Chronotype: Implications for Epidemiologic Studies on Chrono-Nutrition and Cardiometabolic Health.

Chrono-nutrition is an emerging research field in nutritional epidemiology that encompasses 3 dimensions of eating behavior: timing, frequency, and regularity. To date, few studies have investigated how an individual's circadian typology, i.e., one's chronotype, affects the association between chrono-nutrition and cardiometabolic health. This review sets the directions for future research by providing a narrative overview of recent epidemiologic research on chronotype, its determinants, and its association with dietary intake and cardiometabolic health. Limited research was found on the association between chronotype and dietary intake in infants, children, and older adults. Moreover, most of the evidence in adolescents and adults was restricted to cross-sectional surveys with few longitudinal cohorts simultaneously collecting data on chronotype and dietary intake. There was a gap in the research concerning the association between chronotype and the 3 dimensions of chrono-nutrition. Whether chronotype modifies the association between diet and cardiometabolic health outcomes remains to be elucidated. In conclusion, further research is required to understand the interplay between chronotype, chrono-nutrition, and cardiometabolic health outcomes

Cross-regulatory circuits linking inflammation, high-fat diet, and the circadian clock

Mammalian physiology resonates with the daily changes in the external environment, allowing processes such as rest-activity cycles, metabolism, and body temperature to synchronize with daily changes in the surroundings. Studies have identified the molecular underpinnings of robust oscillations in gene expression occurring over the 24-h day, but how acute or chronic perturbations modulate gene expression rhythms, physiology, and behavior is still relatively unknown. In this issue of Genes & Development, Hong and colleagues (pp. 1367-1379) studied how acute and chronic inflammation interacts with the circadian clock. They found that NF-kappa B signaling can modify chromatin states and modulate expression of genes in the core clock network as well as circadian locomotor behavior. Interestingly, a high-fat diet (HFD) fed to mice also triggers this inflammation pathway, suggesting that cross-regulatory circuits link inflammation, HFD, and the circadian clock

The genomic landscape of human cellular circadian variation points to a novel role for the signalosome

The importance of natural gene expression variation for human behavior is undisputed, but its impact on circadian physiology remains mostly unexplored. Using umbilical cord fibroblasts, we have determined by genome-wide association how common genetic variation impacts upon cellular circadian function. Gene set enrichment points to differences in protein catabolism as one major source of clock variation in humans. The two most significant alleles regulated expression of COPS7B, a subunit of the COP9 signalosome. We further show that the signalosome complex is imported into the nucleus in timed fashion to stabilize the essential circadian protein BMAL1, a novel mechanism to oppose its proteasome-mediated degradation. Thus, circadian clock properties depend in part upon a genetically-encoded competition between stabilizing and destabilizing forces, and genetic alterations in these mechanisms provide one explanation for human chronotype

At the Intersection of Microbiota and Circadian Clock: Are Sexual Dimorphism and Growth Hormones the Missing Link to Pathology? Circadian Clock and Microbiota: Potential Egffect on Growth Hormone and Sexual Development

Reciprocal interactions between the host circadian clock and the microbiota are evidenced by recent literature. Interestingly, dysregulation of either the circadian clock or microbiota is associated with common human pathologies such as obesity, type 2 diabetes, or neurological disorders. However, it is unclear to what extent a perturbation of pathways regulated by both the circadian clock and microbiota is involved in the development of these disorders. It is speculated that these perturbations are associated with impaired growth hormone (GH) secretion and sexual development. The GH axis is a broadly neglected pathway and could be the main converging point for the interaction of both circadian clock and microbiota. Here, the links between the circadian clock and microbiota are reviewed. Finally, the effects of chronodisruption and dysbiosis on physiology and pathology are discussed and it is speculated whether a common deregulation of the GH pathway could mediates those effects

Chronopharmacology: New insights and therapeutic implications

Most facets of mammalian physiology and behavior vary according to time of day, thanks to endogenous circadian clocks. Therefore, it is not surprising that many aspects of pharmacology and toxicology also oscillate according to the same 24-h clocks. Daily oscillations in abundance of proteins necessary for either drug absorption or metabolism result in circadian pharmacokinetics, and oscillations in the physiological systems targeted by these drugs result in circadian pharmacodynamics. These clocks are present in most cells of the body, organized in a hierarchical fashion. Interestingly, some aspects of physiology and behavior are controlled directly via a "master clock" in the suprachiasmatic nuclei of the hypothalamus, whereas others are controlled by "slave" oscillators in separate brain regions or body tissues. Recent research shows that these clocks can respond to different cues and thereby show different phase relationships. Therefore, full prediction of chronopharmacology in pathological contexts will likely require a systems biology approach that considers chronointeractions among different clock-regulated systems. Expected final online publication date for the Annual Review of Pharmacology and Toxicology Volume 54 is January 06, 2014. Please see http://www.annualreviews.org/catalog/pubdates.aspx for revised estimates

Proteomics and circadian rhythms: It's all about signaling!

Proteomic technologies using MS offer new perspectives in circadian biology, in particular the possibility to study PTMs. To date, only very few studies have been carried out to decipher the rhythmicity of protein expression in mammals with large-scale proteomics. Although signaling has been shown to be of high relevance, comprehensive characterization studies of PTMs are even more rare. This review aims at describing the actual landscape of circadian proteomics and the opportunities and challenges appearing on the horizon. Emphasis was given to signaling processes for their role in metabolic health as regulated by circadian clocks and environmental factors. Those signaling processes are expected to be better and more deeply characterized in the coming years with proteomics

Regulation of Mammalian Physiology by interconnected Circadian and Feeding Rhythms

Circadian clocks are endogenous timekeeping systems that adapt in an anticipatory fashion the physiology and behavior of most living organisms. In mammals, the master pacemaker resides in the suprachiasmatic nucleus and entrains peripheral clocks using a wide range of signals that differentially schedule physiology and gene expression in a tissue-specific manner. The peripheral clocks, such as those found in the liver, are particularly sensitive to rhythmic external cues like feeding behavior, which modulate the phase and amplitude of rhythmic gene expression. Consequently, the liver clock temporally tunes the expression of many genes involved in metabolism and physiology. However, the circadian modulation of cellular functions also relies on multiple layers of posttranscriptional and posttranslational regulation. Strikingly, these additional regulatory events may happen independently of any transcriptional oscillations, showing that complex regulatory networks ultimately drive circadian output functions. These rhythmic events also integrate feeding-related cues and adapt various metabolic processes to food availability schedules. The importance of such temporal regulation of metabolism is illustrated by metabolic dysfunctions and diseases resulting from circadian clock disruption or inappropriate feeding patterns. Therefore, the study of circadian clocks and rhythmic feeding behavior should be of interest to further advance our understanding of the prevention and therapy of metabolic diseases.UPNA

Glucose Homeostasis: Regulation by Peripheral Circadian Clocks in Rodents and Humans

Most organisms, including humans, have developed an intrinsic system of circadian oscillators, allowing the anticipation of events related to the rotation of Earth around its own axis. The mammalian circadian timing system orchestrates nearly all aspects of physiology and behavior. Together with systemic signals, emanating from the central clock that resides in the hypothalamus, peripheral oscillators orchestrate tissue-specific fluctuations in gene expression, protein synthesis, and posttranslational modifications, driving overt rhythms in physiology and behavior. There is increasing evidence on the essential roles of the peripheral oscillators, operative in metabolically active organs in the regulation of body glucose homeostasis. Here, we review some recent findings on the molecular and cellular makeup of the circadian timing system and its implications in the temporal coordination of metabolism in health and disease