Obesity

Posted on Diabetes, Obesity, Weight Loss

Time-restricted eating reshapes gene expression throughout the body.

Science image


Time-restricted eating reshapes gene expression throughout the body. In this illustration, the Ferris wheel displays the interconnected organ systems working smoothly during time-restricted eating, represented by the clock in the middle CREDIT Salk Institute

Numerous studies have shown the health benefits of time-restricted eating, including an increase in life span in laboratory studies, and practices like intermittent fasting, a hot topic in the wellness industry. However, how it affects the body on the molecular level and how those changes interact across multiple organ systems has not been well understood. Now, Salk scientists show in mice how time-restricted eating influences gene expression across more than 22 regions of the body and brain. Gene expression is the process through which genes are activated and responds to their environment by creating proteins.

The findings, published in Cell Metabolism on January 3, 2023, have implications for many health conditions where time-restricted eating has shown potential benefits, including diabetes, heart disease, hypertension, and cancer.

“We found that there is a system-wide, molecular impact of time-restricted eating in mice,” says Professor Satchidananda Panda, senior author and holder of the Rita and Richard Atkinson Chair at Salk. “Our results open the door for looking more closely at how this nutritional intervention activates genes involved in specific diseases, such as cancer.”

For the study, two groups of mice were fed the same high-calorie diet. One group was given free access to food. The other group was restricted to eating within a feeding window of nine hours each day. After seven weeks, tissue samples were collected from 22 organ groups and the brain at different times of the day or night and analyzed for genetic changes. Samples included tissues from the liver, stomach, lungs, heart, adrenal gland, hypothalamus, different parts of the kidney and intestine, and different areas of the brain.

The authors found that 70 per cent of mouse genes respond to time-restricted eating.

“By changing the timing of food, we were able to change the gene expression not just in the gut or in the liver, but also in thousands of genes in the brain,” says Panda. 

Nearly 40 per cent of genes in the adrenal gland, hypothalamus, and pancreas were affected by time-restricted eating. These organs are essential for hormonal regulation. Hormones coordinate functions in different body and brain parts, and hormonal imbalance is implicated in many diseases, from diabetes to stress disorders. The results offer guidance on how time-restricted eating may help manage these diseases.

Interestingly, not all sections of the digestive tract were affected equally. While genes involved in the upper two portions of the small intestine—the duodenum and jejunum—were activated by time-restricted eating, the ileum, at the lower end of the small intestine, was not. This finding could open a new line of research to study how jobs with shiftwork, which disrupt our 24-hour biological clock (called the circadian rhythm) impact digestive diseases and cancers. Previous research by Panda’s team showed that time-restricted eating improved the health of firefighters, who are typically shifting workers.

The researchers also found that time-restricted eating aligned the circadian rhythms of multiple body organs.

“Circadian rhythms are everywhere in every cell,” says Panda. “We found that time-restricted eating synchronized the circadian rhythms to have two major waves: one during fasting and another just after eating. We suspect this allows the body to coordinate different processes.”

Next, Panda’s team will take a closer look at the effects of time-restricted eating on specific conditions or systems implicated in the study, such as atherosclerosis, which is a hardening of the arteries that is often a precursor to heart disease and stroke, as well as chronic kidney disease.

Posted on Obesity

Some guts are better than others at harvesting energy

Associate professor Henrik Roager


Associate professor Henrik Roager in the lab. CREDIT University of Copenhagen.

New research from the University of Copenhagen suggests that a portion of the Danish population has a composition of gut microbes that, on average, extracts more energy from food than do the microbes in the guts of their fellow Danes. The research is a step towards understanding why some people gain more weight than others, even when they eat the same.

Unfair as it, some of us seem to put on weight just by looking at a plate of Christmas cookies, while others can munch away with abandon and not gain a gram. Part of the explanation could be related to the composition of our gut microbes. This, according to new research conducted at the University of Copenhagen’s Department of Nutrition, Exercise and Sports.

Researchers studied the residual energy in the faeces of 85 Danes to estimate how effective their gut microbes are at extracting energy from food. At the same time, they mapped the composition of gut microbes for each participant.

The results show that roughly 40 percent of the participants belong to a group that, on average, extracts more energy from food compared to the other 60 percent. The researchers also observed that those who extracted the most energy from food also weighed 10 percent more on average, amounting to an extra nine kilograms.

“We may have found a key to understanding why some people gain more weight than others, even when they don’t eat more or any differently. But this needs to be investigated further,” says Associate Professor Henrik Roager of the University of Copenhagen’s Department of Nutrition, Exercise and Sports.

May increase the risk of obesity

The results indicate that being overweight might not just be related to how healthily one eats or the amount of exercise one gets. It may also have something to do with the composition of a person’s gut microbes. 

