title: Biological aging alters circadian mechanisms in murine adipose tissue depots.
abstract: 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.
authors.affiliation: Protein Deficiency and Developmental Biology Laboratory, Pennington Biomedical Research Center, Louisiana State University System, 6400 Perkins Rd, Baton Rouge, LA 70808, USA. Gregory.Sutton@pbrc.edu
authors.forename: Gregory M
authors.initials: GM
authors.lastname: Sutton
authors.forename: Andrey A
authors.initials: AA
authors.lastname: Ptitsyn
authors.forename: Z Elizabeth
authors.initials: ZE
authors.lastname: Floyd
authors.forename: Gang
authors.initials: G
authors.lastname: Yu
authors.forename: Xiying
authors.initials: X
authors.lastname: Wu
authors.forename: Katie
authors.initials: K
authors.lastname: Hamel
authors.forename: Forum S
authors.initials: FS
authors.lastname: Shah
authors.forename: Armand
authors.initials: A
authors.lastname: Centanni
authors.forename: Kenneth
authors.initials: K
authors.lastname: Eilertsen
authors.forename: Indu
authors.initials: I
authors.lastname: Kheterpal
authors.forename: Susan
authors.initials: S
authors.lastname: Newman
authors.forename: Claudia
authors.initials: C
authors.lastname: Leonardi
authors.forename: Michael A
authors.initials: MA
authors.lastname: Freitas
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Bunnell
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Gimble
mesh_terms: D050156:Adipogenesis / Q000502:physiology*; D000273:Adipose Tissue / Q000502:physiology*; D000375:Aging / Q000502:physiology*; D000818:Animals; D002454:Cell Differentiation; D002940:Circadian Rhythm / Q000502:physiology*; D004195:Disease Models, Animal; D005500:Follow-Up Studies; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL