Researchers at Uppsala University recently demonstrated that one night of sleep loss has a tissue-specific impact on the regulation of gene expression and metabolism in humans. This may explain how shift work and chronic sleep loss impairs our metabolism and adversely affects our body composition. The study is published in the scientific journal Science Advances.
Epidemiological studies have shown that the risk for obesity and type 2 diabetes is elevated in those who suffer from chronic sleep loss or who carry out shift work. Other studies have shown an association between disrupted sleep and adverse weight gain, in which fat accumulation is increased at the same time as muscle mass is reduced - a combination that in and of itself has been associated with numerous adverse health consequences. Researchers from Uppsala and other groups have in earlier studies shown that metabolic functions that are regulated by e.g. skeletal muscle and adipose tissue are adversely affected by disrupted sleep and circadian rhythms. However, until now it has remained unknown whether sleep loss per se can cause molecular changes at the tissue level that can confer an increased risk of adverse weight gain.
The researchers studied 15 healthy normal-weight individuals who participated in two in-lab sessions in which activity and meal patterns were highly standardized. In randomized order, the participants slept a normal night of sleep - over eight hours - during one session, and were instead kept awake the entire night during the other session. The morning after each night-time intervention, small tissue samples or biopsies were taken from the participants' subcutaneous fat and skeletal muscle. These two tissues often exhibit disrupted metabolism in conditions such as obesity and diabetes. At the same time in the morning, blood samples were also taken to enable a comparison across tissue compartments of a number of metabolites. These metabolites comprise sugar molecules, as well as different fatty and amino acids.
The tissue samples were used for multiple molecular analyses, which first of all revealed that the sleep loss condition resulted in a tissue-specific change in DNA methylation, one form of mechanism that regulates gene expression. DNA methylation is a so-called epigenetic modification that is involved in regulating how the genes of each cell in the body are turned on or off, and is impacted by both hereditary as well as environmental factors, such as physical exercise. This research group was the first to demonstrate that acute sleep loss in and of itself results in epigenetic changes in the so-called clock genes that within each tissue regulate its circadian rhythm. These new findings indicate that sleep loss causes tissue-specific changes to the degree of DNA methylation in genes spread throughout the human genome.
Sleep Loss Results
“Our parallel analysis of both muscle and adipose tissue further enabled us to reveal that DNA methylation is not regulated similarly in these tissues in response to acute sleep loss," says Jonathan Cedernaes who led the study. "It is interesting that we saw changes in DNA methylation only in adipose tissue, and specifically for genes that have also been shown to be altered at the DNA methylation level in metabolic conditions such as obesity and type 2 diabetes. Epigenetic modifications are thought to be able to confer a sort of metabolic "memory" that can regulate how metabolic programs operate over longer time periods. We therefore think that the changes we have observed in our new study can constitute another piece of the puzzle of how chronic disruption of sleep and circadian rhythms may impact the risk of developing for example obesity."
Further analyses of gene and protein expression demonstrated that the response as a result of wakefulness differed between skeletal muscle and adipose tissue. The researchers say that the period of wakefulness simulates the overnight wakefulness period of many shift workers assigned to night work. A possible explanation for why the two tissues respond in the observed manner could be that overnight wakefulness periods exert a tissue-specific effect on tissues' circadian rhythm, resulting in misalignment between these rhythms.
This is something that the researchers found preliminary support for also in this study, as well as in an earlier similar but smaller study. "In the present study we observed molecular signatures of increased inflammation across tissues in response to sleep loss,” Cedernaes said. “However, we also saw specific molecular signatures that indicate that the adipose tissue is attempting to increase its capacity to store fat following sleep loss, whereas we instead observed signs indicating concomitant breakdown of skeletal muscle proteins in the skeletal muscle, in what's also known as catabolism. We also noted changes in skeletal muscle levels of proteins involved handling blood glucose, and this could help explain why the participants' glucose sensitivity was impaired following sleep loss. Taken together, these observations may provide at least partial mechanistic insight as to why chronic sleep loss and shift work can increase the risk of adverse weight gain as well as the risk of type 2 diabetes."
The researchers have only studied the effect of one night of sleep loss, and therefore do not know how other forms of sleep or disruption of circadian misalignment would have affected the participants' tissue metabolism. "It will be interesting to investigate to what extent one or more nights of recovery sleep can normalize the metabolic changes that we observe at the tissue level as a result of sleep loss,” Cedernaes added. “Diet and exercise are factors that can also alter DNA methylation, and these factors can thus possibly be used to counteract adverse metabolic effects of sleep loss."