Participants were divided into three groups, based on the composition of their gut microbes. The so-called B-type composition (dominated by Bacteroides bacteria) is more effective at extracting nutrients from food and was observed in 40 percent of the participants.

Following the study, the researchers suspect that a portion of the population may be disadvantaged by having gut bacteria that are a bit too effective at extracting energy. This effectiveness may result in more calories being available for the human host from the same amount of food.

“The fact that our gut bacteria are great at extracting energy from food is basically a good thing, as the bacteria’s metabolism of food provides extra energy in the form of, for example, short-chain fatty acids , which are molecules that our body can use as energy-supplying fuel. But if we consume more than we burn, the extra energy provided by the intestinal bacteria may increase the risk of obesity over time,” says Henrik Roager.

Short travel time in the gut surprises

From mouth to esophagus, stomach, duodenum and small intestine, large intestine and finally to rectum, the food we eat takes a 12-to-36-hour journey, passing several stations along the way, before the body has extracted all the food’s nutrients.

The researchers also studied the length of this journey for each participant, all of whom had similar dietary patterns. Here, the researchers hypothesized that those with long digestive travel times would be the ones who harvested the most nutrition from their food. But the study found the exact opposite.

“We thought that there would be a long digestive travel time would allow more energy to be extracted. But here, we see that participants with the B-type gut bacteria that extract the most energy, also have the fastest passage through the gastrointestinal system, which has given us something to think about,” says Henrik Roager.

Confirms previous study in mice

The new study in humans confirms earlier studies in mice. In these studies, it was found that germ-free mice that received gut microbes from obese donors gained more weight compared to mice that received gut microbes from lean donors, despite being fed the same diet.

Even then, the researchers proposed that the differences in weight gain could be attributable to the fact that the gut bacteria from obese people were more efficient at extracting energy from food. This is the theory now being confirmed in the new study by the Department of Nutrition, Exercise and Sports.

“It is very interesting that the group of people who have less energy left in their stool also weigh more on average. However, this study doesn’t provide proof that the two factors are directly related. We hope to explore this more in the future,” says Henrik Roager. 

About gut bacteria:

  • Everyone has a unique composition of gut bacteria – shaped by genetics, environment, lifestyle and diet.
  • The collection of gut bacteria, called the gut microbiota, is like an entire galaxy in our gut, with a staggering 100 billion of them per gram of stool.
  • Gut bacteria in the colon serve to break down food parts that our body’s digestive enzymes can’t, e.g., dietary fibre.
  • Humans can be divided into three groups based on the presence and abundance of three main groups of bacteria that most of us have: B-type (Bacteroides), R-type (Ruminococcaceae) and P-type (Prevotella).
Posted on Diabetes, Obesity

Why late-night eating leads to weight gain, diabetes

People who are ‘night owls’ could have greater risk of type 2 diabetes and heart disease than those who are ‘early birds’
People who are ‘night owls’ could have greater risk of type 2 diabetes and heart disease than those who are ‘early birds’


Northwestern Medicine scientists have uncovered the mechanism behind why eating late at night is linked to weight gain and diabetes.

The connection between eating time, sleep and obesity is well-known but poorly understood, with research showing that overnutrition can disrupt circadian rhythms and change fat tissue.

New Northwestern research has shown for the first time that energy release may be the molecular mechanism through which our 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.

The paper, “Time-restricted feeding mitigates obesity through adipocyte thermogenesis,” will be published online today, and in print tomorrow (Oct. 21) in the journal Science.

“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, the Charles F. Kettering Professor of Medicine at Northwestern University Feinberg School of Medicine. He also is a Northwestern Medicine endocrinologist.

“When animals consume Western style cafeteria diets — high fat, high carb — the clock gets scrambled,” 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.”

Bass is also director of the Center for Diabetes and Metabolism and the chief of endocrinology in the department of medicine at Feinberg. Chelsea Hepler, a postdoctoral fellow in the Bass Lab, was the first author and did many of the biochemistry and genetics experiments that grounded the team’s hypothesis. Rana Gupta, now at Duke University, was also a key collaborator.

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,” Hepler said. “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 — or heat release through fat cells — prevented weight gain and improved health.

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 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 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, 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?

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.”

Posted on Exercise, Obesity

Exercise and obesity have the opposite impact on muscle, fat tissues; researchers demonstrate

New insight into how excess belly fat may increase cancer risk

 Exercise training is a well-known means of maintaining and restoring good health; however, the molecular mechanisms underlying the benefits of exercise are not yet completely understood. A new paper by researchers at Joslin Diabetes Center in Cell Metabolismsheds light on the complex physiological response to exercise.

