Circadian Timing of Food Intake Contributes to Weight Gain

Studies of body weight regulation have focused almost entirely on caloric intake and energy expenditure. However, a number of recent studies in animals linking energy regulation and the circadian clock at the molecular, physiological, and behavioral levels raise the possibility that the timing of food intake itself may play a significant role in weight gain. The present study focused on the role of the circadian phase of food consumption in weight gain. We provide evidence that nocturnal mice fed a high‐fat diet only during the 12‐h light phase gain significantly more weight than mice fed only during the 12‐h dark phase. A better understanding of the role of the circadian system for weight gain could have important implications for developing new therapeutic strategies for combating the obesity epidemic facing the human population today

Electronic Abstracts - Art for the Space Age

New forms and techniques of art for the space age may involve physical forces and ideas, as well as materials and procedures from technology. Such a new approach to abstract design is that shown here in the electronic abstractions or oscillons

Oscillons: an encounter with dynamical chaos in 1953?

We present evidences that Ben F. Laposky (1914-2000) might have been the first person who created a family of nonlinear analog circuits that allowed him to observe chaotic attractors and other trademarks of nonlinear science as early as 1953.Comment: accepted to Chao

Uncovering the Genetic Landscape for Multiple Sleep-Wake Traits

Despite decades of research in defining sleep-wake properties in mammals, little is known about the nature or identity of genes that regulate sleep, a fundamental behaviour that in humans occupies about one-third of the entire lifespan. While genome-wide association studies in humans and quantitative trait loci (QTL) analyses in mice have identified candidate genes for an increasing number of complex traits and genetic diseases, the resources and time-consuming process necessary for obtaining detailed quantitative data have made sleep seemingly intractable to similar large-scale genomic approaches. Here we describe analysis of 20 sleep-wake traits from 269 mice from a genetically segregating population that reveals 52 significant QTL representing a minimum of 20 genomic loci. While many (28) QTL affected a particular sleep-wake trait (e.g., amount of wake) across the full 24-hr day, other loci only affected a trait in the light or dark period while some loci had opposite effects on the trait during the light vs. dark. Analysis of a dataset for multiple sleep-wake traits led to previously undetected interactions (including the differential genetic control of number and duration of REM bouts), as well as possible shared genetic regulatory mechanisms for seemingly different unrelated sleep-wake traits (e.g., number of arousals and REM latency). Construction of a Bayesian network for sleep-wake traits and loci led to the identification of sub-networks of linkage not detectable in smaller data sets or limited single-trait analyses. For example, the network analyses revealed a novel chain of causal relationships between the chromosome 17@29cM QTL, total amount of wake, and duration of wake bouts in both light and dark periods that implies a mechanism whereby overall sleep need, mediated by this locus, in turn determines the length of each wake bout. Taken together, the present results reveal a complex genetic landscape underlying multiple sleep-wake traits and emphasize the need for a systems biology approach for elucidating the full extent of the genetic regulatory mechanisms of this complex and universal behavior

Circadian clock proteins regulate neuronal redox homeostasis and neurodegeneration

Brain aging is associated with diminished circadian clock output and decreased expression of the core clock proteins, which regulate many aspects of cellular biochemistry and metabolism. The genes encoding clock proteins are expressed throughout the brain, though it is unknown whether these proteins modulate brain homeostasis. We observed that deletion of circadian clock transcriptional activators aryl hydrocarbon receptor nuclear translocator–like (Bmal1) alone, or circadian locomotor output cycles kaput (Clock) in combination with neuronal PAS domain protein 2 (Npas2), induced severe age-dependent astrogliosis in the cortex and hippocampus. Mice lacking the clock gene repressors period circadian clock 1 (Per1) and period circadian clock 2 (Per2) had no observed astrogliosis. Bmal1 deletion caused the degeneration of synaptic terminals and impaired cortical functional connectivity, as well as neuronal oxidative damage and impaired expression of several redox defense genes. Targeted deletion of Bmal1 in neurons and glia caused similar neuropathology, despite the retention of intact circadian behavioral and sleep-wake rhythms. Reduction of Bmal1 expression promoted neuronal death in primary cultures and in mice treated with a chemical inducer of oxidative injury and striatal neurodegeneration. Our findings indicate that BMAL1 in a complex with CLOCK or NPAS2 regulates cerebral redox homeostasis and connects impaired clock gene function to neurodegeneration