Link Between Fruit Juice Consumption And Weight Gain
Another recent study that analyzed data from more than 49,000 women concludes that drinking 100 percent fruit juice leads to weight gain, while consumption of fresh whole fruit results in weight loss. The study - led by Brandon Auerbach, MD, MPH, an internal medicine and primary care physician at Virginia Mason Medical Center - was posted online by Preventive Medicine. “American adults gain an average of one pound per year, and it is a public health priority to determine which foods and beverages contribute the most to this gradual weight gain,” the report states. Specifically, this study analyzed data from 49,106 women in the United States enrolled in the Women’s Health Initiative between 1993 and 1998. Food-frequency questionnaires assessed food and beverage consumption, while their body weight was measured during in-person clinic visits.
The study found that an increase of one six-ounce serving of 100 percent fruit juice per day was associated with a modest amount of long-term weight gain. The average weight gain of 0.4 pounds or 6.4 ounces per person over three years was similar to two earlier published studies on this topic. This amount of weight gain was also similar to weight gain associated with increasing regular soda consumption - 0.6 pounds or 9.6 ounces. On the other hand, increasing consumption of whole fruit by one serving per day resulted in the loss of 0.9 pounds or 14.4 ounces over three years. “It is biologically plausible that drinking 100 percent fruit juice is associated with long-term weight gain,” the study concludes. “One six-ounce serving of 100 percent fruit juice contains 15 to 30 grams of sugar, 60 to 120 calories, little or no dietary fiber, and has a moderately high glycemic load. Even high-pulp, 100 percent orange juice is not a significant source of dietary fiber.”
The study’s findings support recommendations of the "2015-2020 Dietary Guidelines for Americans" that individuals should drink 100 percent fruit juice in moderation and choose whole fruits over fruit juice when possible. The guidelines are published by the U.S. Department of Health and Human Services and the U.S. Department of Agriculture. “Adults should have at least two servings of fruit a day, ideally more,” Dr. Auerbach said. “Even though 100 percent fruit juice has lots of vitamins, minerals and nutrients like antioxidants, it’s really better to get your daily fruit in the form of whole fruit. Especially for adults trying to lose weight, 100 percent fruit juice is not your friend.”
Winter Weight Gain Explained
A breakthrough study by University of Alberta researchers has shown the fat cells that lie just beneath our skin shrink when exposed to the blue light emitted by the sun. "When the sun's blue light wavelengths - the light we can see with our eye - penetrate our skin and reach the fat cells just beneath, lipid droplets reduce in size and are released out of the cell,” says Peter Light, senior author of the study and a professor of pharmacology and the director of UAlberta's Alberta Diabetes Institute. “In other words, our cells don't store as much fat. If you flip our findings around, the insufficient sunlight exposure we get eight months of the year living in a northern climate may be promoting fat storage and contribute to the typical weight gain some of us have over winter."
Light cautions the finding is only an initial observation and that pursuing exposure to sunlight is not a safe or recommended way to lose weight. "For example, we don't yet know the intensity and duration of light necessary for this pathway to be activated," Light added. “However, the novel discovery opens up new avenues of future scientific exploration which could someday lead to pharmacological or light-based treatments for obesity and other related health issues such as diabetes. Maybe this mechanism contributes to setting the number of fat cells we produce in childhood - thought to stay with us into adulthood. Obviously, there is a lot of literature out there suggesting our current generation will be more overweight than their parents and maybe this feeds into the debate about what is healthy sunshine exposure."
The researchers made the discovery while investigating how to bioengineer fat cells to produce insulin in response to light to help Type 1 diabetes patients. "It was serendipitous," said Light. "We noticed the reaction in human tissue cells in our negative control experiments, and since there was nothing in the literature, we knew it was important to investigate further."
Based on the finding, the fat cells we store near our skin may be a peripheral biological clock. "It's early days, but it's not a giant leap to suppose that the light that regulates our circadian rhythm, received through our eyes, may also have the same impact through the fat cells near our skin," Light added. He explained that the molecular pathway they discovered was first identified as being activated by the eye when exposed to the blue wavelengths in sunlight. "That's why you are not supposed to look at digital devices before bed because they emit the same blue light the sun does, that signals us to wake up," he said. "Well, perhaps that pathway - exposure to sunlight that directs our sleep-wake patterns - may also act in a sensory manner, setting the amount of fat humans burn depending on the season. You gain weight in the winter, and then burn it off in the summer."
This could be evolutionary process, supported by the fact that unlike many other mammals, our fat is spread out all over our bodies just underneath our skin. "Our initial first observation certainly holds many fascinating clues for our team and others around the world to explore," Light said.