Taking advantage of recent single-cell technologies and advancements in computational biology, a team led by Laurie J. Goodyear, PhD, senior investigator of Integrative Physiology and Metabolism at Joslin Diabetes Center, launched a collaboration with a computational biology and artificial intelligence lab at Massachusetts Institute of Technology led by Manolis Kellis, PhD, to investigate how three metabolic tissues respond to exercise and to high-fat diet-induced obesity at single-cell resolution. These first-of-their-kind results provide a reference atlas of the single-cell changes induced by the exercise and obesity in two different types of fat and muscle. The investigators determined that there are opposite responses to exercise and obesity across all three tissues and highlight prominent molecular pathways modulated by exercise and obesity.

“Regular physical exercise is a well-established intervention for prevention and treatment of obesity and diabetes, and our goal is to set the foundation for understanding the molecular changes and cell types mediating the systemic effects of exercise and obesity in different tissues throughout the body,” said Goodyear, also a professor of medicine at Harvard Medical School. “The results of this study are going to serve as a tremendous resource that can lead to so much other work – not just from our laboratory but from other labs, too – that could eventually lead to the discovery of novel therapeutic options for obesity and other chronic metabolic diseases.”

Goodyear and colleagues focused the current investigation on two kinds of white adipose tissue – or fat – and skeletal muscle taken from mice which were either trained or sedentary, and fed either a healthful chow diet or fed a high-fat diet (HFD) intended to mimic the typical Western diet. This effectively provided four groups of mice; chow-fed/sedentary, chow-fed/active, HFD/sedentary and HFD/active. Diet treatments were for six weeks, and exercise training was done by housing mice with free access to a running wheel for three weeks.

After three weeks of the exercise intervention, the animals’ tissues were analyzed with single-cell RNA sequencing, providing the researchers with a plethora of new data. Among the most striking findings, the scientists observed that genes governing extracellular modelling (ECM) and circadian rhythm were regulated by both exercise and obesity across all three tissue types. Obesity up-regulated ECM-related pathways, while exercise down-regulated them. Conversely, exercise up-regulated circadian-related pathways, and obesity down-regulated them.

“With respect to the circadian rhythm, we saw very quiet cells that weren’t metabolically active with the high-fat diet group,” said co-first author Pasquale Nigro, PhD, a senior member of the Goodyear lab at Joslin and an instructor in medicine at Harvard Medical School. “We discovered that exercise reversed this. It seemed that, when the circadian system is upregulated, cells become re-activated.”

“As one of the most effective strategies to maintain a healthy body and mind, exercise is increasingly understood to induce tissue-specific and shared adaptations in the context of many other diseases beyond obesity,” said co-first author Maria Vamvini, MD, staff physician at Joslin and instructor in medicine at Harvard Medical School. “By combining our knowledge as physiologists with the computational biology skills of the Kellis lab at MIT, we’ve been able to develop a single-cell atlas with more than 200,000 cells and 53 annotated cell types. This resource has the potential to help our research team as well as others reveal fundamental exercise-induced changes in a diverse set of diseases and physiological contexts such as cancer and aging.  This teamwork stands out as a model for what we can accomplish through collaboration.”

Posted on ADHD, Diabetes, Obesity

Pregnant women with obesity and diabetes may be more likely to have a child with ADHD

New knowledge about the link between infection during pregnancy and autism
New knowledge about the link between infection during pregnancy and autism

Children of women with gestational diabetes and obesity may be twice as likely to develop attention-deficit/hyperactivity disorder (ADHD) compared to those whose mothers did not have obesity, according to new research published in the Endocrine Society’s Journal of Clinical Endocrinology & Metabolism.

The estimated number of children aged 3–17 years ever diagnosed with ADHD is 6 million, according to data from 2016-2019. A major risk factor for ADHD in children is maternal obesity. Roughly 30% of women have obesity at their first doctor’s visit during pregnancy, and this number increases to 47% in women with gestational diabetes. Excessive weight gain during pregnancy in this population is a risk factor for children developing ADHD.

“Our study found pregnant women with obesity and gestational diabetes had children with long-term mental health disorders such as ADHD,” said Verónica Perea, M.D., Ph.D., of the Hospital Universitari MutuaTerrassa in Barcelona, Spain. “We did not find this association when these women gained a healthy amount of weight during pregnancy.”

The researchers studied 1,036 children born to women with gestational diabetes. Thirteen percent of these children were diagnosed with ADHD. The researchers found children of women with gestational diabetes and obesity were twice as likely to have ADHD compared to those born to mothers without obesity.

The researchers only found this association in women with gestational diabetes, obesity and excessive weight gain during pregnancy. The researchers did not observe a higher risk of ADHD in children of women with gestational diabetes and obesity if the amount of weight these women gained during pregnancy was within the normal range.

“It’s important for clinicians to counsel their patients on the importance of healthy weight gain during pregnancy,” Perea said.