaton RougeUSA
  7. 7.Genomics, Pennington Biomedical Research CenterLouisiana State University SystemBaton RougeUSA
  8. 8.Biostatistics Core Facilities, Pennington Biomedical Research CenterLouisiana State University SystemBaton RougeUSA
  9. 9.The Ohio State University Medical CenterColumbusUSA
  10. 10.Center for Stem Cell Research and Regenerative Medicine and Department of PharmacologyTulane University Health Sciences CenterNew OrleansUSA
  11. 11.Louisiana State University Health Science CenterSchool of Public HealthNew OrleansUSA

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