Tag: circadian rhythm

Categories : ExerciseTags :

Fat Metabolism from Exercise Depends on Time of Day

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Exercise at the right time of the day may increase fat metabolism, at least according to the results of a mouse study. Published in the journal PNAS, research shows that mice that did exercise in an early active phase, which corresponds to morning exercise in humans, increased their metabolism more than mice that did exercise at a time usually spent resting.

Physical activity at different times of the day can affect the body in different ways since the biological processes depend on the circadian rhythms of the cells. To ascertain the effect of exercise timing on the burning of fat, researchers at Karolinska Institutet and the University of Copenhagen studied the adipose tissue of mice after a session of high-intensity exercise performed at two points of the daily cycle, an early active phase and early rest phase (corresponding to a late morning and late evening session, respectively, in humans). The researchers studied various markers for fat metabolism and analysed which genes were active in adipose tissue after exercise.

Independent of food intake

The researchers found that physical activity at an early active phase increased the expression of genes involved in the breakdown of adipose tissue, heat production and mitochondria in the adipose tissue, indicating a higher metabolic rate. These effects were observed only in mice that exercised in the early active phase and were independent of food intake.

“Our results suggest that late morning exercise could be more effective than late evening exercise in terms of boosting the metabolism and the burning of fat, and if this is the case, they could prove of value to people who are overweight,” says Professor Juleen R. Zierath at Karolinska Institutet.

Improving the health benefits of exercise

Mice and humans share many basic physiological functions, and mice are a well-established model for human physiology and metabolism. However, there are also important differences, such as the fact that mice are nocturnal.

“The right timing seems to be important to the body’s energy balance and to improving the health benefits of exercise, but more studies are needed to draw any reliable conclusions about the relevance of our findings to humans,” says Professor Zierath.

Source: Karolinska Institutet

Categories : Mental Health NeurologyTags :

Schizophrenia Associated with 12-hour Gene Cycles in the Brain

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In the open-access journal PLOS Biology, researchers present the first evidence of 12-hour cycles of gene activity in the human brain. Led by Madeline R. Scott, the study also reveals that some of those 12-hour rhythms are missing or altered in the postmortem brains of patients with schizophrenia.

Schizophrenia patients are known to have disturbances in several types of 24-hour bodily rhythms, including sleep/wake cycles, hormone levels, and gene activity in the prefrontal cortex of the brain. However, virtually nothing is known about gene activity in the brain for cycles that are shorter than the usual 24-hour circadian rhythm. A few years ago, researchers discovered that certain genes in the body were associated with 12-hour bodily rhythms, which may have an origin in the 12-hour cycle of ocean tides.

As it is not possible to measure gene transcript levels in living brains, the new study instead used a time-of-death analysis to search for 12-hour rhythms in gene activity within postmortem brains. They focused on the dorsolateral prefrontal cortex as it is associated with cognitive symptoms and other abnormalities in gene expression rhythms that have been observed in schizophrenia.

Numerous genes in the normal dorsolateral prefrontal cortex were found to have 12-hour rhythms in activity. Among them, gene activity levels related to building connections between neurons peaked in the afternoon/night, while those related to mitochondrial function (and therefore cellular energy supply) peaked in the morning/evening.

In contrast, postmortem brains from patients with schizophrenia contained fewer genes with 12-hour activity cycles, and those related to neural connections were missing entirely. Additionally, although the mitochondria-related genes did maintain a 12-hour rhythm, their activity did not peak at the normal times. Whether these abnormal rhythms underlie the behavioural abnormalities in schizophrenia, or whether they result from medications, nicotine use, or sleep disturbances should be examined in future studies.

Co-author Colleen A. McClung adds: “We find that the human brain has not only circadian (24 hour) rhythms in gene expression but also 12-hour rhythms in a number of genes that are important for cellular function and neuronal maintenance. Many of these gene expression rhythms are lost in people with schizophrenia, and there is a dramatic shift in the timing of rhythms in mitochondrial-related transcripts which could lead to suboptimal mitochondrial function at the times of day when cellular energy is needed the most.”

