Aryl hydrocarbon receptor nuclear translocator-like (BMAL1) is associated with susceptibility to hypertension and type 2 diabetes

Woon, Peng Yeong; Kaisaki, Pamela J.; Bragança, José; Bihoreau, Marie-Thérèse; Levy, Jonathan C.; Farrall, Martin; Guyader, Dominique

doi:10.1073/pnas.0703247104

Cited by 356 publications

(261 citation statements)

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“…That the mutation and genotypes of core clock genes are associated with metabolic diseases [15,[17][18][19] leads us to speculate that the circadian clock contributes to the development of diabetes. Oishi et al [29] demonstrated that clock function is preserved to a great extent in the livers, hearts and kidneys of mice with streptozotocininduced insulinopenic diabetes.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, we showed that the rhythmic expression of clock genes is blunted in the liver and visceral adipose tissues of KK-A y mice, a genetic model of type 2 diabetes [16]. In humans, genetic variations in the BMAL1 gene (also known as ARNTL) are reported to be associated with susceptibility to type 2 diabetes and hypertension [17]. Furthermore, CLOCK haplotypes are associated with metabolic syndrome [18] and non-alcoholic fatty liver disease [19].…”

Section: Introductionmentioning

confidence: 94%

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Clock gene expression in peripheral leucocytes of patients with type 2 diabetes

et al. 2008

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Aim/hypothesis Recent studies have demonstrated relationships between circadian clock function and the development of metabolic diseases such as type 2 diabetes. We investigated whether the peripheral circadian clock is impaired in patients with type 2 diabetes. Methods Peripheral leucocytes were obtained from eight patients with diabetes and six comparatively young nondiabetic volunteers at 09:00, 15:00, 21:00 and 03:00 hours (study 1) and from 12 male patients with diabetes and 14 agematched men at 09:00 hours (study 2). Transcript levels of clock genes (CLOCK, BMAL1 [also known as ARNTL], PER1, PER2, PER3 and CRY1) were determined by real-time quantitative PCR.Results In study 1, mRNA expression patterns of BMAL1, PER1, PER2 and PER3 exhibited 24 h rhythmicity in the leucocytes of all 14 individuals. The expression levels of these mRNAs were significantly (p<0.05) lower in patients with diabetes than in non-diabetic individuals at one or more time points. Moreover, the amplitudes of mRNA expression rhythms of PER1 and PER3 genes tended to diminish in patients with diabetes. In study 2, leucocytes obtained from patients with diabetes expressed significantly (p<0.05) lower transcript levels of BMAL1, PER1 and PER3 compared with leucocytes from control individuals, and transcript expression was inversely correlated with HbA 1c levels (ρ=−0.47 to −0.55, p<0.05). Conclusions/interpretation These results suggest that rhythmic mRNA expression of clock genes is dampened in peripheral leucocytes of patients with type 2 diabetes. The impairment of the circadian clock appears to be closely associated with the pathophysiology of type 2 diabetes in humans.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 94%

Clock gene expression in peripheral leucocytes of patients with type 2 diabetes

et al. 2008

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“…Genetic variations in human circadian clock genes have been associated with metabolic phenotypes. Haplotype analyses revealed that `il`h=gene polymorphisms are correlated with the development of metabolic syndrome, while certain _j^iN alleles are linked to type II diabetes and hypertension (Scott et al, 2007;Woon et al, 2007). These data propose that the transcription factors of the positive limb of the circadian clock may serve a protective role in the incidence of metabolic diseases.…”

Section: Circadian Control Of Metabolismmentioning

confidence: 93%

A Time to Fast, a Time to Feast: The Crosstalk between Metabolism and the Circadian Clock

Kovac

Husse

Oster

2009

Molecules and Cells

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The cyclic environmental conditions brought about by the 24 h rotation of the earth have allowed the evolution of endogenous circadian clocks that control the temporal alignment of behaviour and physiology, including the uptake and processing of nutrients. Both metabolic and circadian regulatory systems are built upon a complex feedback network connecting centres of the central nervous system and different peripheral tissues. Emerging evidence suggests that circadian clock function is closely linked to metabolic homeostasis and that rhythm disruption can contribute to the development of metabolic disease. At the same time, metabolic processes feed back into the circadian clock, affecting clock gene expression and timing of behaviour. In this review, we summarize the experimental evidence for this bimodal interaction, with a focus on the molecular mechanisms mediating this exchange, and outline the implications for clock-based and metabolic diseases.

