https://genie.weizmann.ac.il/pubs/2014_Zeevi.pdf

Transkingdom Control of Microbiota Diurnal Oscillations Promotes Metabolic Homeostasis

The Meter of Metabolism

Shift work and cancer risk: potential mechanistic roles of circadian disruption, light at night, and sleep deprivation.

The Per-Arnt-Sim (PAS) domain is conserved across the kingdoms of life and found in an ever-growing list of proteins. This domain can bind to and sense endogenous or xenobiotic small molecules such as molecular oxygen, cellular metabolites, or polyaromatic hydrocarbons. Members of this family are often found in pathways that regulate responses to environmental change; in mammals these include the hypoxia, circadian, and dioxin response pathways. These pathways function in development and throughout life to regulate cellular, organ, and whole-organism adaptive responses. Remarkably, in the case of the clock, this adaptation includes anticipation of environmental change. In this review, we summarize the roles of PAS domain–containing proteins in mammals. We provide structural evidence that functionally classifies both known and unknown biological roles. Finally, we discuss the role of PAS proteins in anticipation of and adaptation to environmental change.

Mammalian Per-Arnt-Sim Proteins in Environmental Adaptation

Adrenal glucocorticoids are major modulators of multiple functions, including energy metabolism, stress responses, immunity, and cognition. The endogenous secretion of glucocorticoids is normally characterized by a prominent and robust circadian (around 24 hours) oscillation, with a daily peak around the time of the habitual sleep-wake transition and minimal levels in the evening and early part of the night. It has been long recognized that this 24-h rhythm partly reflects the activity of a master circadian pacemaker located in the suprachiasmatic nucleus of the hypothalamus. In the past decade, secondary circadian clocks based on the same molecular machinery as the central master pacemaker were found in other brain areas as well as in most peripheral tissues, including the adrenal glands. Evidence is rapidly accumulating to indicate that misalignment between central and peripheral clocks has a host of adverse effects. The robust rhythm in circulating glucocorticoid levels has been recognized as a major i...

The Functional and Clinical Significance of the 24-Hour Rhythm of Circulating Glucocorticoids

Clock gene expression in the murine gastrointestinal tract: endogenous rhythmicity and effects of a feeding regimen.

https://www.gastrojournal.org/article/S0016-5085(08)01545-X/pdf

Transcriptional profiling of mRNA expression in the mouse distal colon.

Human bowel movements usually occur during the day and seldom during the night, suggesting a role for a biological clock in the regulation of colonic motility. Research has unveiled molecular and p...

Rhythmic changes in colonic motility are regulated by period genes

Diabetes may shift clock gene expression within peripheral organs. However, little is known about the effect of diabetes on the gastrointestinal molecular clock. We therefore investigated the effect of diabetes on gastrointestinal clock gene expression. As peripheral clock gene expression is strongly driven by food intake, we also determined the effect of STZ-induced diabetes on patterns of food intake. The effects of acute (1 week) and chronic (12 weeks) STZ-induced diabetes on period (per) genes in the stomach body, proximal and distal colon, liver, kidney, and lung of C57BL/6J mice were assessed using real-time polymerase chain reaction. Food intake studies were completed using automated feeding equipment. Rhythmicity in expression of per2 and per3 persisted in all organs. However, per2 and per3 expression of STZ-injected mice was generally phase delayed within the gastrointestinal tract but not within the kidney or lung as compared with vehicle-injected mice. The phase delay was most pronounced for per2 in the proximal colon at 12 weeks. Food intake was rhythmic with larger circadian amplitude for diabetic mice than for control mice. Thus, STZ-induced diabetes differentially alters peripheral per expression. STZ-induced diabetes does not alter the circadian phase of food intake. Alterations in clock gene expression in a mouse model of diabetes are most pronounced in those organs that are intimately associated with food processing and metabolism.

Jonathon Bostwick

Papers

Clock gene expression in the murine gastrointestinal tract: endogenous rhythmicity and effects of a feeding regimen.

Transcriptional profiling of mRNA expression in the mouse distal colon.

Rhythmic changes in colonic motility are regulated by period genes

Effects of acute and chronic STZ-induced diabetes on clock gene expression and feeding in the gastrointestinal tract.