The Circadian Clock in White and Brown Adipose Tissue: Mechanistic, Endocrine, and Clinical Aspects
. Endocrine reviews 2018
, 261 - 273. Publisher's VersionAbstract
Obesity is a major risk factor for the development of illnesses, such as insulin resistance and hypertension, and has become a serious public health problem. Mammals have developed a circadian clock located in the hypothalamic suprachiasmatic nuclei (SCN) that responds to the environmental light-dark cycle. Clocks similar to the one located in the SCN are found in peripheral tissues, such as the kidney, liver, and adipose tissue. The circadian clock regulates metabolism and energy homeostasis in peripheral tissues by mediating activity and/or expression of key metabolic enzymes and transport systems. Knockouts or mutations in clock genes that lead to disruption of cellular rhythmicity have provided evidence to the tight link between the circadian clock and metabolism. In addition, key proteins play a dual role in regulating the core clock mechanism, as well as adipose tissue metabolism, and link circadian rhythms with lipogenesis and lipolysis. Adipose tissues are distinguished as white, brown, and beige (or brite), each with unique metabolic characteristics. Recently, the role of the circadian clock in regulating the differentiation into the different adipose tissues has been investigated. In this review, the role of clock proteins and the downstream signaling pathways in white, brown, and brite adipose tissue function and differentiation will be reviewed. In addition, chronodisruption and metabolic disorders and clinical aspects of circadian adiposity will be addressed.
The Circadian Clock Drives Mast Cell Functions in Allergic Reactions
. Frontiers in immunology 2018
1526 - 1526. Publisher's VersionAbstract
Allergic diseases are known to vary in the severity of their symptoms throughout the day/night cycle. This rhythmicity is also observed in mast cell function and responsiveness. Mast cells are key effector cells of allergic reactions and release cytokines, chemokines, and important inflammatory mediators such as histamine, which have been shown to display diurnal variation. Recent research clarified that mast cells are controlled by their internal clock-which is regulated by a specific set of clock genes-as well as external factors such as light sensed by the suprachiasmatic nuclei, hormonal status, or diet. Here, we give an overview of the connections between circadian clock, mast cells, and allergic disease. Further work aimed at studying the role of chronotherapy/chronomedicine should take into account this rhythmic nature of not only mast cells but also the immune responses generated by mast cell signaling.
P334 Does the circadian clock have a role in the pathogenesis of inflammatory bowel disease (IBD)?
. Journal of Crohn's and Colitisecco-jcc 2018
, S270 - S271. Publisher's VersionAbstract
Sleep dysfunction modifies the immune system and has been implicated as a potential trigger of IBD flares. Sleep dysfunction also alters the synchrony among clock genes leading to disruption of overall circadian regulation. Specifically, in the intestine, it is manifested by increased gut cellular permeability. We hypothesised that changes in mucosal immune balance may be reflected by alterations in the circadian clock and constitute an unattended pathogenic mechanism of IBD. Our aim was to investigate intestinal and systemic clock gene expression (in patients with newly diagnosed IBD and in healthy controls).Patients and controls were recruited upon diagnostic endoscopic evaluation. Demographics, familial medical history, sleep questionnaires, disease activity indices, and endoscopic scores were recorded. Anthropometric parameters, C-reactive protein (CRP), albumin, haemoglobin (Hb), and fecal calprotectin (Fcal) were measured as well. Peripheral blood and tissue samples were analysed for clock gene (Clock, Bmal1, Cry1, Cry2, Per1, and Per2) expression.Of the 32 participants recruited (age 8–25 years, median: 16.1), 14 had newly diagnosed IBD and 18 were healthy controls. Age, gender, sleep questionnaire scores, and time of endoscopy were not statistically different between the groups. Hb, CRP, and Fcal levels were significantly higher in the IBD compared with the healthy controls group (p < 0.05), while albumin was significantly lower (p < 0.05). Clock gene expression (Clock, Cry1, Cry2, Per1, and Per2) in WBC was decreased in newly diagnosed IBD patients compared with health controls (p < 0.05). Similarly, the expression level of the aforementioned genes was lower in inflamed intestinal tissues (p < 0.05). Interestingly, similar reduction in clock gene expression was seen even in healthy (non-inflamed) intestinal tissue from IBD patients (p < 0.05).Clock gene expression is reduced in both inflamed and non-inflamed intestinal tissue in patients with newly diagnosed IBD. Moreover, IBD patients show a systemic reduction in clock gene expression. Our findings may lead to new therapeutic approaches and strategies as well as serve as diagnostic tools in IBD.
Circadian rhythms, nutrition and implications for longevity in urban environments
. Proceedings of the Nutrition Society 2018
, 216-222. Publisher's VersionAbstract
Presently, about 12% of the population is 65 years or older and by the year 2030 that figure is expected to reach 21%. In order to promote the well-being of the elderly and to reduce the costs associated with health care demands, increased longevity should be accompanied by ageing attenuation. Energy restriction, which limits the amount of energy consumed to 60–70% of the daily intake, and intermittent fasting, which allows the food to be available ad libitum every other day, extend the life span of mammals and prevent or delay the onset of major age-related diseases, such as cancer, diabetes and cataracts. Recently, we have shown that well-being can be achieved by resetting of the circadian clock and induction of robust catabolic circadian rhythms via timed feeding. In addition, the clock mechanism regulates metabolism and major metabolic proteins are key factors in the core clock mechanism. Therefore, it is necessary to increase our understanding of circadian regulation over metabolism and longevity and to design new therapies based on this regulation. This review will explore the present data in the field of circadian rhythms, ageing and metabolism.