A genome-wide association study of sleep habits and insomnia

Several aspects of sleep behavior such as timing, duration and quality have been demonstrated to be heritable. To identify common variants that influence sleep traits in the population, we conducted a genome-wide association study of six sleep phenotypes assessed by questionnaire in a sample of 2,323 individuals from the Australian Twin Registry. Genotyping was performed on the Illumina 317, 370, and 610K arrays and the SNPs in common between platforms were used to impute non-genotyped SNPs. We tested for association with more than 2,000,000 common polymorphisms across the genome. While no SNPs reached the genome-wide significance threshold, we identified a number of associations in plausible candidate genes. Most notably, a group of SNPs in the third intron of the CACNA1C gene ranked as most significant in the analysis of sleep latency (P=1.3×10-6). We attempted to replicate this association in an independent sample from the Chronogen Consortium (n=2,034), but found no evidence of association (P=0.73). We have identified several other suggestive associations that await replication in an independent sample. We did not replicate the results from previous genome-wide analyses of self-reported sleep phenotypes after correction for multiple testing

Female Sex and Gender in Lung/Sleep Health and Disease. Increased Understanding of Basic Biological, Pathophysiological, and Behavioral Mechanisms Leading to Better Health for Female Patients with Lung Disease

Female sex/gender is an undercharacterized variable in studies related to lung development and disease. Notwithstanding, many aspects of lung and sleep biology and pathobiology are impacted by female sex and female reproductive transitions. These may manifest as differential gene expression or peculiar organ development. Some conditions are more prevalent in women, such as asthma and insomnia, or, in the case of lymphangioleiomyomatosis, are seen almost exclusively in women. In other diseases, presentation differs, such as the higher frequency of exacerbations experienced by women with chronic obstructive pulmonary disease or greater cardiac morbidity among women with sleep-disordered breathing. Recent advances in -omics and behavioral science provide an opportunity to specifically address sex-based differences and explore research needs and opportunities that will elucidate biochemical pathways, thus enabling more targeted/personalized therapies. To explore the status of and opportunities for research in this area, the NHLBI, in partnership with the NIH Office of Research on Women's Health and the Office of Rare Diseases Research, convened a workshop of investigators in Bethesda, Maryland on September 18 and 19, 2017. At the workshop, the participants reviewed the current understanding of the biological, behavioral, and clinical implications of female sex and gender on lung and sleep health and disease, and formulated recommendations that address research gaps, with a view to achieving better health outcomes through more precise management of female patients with nonneoplastic lung disease. This report summarizes those discussions

Body weight, metabolism and clock genes

Biological rhythms are present in the lives of almost all organisms ranging from plants to more evolved creatures. These oscillations allow the anticipation of many physiological and behavioral mechanisms thus enabling coordination of rhythms in a timely manner, adaption to environmental changes and more efficient organization of the cellular processes responsible for survival of both the individual and the species. Many components of energy homeostasis exhibit circadian rhythms, which are regulated by central (suprachiasmatic nucleus) and peripheral (located in other tissues) circadian clocks. Adipocyte plays an important role in the regulation of energy homeostasis, the signaling of satiety and cellular differentiation and proliferation. Also, the adipocyte circadian clock is probably involved in the control of many of these functions. Thus, circadian clocks are implicated in the control of energy balance, feeding behavior and consequently in the regulation of body weight. In this regard, alterations in clock genes and rhythms can interfere with the complex mechanism of metabolic and hormonal anticipation, contributing to multifactorial diseases such as obesity and diabetes. The aim of this review was to define circadian clocks by describing their functioning and role in the whole body and in adipocyte metabolism, as well as their influence on body weight control and the development of obesity

Seasonal Changes in Mood and Behavior Are Linked to Metabolic Syndrome

BACKGROUND: Obesity is a major public health problem worldwide. Metabolic syndrome is a risk factor to the cardiovascular diseases. It has been reported that disruptions of the circadian clockwork are associated with and may predispose to metabolic syndrome. METHODOLOGY AND PRINCIPAL FINDINGS: 8028 individuals attended a nationwide health examination survey in Finland. Data were collected with a face-to-face interview at home and during an individual health status examination. The waist circumference, height, weight and blood pressure were measured and samples were taken for laboratory tests. Participants were assessed using the ATP-III criteria for metabolic syndrome and with the Seasonal Pattern Assessment Questionnaire for their seasonal changes in mood and behavior. Seasonal changes in weight in particular were a risk factor of metabolic syndrome, after controlling for a number of known risk and potential confounding factors. CONCLUSIONS AND SIGNIFICANCE: Metabolic syndrome is associated with high global scores on the seasonal changes in mood and behavior, and with those in weight in particular. Assessment of these changes may serve as a useful indicator of metabolic syndrome, because of easy assessment. Abnormalities in the circadian clockwork which links seasonal fluctuations to metabolic cycles may predispose to seasonal changes in weight and to metabolic syndrome