Fatty Heart Linked To Race, Type Of Weight Gain
A woman’s race and where on her body she packs on pounds at midlife could give her doctor valuable clues to her likelihood of having greater volumes of heart fat, a potential risk factor for heart disease, according to research led by the University of Pittsburgh Graduate School of Public Health.
The findings - published in the journal Menopause - show that black women who put on fat around their midsection during midlife are more likely to accumulate fat around their hearts, whereas white women’s risk of fatty hearts is higher when they add weight all over. The results echo the findings of a Pitt Public Health study three years ago in men. “Excess fat around the heart, in both men and women, is an evolving risk factor for heart disease. But how can clinicians see it at a regular physical? They can’t without a special heart scan,” said senior author Samar El Khoudary, Ph.D., M.P.H., associate professor of epidemiology at Pitt Public Health. “This study, coupled with our previous study in men, gives doctors another tool to evaluate their patients and get a better sense of their heart disease risk. It also may lead to suggestions for lifestyle modifications to help patients lessen that risk.”
El Khoudary and her team evaluated clinical data, such as CT scans and blood pressure, on 524 women from Pittsburgh and Chicago enrolled in the Study of Women’s Health Across the Nation (SWAN). The women were in varying stages of menopause, averaged 51 years old and were not on hormone replacement therapy. After accounting for the potential health effects of lifestyle and socioeconomic factors, such as smoking, alcohol consumption and financial strain, the researchers determined that, not surprisingly, the more fat a woman carries overall, the higher her risk for a fatty heart. However, white women with higher body mass indexes, or BMI, which is a measure of overall body fat, had significantly more heart fat, as measured by a CT scan, than black women with the same BMI.
For black women, the levels of heart fat were greater if they carried more fat in their midsection, as measured by a cross-sectional CT scan, compared with white women with the same volume of fat in their midsection. The team found that the heart fat black women with larger waistlines accumulate is closer to their hearts than the fat the white women with higher BMIs accumulate. Fat close to the heart secretes inflammatory markers directly to the heart tissue and produces a greater detrimental effect as it expands. “We’ve now come to very similar conclusions that show excess abdominal fat is worse for both black men and women, and a higher BMI is worse for white men and women when it comes to their odds of having more fat around their hearts,” Khoudary said. “There is something going on here that warrants further investigation to determine why it is happening and what tailored interventions doctors may prescribe to help their patients lower their risk.”
Is Small Weight Gain Bad For The Heart?
Modest weight gains - even among those who aren’t overweight - can cause dangerous changes to the heart, but small amounts of weight loss can improve the condition, research from UT Southwestern Medical Center cardiologists shows. The report - published in the Journal of the American Heart Association - found that weight increases of as little as five percent can result in a remodeling of the heart. That’s the equivalent of a 6.5-pound gain for a 130-pound woman or about a 7.5-pound gain for a 150-pound man. “The take-home message is that weight gain is linked to abnormal changes in the heart muscle,” said cardiologist Dr. Ian Neeland, Assistant Professor of Internal Medicine at UT Southwestern and senior author of the study. “Regardless of the weight you start at, gaining weight damages the heart whereas losing weight improves the heart.”
Researchers reviewed MRI images of the heart before and after seven years and found that weight gain caused the heart to get bigger and thicker, with its thicker walls reducing the amount of space left to hold and pump out blood, which can lead to heart failure, Dr. Neeland said. “You get larger, thicker, smaller-cavity hearts that can’t fill very well with blood, and so the blood backs up to the lungs.”
Almost six million Americans suffer from heart failure, leaving the heart unable to pump enough blood to support the body. About half of those with the disease die within five years of diagnosis, according to the Centers for Disease Control and Prevention. The good news from the study is that even small amounts of weight loss can improve the condition of the heart, even for those who were not overweight. But the more important message is don’t gain. “The people who were not obese, when they started gaining weight, it was worse for them than gaining weight was for the people who were obese,” Neeland said. “Even if you can’t lose weight, focus on not gaining weight.”
Maintaining weight might be hard for many. American adults tend to gain progressively through middle age, according to the Agency for Healthcare Research and Quality. On average, they add 1.1 to 2.2 pounds per year and this amount can lead to obesity over time even for those who started at a normal weight. UTSW researchers looked at MRIs for 1,262 participants in the Dallas Heart Study, an ongoing multiethnic study of adults in Dallas County. Tests were taken between 2000 and 2002, and again between 2007 and 2008, then examined to determine the heart’s left ventricular mass and diastolic volume, mass-to-volume ratio, wall thickness, and ability to eject blood.
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