Source: ScienceDaily

Categories : HIVTags :

HIV Infection Creates Chronic ‘Jet Lag’ in Patients

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Research from South Africa and the UK has found that people living with HIV have a significantly delayed internal body clock, consistent with the symptoms of jet lag. The findings, which appear in the Journal of Pineal Research, may explain some of the health problems experienced by people with HIV, and guide research towards improving their quality of life.

Researchers from the University of the Witwatersrand and University of Cape Town along with Northumbria and Surrey universities in the UK and studied people aged 45 years and above living in Mpumalanga province, where nearly one in four people is living with HIV. As such, the infection is endemic and does not associate with any difference in lifestyle.

They found that physiological daily rhythms, as measured by the hormone melatonin, were delayed by more than an hour on average in HIV positive participants. Their sleep cycle was also shorter, with researchers noting that their sleep started later and finished earlier.

This suggests the possibility that HIV infection may cause a circadian rhythm disorder similar to the disruption experienced in shift work or jet lag.

The authors believe that this body clock disruption may contribute significantly to the increased burden of health problems that people living with HIV are experiencing despite successful treatment, such as an increased risk of cardiovascular, metabolic, and psychiatric disorders.

Researchers believe there is a strong need for further funding to identify whether similar disruption to the body clock is experienced by younger people living with HIV in other countries.

“The participants living with HIV essentially experience the one-hour disruption associated with switching to daylight savings time, but every single morning,” says corresponding author Malcolm von Schantz, Professor of Chronobiology at Northumbria University.

“This happens in spite of the fact that essentially everybody is exposed to the same light-dark cycle. Our findings have important potential implications for the health and wellbeing of people living with HIV, especially given the well-established relationships between disrupted circadian rhythms and sleep deprivation.”

Senior author Dr Karine Scheuermaier of Wits University added: “This is very similar to the risk profile observed in shift workers. Understanding and mitigating this disruption may be an important step towards helping people living with HIV live healthier lives.”

“Our findings identify an urgent research topic,” says Xavier Gómez-Olivé, also from the University of the Witwatersrand, whose research grant funded the study. “The next step must be to establish if the same body clock disruption exists in people living with HIV who are younger and who live in other countries.”

Co-author Dale Rae, of the University of Cape Town, added “This is a great example of the importance of studying sleep in people living in Africa, and demonstrates how findings from this research can also be relevant to people anywhere in the world.”

Source: Northumbria University

Categories : Metabolic DisordersTags :

How Late-night Eating Triggers Weight Gain and Diabetes

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Northwestern Medicine scientists have uncovered the mechanism behind why eating late at night is linked to weight gain and diabetes. The findings, published in the journal Science, may also help inform chronic care, especially with gastric feeding tubes.

Eating time, sleep and obesity have a well-known but poorly understood link, with research showing that over-nutrition can disrupt circadian rhythms and change fat tissue.

This new Northwestern University research has shown for the first time that energy release may be the molecular mechanism through which the body’s internal clocks control energy balance. From this understanding, the scientists also found that daytime is the ideal time in the light environment of the Earth’s rotation when it is most optimal to dissipate energy as heat. These findings have broad implications from dieting to sleep loss and the way we feed patients who require long-term nutritional assistance.

“It is well known, albeit poorly understood, that insults to the body clock are going to be insults to metabolism,” said corresponding study author Dr. Joseph T. Bass, a professor at Northwestern University Feinberg School of Medicine.

“When animals consume Western style cafeteria diets – high fat, high carb – the clock gets scrambled,” Dr Bass said. “The clock is sensitive to the time people eat, especially in fat tissue, and that sensitivity is thrown off by high-fat diets. We still don’t understand why that is, but what we do know is that as animals become obese, they start to eat more when they should be asleep. This research shows why that matters.”

Scrambling the internal clock

In the study, mice, who are nocturnal, were fed a high-fat diet either exclusively during their inactive (light) period or during their active (dark) period. Within a week, mice fed during light hours gained more weight compared to those fed in the dark. The team also set the temperature to 30 degrees, where mice expend the least energy, to mitigate the effects of temperature on their findings.

