Circadian Clocks Are Resounding in Peripheral Tissues

Ptitsyn, Andrey A.; Zvonic, Sanjin; Conrad, Steven A.; Scott, L. Keith; Mynatt, Randall L.; Gimble, Jeffrey M.

doi:10.1371/journal.pcbi.0020016

Cited by 118 publications

(134 citation statements)

References 23 publications

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“…Although these cells are known to express clock genes (Shimba et (Ando et al, 2005;Ptitsyn et al, 2006;Yang et al, 2006;Zvonic et al, 2006). Our data, therefore, suggest that some of the reported rhythmicity in murine WAT may derive from non-adipocyte cell types and/or rhythmical input signal(s).…”

Section: Discussionmentioning

confidence: 64%

Circadian Rhythmicity in Murine Pre-Adipocyte and Adipocyte Cells

Otway

Frost

Johnston

2009

Chronobiology International

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Adipose tissue is central to metabolic homeostasis, signalling in part through the secretion of molecules termed adipokines. Circadian rhythms play an important role in adipose physiology, with plasma adipokine concentration and ~20% of the murine adipose transcriptome undergoing24 h variation. However, due to the heterogeneity of adipose tissue and rhythmical input from both neuronal and humoral signals, the cellular basis of adipose rhythms is unclear. We tested the hypothesis that adipocyte cells contain a circadian clock that drives rhythmic mRNA expression and adipokine secretion. From the murine preadipocyte 3T3-L1 cell line, we generated populations of both pre-adipocytes and differentiated adipocytes. Cells were then treated with a 2 h serum pulse and sampled every 4 h over a 48 h period. Expression of clock gene, 'metabolic' gene (PPARα, PPARγ, SREBP1) and adipokine mRNA was analyzed by quantitative real-time PCR, and secretion of the adipokines leptin and adiponectin was measured in culture medium from differentiated adipocytes. In pre-adipocytes, we observed robust rhythms of clock genes Per2, Rev-erbα, and Dbp, but not of Per1, Cry1, Bmal1, or any of the 'metabolic' genes. Adipocytes produced similar temporal profiles of mRNA expression, albeit with a markedly reduced amplitude of Per2 and Dbp rhythms. Despite no circadian rhythm of adipokine mRNA expression, leptin accumulation in the culture medium suggested circadian control of leptin secretion from adipocytes. Adiponectin secretion showed temporal variation, but without any apparent circadian rhythmicity. Our data, therefore, suggest that an endogenous adipocyte clock controls the rhythmic expression of only a subset of genes that are reported to exhibit 24 h rhythmicity in murine adipose tissue. Moreover, secretion of leptin may also be regulated by the adipocyte clock.

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Section: Discussionmentioning

confidence: 64%

Circadian Rhythmicity in Murine Pre-Adipocyte and Adipocyte Cells

Otway

Frost

Johnston

2009

Chronobiology International

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“…RNA isolation and qRT-PCR Total RNA was isolated from the BAT, eWAT, iWAT, and liver tissues using TriReagent (MRC, Cincinnati, OH, USA) in accordance with the manufacturer's recommendations as previously published (Ptitysn et al 2006;. A Nanodrop ND-1000 Spectrophotometer (Wilmington, DE, USA) was used to determine total RNA concentrations, and 2 μg of total RNA was reverse-transcribed using Moloney Murine Leukemia Virus Reverse Transcriptase (MMLV-RT; Promega, Madison, WI, USA), with Oligo dT at 42°C…”

Section: Methodsmentioning

confidence: 99%

“…The problem can be mitigated by application of g test in phase continuum setting with digital filters ). We have also applied alternative tests for periodicity such as autocorrelation (as described in Zvonic et al 2006) and Pt test (Ptitsyn et al 2006a). …”

Section: Methodsmentioning

confidence: 99%

“…Global transcriptomic approaches by ourselves and others have demonstrated the diurnal/circadian oscillation of up to 20% of expressed genes in adipose tissue as well as the suprachiasmatic nuclei, liver, and heart (Akhtar et al 2002;Duffield et al 2002;Panda et al 2002a, b;Ueda et al 2002;Hogenesch et al 2003;Oishi et al 2003;Sato et al 2003Sato et al , 2004. Oscillating genes in adipose tissue included those encoding proteins related to glycolysis, lipolysis, steroidogenesis, redox potential, and iron/ heme metabolism (Ptitysn et al 2006;Zvonic et al 2006). While "conventional wisdom" (Monk 2005) assumes that biological age impacts circadian biology, this relationship in adipose tissue remains poorly defined.…”

Section: Introductionmentioning

confidence: 97%

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Biological aging alters circadian mechanisms in murine adipose tissue depots

Sutton

Ptitsyn

Floyd

et al. 2012

AGE

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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 AGE (2013) 35:533-547 DOI 10.1007 Electronic supplementary material The online version of this article (doi:10.1007/s11357-012-9389-7) contains supplementary material, which is available to authorized users. 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.

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“…Circadian rhythms of gene expression have been observed in adipose tissue [37,38], and the alteration of this gene expression rhythm has been associated with obesity [39,40]. Endocrine signals are also important for normal functions of adipose secretion.…”

Section: Discussionmentioning

confidence: 99%

Characterisation of insulin-resistant phenotype of cultured rat primary adipose cells

Xiang

et al. 2007

Diabetologia

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Aims/hypothesis We characterised insulin resistance, metabolic defects and endocrine dysfunction in cultured adipose cells and examined the autocrine or paracrine roles of cytokines/adipokines in the progression of insulin resistance. Materials and methods Rat primary adipose cells were prepared and cultured for 24 and 48 h. Insulin resistance and gene expression were examined by glucose uptake assay, cDNA microarray and real-time RT-PCR.Results After 24 h in culture, the fold increase of insulinstimulated glucose uptake in adipose cells was markedly reduced; after 48 h the response of the cells to insulin decreased. cDNA microarray analysis showed that the expression of 514 genes was altered in adipose cells after 24 h in culture. The dysregulated genes included those involved in the citric acid cycle and in fatty acid and pyruvate metabolism. Specifically, the following genes were all downregulated: genes encoding lipolytic and lipogenic enzymes; uncoupling protein 1 and 2 genes; peroxisome proliferator-activated receptor gamma, coactivator 1 alpha gene. This indicates that lipolytic and lipogenic activity, as well as mitochondria capacity decline in adipose cells cultured for 24 h. The mRNAs encoding 40 adipokines were also dysregulated in cultured cells. Strikingly, the dysregulated adipokines in cultured cells and in freshly isolated adipose cells from insulin-resistant Zucker fa/fa rats displayed a similar pattern with regard to protein functions. Also striking was the fact that progression of insulin resistance was promoted by the adipokines secreted from insulin-resistant adipose tissue or cells. Conclusions/interpretation Our data demonstrate that the impairment of metabolism and endocrine dysfunction in cultured adipose cells mimics the insulin resistance occurring in vivo. Cytokines and adipokines appear to play a critical role in the progression of insulin resistance in adipose cells.

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Circadian Clocks Are Resounding in Peripheral Tissues

Cited by 118 publications

References 23 publications

Circadian Rhythmicity in Murine Pre-Adipocyte and Adipocyte Cells

Circadian Rhythmicity in Murine Pre-Adipocyte and Adipocyte Cells

Biological aging alters circadian mechanisms in murine adipose tissue depots

Characterisation of insulin-resistant phenotype of cultured rat primary adipose cells

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