Peripheral Circadian Clock Rhythmicity Is Retained in the Absence of Adrenergic Signaling

Reilly, Dermot F.; Curtis, Anne M.; Cheng, Yan; Westgate, Elizabeth J.; Rudic, R. Daniel; Paschos, Georgios K.; Morris, Jacqueline; Ouyang, Ming; Thomas, Steven; FitzGerald, Garret A.

doi:10.1161/atvbaha.107.152538

Cited by 57 publications

(49 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…33,34 However, this has not been reported in human AT until now. This persistence of in vitro gene expression oscillations strongly suggests its direct regulation by endogenous factors, which modulate the circadian expression of these genes in adipose explants in an autocrine manner.…”

mentioning

confidence: 89%

Expression of cortisol metabolism-related genes shows circadian rhythmic patterns in human adipose tissue

et al. 2009

View full text Add to dashboard Cite

Objective: To analyze, in morbid obese patients, the expression of several human genes regulating cortisol metabolism, such as glucocorticoid receptor (GR), 11b-hydroxysteroid dehydrogenase type 1 (11bHSD1), 11b-hydroxysteroid dehydrogenase type 2 (11bHSD2), stearoyl-acute regulatory protein (StAR), 5a-reductase type I (5a-R) and peroxisome proliferator-activated receptor-g (PPARg) in two different adipose depots. A second objective was to characterize the circadian rhythmicity of these genes in both adipose tissue (AT) regions. Design: Visceral and subcutaneous abdominal AT biopsies were obtained from obese patients (body mass index X40 kg m À2 ). To carry out rhythmic expression analysis, AT explants were cultured for 24 h and gene expression at times (T ) 0, 6, 12 and 18 h, was performed with quantitative real-time PCR. Result: GR, 11bHSD1 and PPARg genes were highly expressed in both subcutaneous and visceral depots. StAR and 5a-R genes were detected at lower levels. The expression of 11bHSD2 was quantified in both AT depots with a higher expression in the visceral depot (P ¼ 0.032). Both sexes had similar gene expression levels, except for 5a-R (P ¼ 0.002). The genes studied showed circadian rhythmicity being more robust in visceral than in subcutaneous AT. Genes ranged in anti-phase between both depots (P ¼ 0.002). This rhythmicity was maintained in an AT culture. Conclusion: We have shown for the first time circadian rhythmicity in glucocorticoid-related gene expression in human AT ex vivo. These results may have potential therapeutic implications with respect to the pathogenesis and treatment of diseases, such as obesity, type 2 diabetes and cardiovascular diseases.

show abstract

mentioning

confidence: 89%

Expression of cortisol metabolism-related genes shows circadian rhythmic patterns in human adipose tissue

et al. 2009

View full text Add to dashboard Cite

show abstract

“…Although these rhythms are mainly controlled by the suprachiasmatic nucleus of the hypothalamus, other peripheral tissues, such as muscle or liver, regulate their functions through the expression of their own clock genes (Cermakian and Boivin 2009). Indeed, the transcriptional program regulated by these genes appears to be highly tissue specific (Reilly et al 2008). In this respect, we have demonstrated that human adipose tissue (AT) expresses clock genes in both visceral (VAT) and subcutaneous (SAT) adipose tissues (Garaulet and Madrid 2009).…”

Section: Introductionmentioning

confidence: 92%

Influence of menopause on adipose tissue clock gene genotype and its relationship with metabolic syndrome in morbidly obese women

Morante

Gómez-Santos

Margareto³

et al. 2011

AGE

View full text Add to dashboard Cite

Menopausal women exhibit a loss of circadian coordination, a process that runs parallel with a redistribution of adipose tissue. However, the specific genetic mechanisms underlying these alterations have not been studied. Thus, the aim of the present study was to determine whether the development of menopause induces an alteration of the genes that control biological rhythms in human subcutaneous (SAT) and visceral AGE (2012) (VAT) adipose tissue, and whether changes in clock gene expression are involved in the increased risk of developing metabolic syndrome (MetS), which is frequently associated with menopause. To this end, VAT and SAT biopsies were taken in pre-(n=7) and postmenopausal (n=7) women at similar hours in the morning. RNA was extracted, and a microarray analysis was made. Data were confirmed by quantitative real-time polymerase chain reaction. Western blot and immunohistochemical analysis were also performed. When clock gene expression was compared between both groups of women, data in SAT showed that expression of the core clock gene period3 was significantly higher in postmenopausal women, while casein kinase-1δ, E1A-binding protein and cAMPresponsive element were preferentially expressed in the premenopausal group. In VAT, period2 (PER2) and v-myc myelocytomatosis viral oncogene expressions were significantly higher in the postmenopausal group. Western blot analysis indicated that PER2 and PER3 protein expression was also increased in postmenopausal women. In addition, several genes, including PER2, were differentially expressed depending on whether or not the patient met the MetS criteria. We conclude that menopause transition induces several changes in the genotype of the adipose tissue chronobiological machinery related to an increased risk of developing MetS.

show abstract

“…No direct evidence has been reported that catecholamine or nutrients (glucose or fatty acids) could affect the phase of circadian clock. 87 A recent report revealed that PPARg induces Bmal1 expression in cardiovascular organs, 43 suggesting that thiazolidinediones, an agonist of PPARg, may become a potential tool for manipulating the clock system.…”

Section: Roles Of the Peripheral Clock In Cardiovascular Diseasesmentioning

confidence: 99%

Circadian clock and vascular disease

Takeda

Maemura

2010

Hypertens Res

View full text Add to dashboard Cite

Cardiovascular functions, including blood pressure and vascular functions, show diurnal oscillation. Circadian variations have been clearly shown in the occurrence of cardiovascular events such as acute myocardial infarction. Circadian rhythm strongly influences human biology and pathology. The identification and characterization of mammalian clock genes revealed that they are expressed almost everywhere throughout the body in a circadian manner. In contrast to the central clock in the suprachiasmatic nucleus (SCN), the clock in each tissue or cell is designated as a peripheral clock. It is now accepted that peripheral clocks have their own roles specific to each peripheral organ by regulating the expression of clock-controlled genes (CCGs), although the oscillation mechanisms of the peripheral clock are similar to that of the SCN. However, little was known about how the peripheral clock in the vasculature contributes to the process of cardiovascular disorders. The biological clock allows each organ or cell to anticipate and prepare for changes in external stimuli. Recent evidence obtained using genetically engineered mice with disrupted circadian rhythm showed a novel function of the internal clock in the pathogenesis of endothelial dysfunction, hypertension and hemostasis. Loss of synchronization between the central and peripheral clock also contributes to the pathogenesis of cardiovascular diseases, as restoration of clock homeostasis could prevent disease progression. Identification of CCGs in each organ, as well as discovery of tools to manipulate the phase of each biological clock, will be of great help in establishing a novel chronotherapeutic approach to the prevention and treatment of cardiovascular disorders.

show abstract

Peripheral Circadian Clock Rhythmicity Is Retained in the Absence of Adrenergic Signaling

Cited by 57 publications

References 37 publications

Expression of cortisol metabolism-related genes shows circadian rhythmic patterns in human adipose tissue

Expression of cortisol metabolism-related genes shows circadian rhythmic patterns in human adipose tissue

Influence of menopause on adipose tissue clock gene genotype and its relationship with metabolic syndrome in morbidly obese women

Circadian clock and vascular disease

Contact Info

Product

Resources

About