“We thought maybe there’s a component of energy balance where mice are expending more energy eating at specific times,” said first author Dr Chelsea Hepler, a postdoctoral fellow in Dr Bass’s lab. “That’s why they can eat the same amount of food at different times of the day and be healthier when they eat during active periods versus when they should be sleeping.”

The increase in energy expenditure led the team to look into metabolism of fat tissue to see if the same effect occurred within the endocrine organ. They found that it did, and mice with genetically enhanced thermogenesis prevented weight gain and improved health.

Dr Hepler also identified futile creatine cycling, in which creatine (a molecule that helps maintain energy) undergoes storage and release of chemical energy, within fat tissues, implying creatine may be the mechanism underlying heat release.

Intermittent fasting and gastric feeding tubes

The science is underpinned by research done by Dr Bass and colleagues at Northwestern more than 20 years ago that found a relationship between the internal molecular clock and body weight, obesity and metabolism in animals.

The challenge for Dr Bass’s lab, which focuses on using genetic approaches to study physiology, has been figuring out what it all means, and finding the control mechanisms that produce the relationship. This study brings them a step closer.

The findings could inform chronic care, Dr Bass said, especially in cases where patients have gastric feeding tubes. Patients are commonly fed at night while they sleep, when they’re releasing the least amount of energy. Rates of diabetes and obesity tend to be high for these patients, and Bass thinks this could explain why. He also wonders how the research could impact Type II Diabetes treatment. Should meal times be considered when insulin is given, for example?

Dr Hepler will continue to research creatine metabolism. “We need to figure out how, mechanistically, the circadian clock controls creatine metabolism so that we can figure out how to boost it,” she said. “Clocks are doing a lot to metabolic health at the level of fat tissue, and we don’t know how much yet.”

Source: Northwestern University

Categories : Metabolic DisordersTags :

Late Night Snacks Impact Hunger, Metabolism and Adipose Tissue

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While popular diets discourage midnight snacking, few studies have examined the simultaneous effects of late eating on the weight gain trifecta regulation of calorie intake, the number of calories burnt, and molecular changes in fat tissue. Now, a new study published in Cell Metabolism has found that timing of food intake significantly impacts energy expenditure, appetite, and molecular pathways in adipose tissue.

“We wanted to test the mechanisms that may explain why late eating increases obesity risk,” explained senior author Frank A. J. L. Scheer, PhD, Director of the Medical Chronobiology Program in the Brigham’s Division of Sleep and Circadian Disorders. “Previous research by us and others had shown that late eating is associated with increased obesity risk, increased body fat, and impaired weight loss success. We wanted to understand why.”

“In this study, we asked, ‘Does the time that we eat matter when everything else is kept consistent?'” said first author Nina Vujovic, PhD, a researcher in the Medical Chronobiology Program in the Brigham’s Division of Sleep and Circadian Disorders. “And we found that eating four hours later makes a significant difference for our hunger levels, the way we burn calories after we eat, and the way we store fat.”

Vujovic, Scheer and their team studied 16 patients with a body mass index (BMI) in the overweight or obese range. Each participant completed two laboratory protocols: one with a strictly scheduled early meal schedule, and the other with the exact same meals, each scheduled about four hours later in the day. In the last two to three weeks before starting each of the in-laboratory protocols, participants maintained fixed sleep and wake schedules, and in the final three days before entering the laboratory, they strictly followed identical diets and meal schedules at home. In the lab, participants regularly documented their hunger and appetite, provided frequent small blood samples throughout the day, and had their body temperature and energy expenditure measured. To measure how eating time affected molecular pathways involved in adipogenesis, or how the body stores fat, investigators collected biopsies of adipose tissue from a subset of participants during laboratory testing in both the early and late eating protocols, to enable comparison of gene expression patterns/levels between these two eating conditions.