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“…Rodents with clock gene mutations have dysfunctional glucose homeostasis, insulin secretion and sensitivity and fat and cholesterol metabolism (Rudic et al, 2004;Turek et al, 2005). Similarly, single nucleotide polymorphisms in Clock and Bmal1 genes in humans are associated with abnormal hepatic fat and glucose metabolism (Sookoian et al, 2007;Woon et al, 2007). …”

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confidence: 99%

Does the circadian system regulate lactation?

Plaut

Casey

2012

Animal

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Environmental variables such as photoperiod, heat, stress, nutrition and other external factors have profound effects on quality and quantity of a dairy cow's milk. The way in which the environment interacts with genotype to impact milk production is unknown; however, evidence from our laboratory suggests that circadian clocks play a role. Daily and seasonal endocrine rhythms are coordinated in mammals by the master circadian clock in the hypothalamus. Peripheral clocks are distributed in every organ and coordinated by signals from the master clock. We and others have shown that there is a circadian clock in the mammary gland. Approximately 7% of the genes expressed during lactation had circadian patterns including core clock and metabolic genes. Amplitude changes occurred in the core mammary clock genes during the transition from pregnancy to lactation and were coordinated with changes in molecular clocks among multiple tissues. In vitro studies using a bovine mammary cell line showed that external stimulation synchronized mammary clocks, and expression of the core clock gene, BMAL1, was induced by lactogens. Female clock/ clock mutant mice, which have disrupted circadian rhythms, have impaired mammary development and their offspring failed to thrive suggesting that the dam's milk production was not adequate enough to nourish their young. We envision that, in mammals, during the transition from pregnancy to lactation the master clock is modified by environmental and physiological cues that it receives, including photoperiod length. In turn, the master clock coordinates changes in endocrine milieu that signals peripheral tissues. In dairy cows, it is clear that changes in photoperiod during the dry period and/or during lactation influences milk production. We believe that the photoperiod effect on milk production is mediated, in part by the 'setting' of the master clock with light, which modifies peripheral circadian clocks including the mammary core clock and subsequently impacts milk yield and may impact milk composition.Keywords: mammary, lactation, circadian rhythm, photoperiod, metabolism ImplicationsThe circadian system coordinates internal physiological processes in mammals and synchronizes these processes to the animal's environment. We review the literature and discuss recent findings from our laboratory and others that suggest the circadian system regulates lactation, including coordinating changes in the dam's physiology needed to initiate and maintain lactation and mediating the photoperiod effect on milk production. Identification of environmental and physiological inputs that affect genes that control circadian rhythms will enable development of approaches to alter gene expression to maximize production efficiency in farm animals. IntroductionNearly all physiological and behavioral functions of animals are rhythmic including secretion patterns of hormones, sleep-wake cycle, metabolism and core body temperature.A circadian rhythm is a roughly 24-h cycle in the biochemical, physiological or behaviora...

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Aryl hydrocarbon receptor nuclear translocator-like (BMAL1) is associated with susceptibility to hypertension and type 2 diabetes

Cited by 356 publications

References 53 publications

Clock gene expression in peripheral leucocytes of patients with type 2 diabetes

Clock gene expression in peripheral leucocytes of patients with type 2 diabetes

A Time to Fast, a Time to Feast: The Crosstalk between Metabolism and the Circadian Clock

Does the circadian system regulate lactation?

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