Results revealed that eating later had profound effects on hunger and appetite-regulating hormones leptin and ghrelin, which influence our drive to eat. Specifically, levels of the hormone leptin, which signals satiety, were decreased across the 24 hours in the late eating condition compared to the early eating conditions. When participants ate later, they also burned calories at a slower rate and exhibited adipose tissue gene expression towards increased adipogenesis and decreased lipolysis, which promote fat growth. Notably, these findings convey converging physiological and molecular mechanisms underlying the correlation between late eating and increased obesity risk.

Vujovic explained that these findings are not only consistent with a large body of research suggesting that eating later increases risk of developing obesity, but they shed new light on how this might occur. By using a randomised crossover study, and tightly controlling for behavioural and environmental factors such as physical activity, posture, sleep, and light exposure, investigators were able to detect changes the different control systems involved in energy balance, a marker of how our bodies use the food we consume.

Future studies will include more female participants. Despite only five female participants, the study was set up to control for menstrual phase, reducing confounding but making recruiting women more difficult. Going forward, Scheer and Vujovic are also interested in better understanding the effects of the relationship between meal time and bedtime on energy balance.

“This study shows the impact of late versus early eating. Here, we isolated these effects by controlling for confounding variables like caloric intake, physical activity, sleep, and light exposure, but in real life, many of these factors may themselves be influenced by meal timing,” said Scheer. “In larger scale studies, where tight control of all these factors is not feasible, we must at least consider how other behavioural and environmental variables alter these biological pathways underlying obesity risk. “

Source: Brigham and Women’s Hospital

Categories : Environmental EffectsTags :

New Evidence-based Recommendations for Light Exposure

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For the first time, a set of recommendations have been drawn up to provide guidance for human exposure to light throughout the day and at nighttime, based on the amount of blue light in the environment. The recommendations are detailed in PLOS Biology.

Modern lifestyles, with 24-hour access to electric light and reduced exposure to natural daylight, can disrupt sleep and negatively impact health, well-being, and productivity. A new report in PLOS Biology addresses the issue of exactly how bright lighting should be during the day and in the evening to support healthy body rhythms, restful sleep, and daytime alertness.

An international body of leading scientific experts was brought together to draw up the first evidence-based, consensus recommendations for healthy daytime, evening, and nighttime light exposure. These recommendations provide much needed guidance to the lighting and electronics industries to aid the design of healthier environments and to improve how we light our workplaces, public buildings, and homes.

The new report took on a key question – how to properly measure the extent to which different types of lighting might influence circadian rhythms and sleep patterns. Light affects these patterns via a specialised type of cell in the eye that uses a light sensitive protein, melanopsin, that is distinct from the opsin in the rods and cones that support vision (and upon which traditional ways of measuring “brightness” are based). Since melanopsin is most sensitive to blue-cyan light, the new recommendations used a newly-developed light measurement standard tailored to this unique property: melanopic equivalent daylight illuminance. Analysis of data from a variety of studies proved that this new measurement approach could provide a reliable way of predicting the effects of light on human physiology and body rhythms, and so could form the basis of widely applicable and meaningful recommendations.

A crucial next step will be to integrate the recommendations into formal lighting guidelines, which currently focus on visual requirements rather than effects on health and well-being. Additionally, advances in LED lighting technology and the availability of low-cost light sensors are expected to increase the ease with which individuals can optimise their personal light exposure to best support their own circadian rhythms in line with the new recommendations.

Professor Timothy Brown, who brought the international exports together for the report added: “These recommendations provide the first scientific consensus, quantitative, guidance for appropriate daily patterns of light exposure to support healthy body rhythms, nighttime sleep and daytime alertness. This now provides a clear framework to inform how we light any interior space ranging from workplaces, educational establishments and healthcare facilities to our own homes.”

Source: Science Daily

Categories : COVIDTags :

COVID Test Sensitivity Changes with Circadian Rhythm

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A new study suggests that the sensitivity of tests for SARS-CoV-2 vary throughout the day according to the body’s circadian rhythm, which could have implications for how the disease is managed.

Carl Johnson, Cornelius Vanderbilt Professor of Biological Sciences, wondered how the virus might act differently depending on the time of day and the body’s circadian rhythms, and collaborated with colleagues to determine if the percentage of people testing positive for COVID varies based on time of day. They found that people were up to two times as likely to have an accurate positive test result if they tested in the middle of the day compared to at night. Their findings were published in the Journal of Biological Rhythms.

The data support the hypothesis that COVID acts differently in the body based on our natural circadian rhythm, which has also been implied by studies of other viral and bacterial infections. COVID virus shedding, when infected cells release infectious virus particles into the blood and mucus, appears to be more active around midday due to modulation of the immune system by our biological clock.

“Taking a COVID test at the optimal time of day improves test sensitivity and will help us to be accurate in diagnosing people who may be infected but asymptomatic,” Prof Johnson said. Their results indicate that viral load is lower after 8 pm. If people choose to get tested at that time, there could be a higher chance of a false-negative result. False negatives can be harmful to the community and for the patient, who might not seek additional care due to their negative test result.

A difference in COVID viral shedding throughout the day would help inform treatment for the disease. As Johnson and his co-authors report, the peak shedding in the afternoon, when patients are more likely to interact with others or seek medical care, could play a role in increasing the spread of the virus in hospitals and the wider community.

Further research is needed to confirm the diurnal nature of SARS-CoV-2. Experimentally testing COVID patients to see if individuals shed the virus differently throughout the day would have important public health implications, Prof Johnson said.

Source: Vanderbilt University

Categories : Medical Research & TechnologyTags :

Muscles are Timekeepers for the Liver

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Researchers have found that skeletal muscles play a large part in regulating the liver’s biological clock. The findings were published in Science Advances.

The circadian rhythm is coordinated by the brain at a general level, but each organ or tissue is also subjected to specific regulation, adjusting to time to optimise their processes. However it was not known how the liver “knows” whether it is day or night.

The liver’s main role is digestion, mainly of fats and sugars: the brain is the main consumer of sugar while skeletal muscle is the main consumer of fat.

Scientists at IRB Barcelona discovered a surprising relationship: that it is skeletal muscle which regulates liver function and determines fat metabolism. Skeletal muscle accomplishes this by secreting a that is transported to the liver through serum is responsible for modulating around 35% of the metabolic functions of the liver. The remaining basal functions of this organ and others related to carbohydrate metabolism are independent of muscle activity and are regulated by the basal circadian rhythm from the brain.

“It’s a very nice discovery because it is the first demonstration of the need for communication between the circadian clocks of tissues and organs outside the brain, and we can see that this communication between muscle and liver is altered by aging,” said study leader Dr Salvador Aznar-Benitah at IRB Barcelona. “When we get older, cells stop obeying the biological clock and begin to perform functions in a non-optimal manner, leading to errors that cause tissues to age.”

The researcher’s results show that the liver does not independently regulate the metabolism of fats and that it is muscle that sends the message that it is time to switch on fatty acid metabolism and how it should go about this. “We didn’t expect to find this connection between the liver and muscle because it wasn’t known previously, but, on second thought, it makes complete sense that fat management is coordinated by one of its main consumers,” said Dr Aznar-Benitah. Carbohydrate metabolism meanwhile is dependent on the basal coordination exercised by the brain.

Source: Institute for Research in Biomedicine (IRB Barcelona)

Categories : Diet and Nutrition Metabolic DisordersTags :

Body Clock Disruption on High-fat Diet Leads to Obesity

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According to a new study, when rats are fed a high fat diet, this disturbs the body clock in their brain that normally controls satiety, leading to over-eating and obesity. 

This new research, published in the Journal of Physiology, may be a cornerstone for future clinical studies that could restore the proper functioning of the body clock in the brain, to avoid overeating.

It was believed that the body clock resided only in the hypothalamus, but research over the years has clarified that some control of our body’s daily rhythms (hormone levels, appetite etc) lies in several other parts of the brain and body, including a group of neurons in the evolutionary ancient brainstem, called the dorsal vagal complex (DVC).

Specifically, the DVC has been shown to moderate food intake by inducing satiety. In obesity, research has shown that daily rhythms in food intake and the release of hormones related to eating, are blunted or eliminated. It is unclear if the malfunctioning of brain centres controlling appetite is a cause or the result of obesity.

This new study found that rats on a high-fat diet, before they started to gain weight, showed changes in the DVC’s daily neuronal rhythms and its response to appetite hormones. Thus, the researchers proposed that DVC disruption causes obesity.

Two groups of rats were used: those fed a well-balanced control diet (10% kcal from fat) and a high-fat diet (70% kcal from fat). To mimic the impact of unhealthy diet on humans, the researchers introduced the new diet to adolescent rats and monitored their food intake over 24h for four weeks.

Using multi-electrode arrays, the researchers measured DVC changes over 24h, simultaneously monitoring around a hundred DVC neurons from each brainstem slice. With this, circadian changes of neuronal activity could be assessed as well as neuronal responses to metabolically-relevant hormones in each of the diet groups.

Rats being nocturnal animals is a limitation of the study. The DVC activity peaked at the end of day, the rest phase for rodents, but an active phase for humans. Thus, it remains to be established if the phase of the brainstem clock is set to day and night, or whether it depends on patterns of rest and activity. These findings however could lead to understanding how to reset the body clock and tackle obesity.

First author Dr Lukasz Chrobok said:

“I’m really excited about this research because of the possibilities it opens up to tackle the growing health issue of obesity. We still do not know what are the time cues which are able to reset or synchronise the brainstem clock. Hopefully, the restoration of daily rhythms in this satiety centre before or after the onset of obesity may provide new therapeutic opportunities.”

Source: The Physiological Society

Categories : Respiratory DiseasesTags :

Circadian Rhythm Contributes to Asthma Severity

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By pinning down the influence of the circadian system on nocturnal asthma, researchers have uncovered a key role for the biological clock in asthma.

Asthma severity has long been observed to worsen in the nighttime. Lung function is highest at around 4pm and worst around 4am. One longstanding question has been to what degree the body’s internal circadian clock contributes to worsening of asthma severity, as opposed to behaviours such as sleep. Using two circadian protocols, researchers have delineated the influence of the circadian system. Understanding the mechanisms behind asthma severity could have important implications for both studying and treating asthma. 

“This is one of the first studies to carefully isolate the influence of the circadian system from the other factors that are behavioral and environmental, including sleep,” said co-corresponding author Frank AJL Scheer, PhD, director of the Medical Chronobiology Program in the Division of Sleep and Circadian Disorders at the Brigham.

As many as 75 percent of people with asthma report experiencing worsening asthma severity at night. Asthma severity is influenced by behavioural and environmental factors, such as exercise, air temperature, posture, and sleep environment. The researcher sought to understand the internal circadian system’s contributions to this problem. The circadian system is composed of a central pacemaker in the brain (the suprachiasmatic nucleus) and “clocks” throughout the body and is critical for the coordination of bodily functions and to anticipate the daily cycling environmental and behavioral demands.

To isolate the influence of the circadian system from that of sleep and other behavioural and environmental factors, the researchers enrolled 17 participants with asthma into two complementary laboratory protocols where lung function, asthma symptoms and bronchodilator use were continuously assessed. In the “constant routine” protocol, participants spent 38 hours continuously awake, in a constant posture, and under dim light conditions, with identical snacks every two hours. In the “forced desynchrony” protocol, participants were placed on a recurring 28-hour sleep/wake cycle for a week under dim light conditions, with all behaviours scheduled evenly across the cycle.

Co-corresponding author Steven A. Shea, Ph.D., professor and director at Oregon Institute of Occupational Health Sciences said, “We observed that those people who have the worst asthma in general are the ones who suffer from the greatest circadian-induced drops in pulmonary function at night, and also had the greatest changes induced by behaviours, including sleep. We also found that these results are clinically important because, when studied in the laboratory, symptom-driven bronchodilator inhaler use was as much as four times more often during the circadian night than during the day.”  

The study was published in Proceedings of the National Academy of Sciences.

Source: Medical Xpress