Genetic risk of developing obesity is driven by variants that affect the brain

Over the past decade, scientists have identified hundreds of different genetic variants that increase a person’s risk of developing obesity. But a lot of work remains to understand how these variants translate into obesity. Now scientists at the University of Copenhagen have identified populations of cells in the body that play a role in the development of the disease — and they are all in the brain.

“Our results provide evidence that biological processes outside the traditional organs investigated in obesity research, such as fat cells, play a key role in human obesity,” says Associate Professor Tune H Pers from the Novo Nordisk Foundation Center for Basic Metabolic Research (CBMR), at the University of Copenhagen, who published his team’s findings in the internationally-recognized journal eLife.

“We identified cell types in the brain that regulate memory, behavior and processing of sensory information that are involved in the development of the disease. Further investigation of these areas of the brain may tell us why some of us are more susceptible to develop obesity than others.”

A mosaic of brain cell populations contribute to obesity

The discovery was made by developing computational tools that combine two different sets of data. The first set is genome-wide association study data from around 450,000 people. This data compares a person’s health and physical attributes, such as their body weight, to their unique genome. Doing so reveals that people with obesity are much more likely to have a range of genetic variants in common.

The second set is single-cell RNA-sequencing data of more than 700 different types of mouse cell populations. Different cells express different parts of the genome, so this data set contains the unique genetic fingerprint for each cell population.

The team at CBMR integrated the two data sets and found that the genetic variants, which are strongly associated with obesity, are near genes expressed by 26 cell populations acting as different types of neurons.

Obesity is not a lack of willpower

We already know that the brain plays an important role in obesity by regulating how the body maintains its energy needs. It does so by processing signals from within the body about the energy stores and food intake, as well as external signals such as the sight and smell of food.

The new findings suggest that a person’s risk of developing obesity is driven by populations of cells that process sensory stimuli and direct actions related to feeding and behavior. They also identified specific brain cell types that support a role of learning and memory in obesity.

“The next step is to explore how defects in parts of the brain traditionally known to regulate memory and integration of sensory signals actually makes us more vulnerable to become obese,” says Tune H Pers.

“Our journey, to understand why some of us develop obesity, has only just begun. Our findings reinforce the growing body of evidence that obesity is far more complex than previously recognized and not can be reduced to a simple question about lack of willpower.”

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Association between screen time use, diet and other health factors

The era of the television brought with it the TV dinner — a fast, convenient meal that, while nutritionally questionable, meant the whole family could gather together on the sofa to enjoy “The Ed Sullivan Show” and eat their Swanson Salisbury steak, too.

Over the next several decades, advancements in technology and the ubiquity of streaming services has allowed for the proliferation of binge-watching culture, where hours spent sedentary rack up faster than “Jeopardy” points, and greasy fast food is only a few taps on your smartphone away.

Chris Wharton, assistant dean of innovation and strategic initiatives at Arizona State University’s College of Health Solutions, whose research interests include lifestylewide behavior change, wanted to know what kind of relationship the time we spend in front of screens has with various health behaviors and factors.

In a study recently published in BMC Public Health, one of the largest open access public health journals in the world, Wharton found that heavy users of screens — defined as those who use screens an average of 17.5 hours per day — reported the least healthful dietary patterns and the poorest health-related characteristics compared with moderate and light users, who averaged roughly 11.3 and 7 hours of screen use per day, respectively.

“A lot of screen time-related literature has primarily focused on television,” Wharton said. “But with the advancement of all these other types of devices that people use throughout the day, we wanted to see how health behaviors and factors are associated with a variety of screen-based devices.”

For the study, more than 900 adults across the U.S. who owned a television and at least one other device with a screen were asked to complete a survey to assess screen time use across multiple devices, dietary habits, sleep duration and quality, perceived stress, self-rated health, physical activity and body mass index.

Among the findings, unique dietary habits were associated with different types of screen use such that heavy users of TV and smartphones displayed the least healthful dietary patterns compared with heavy users of TV-connected devices, laptops and tablets.

Additionally, heavy users of smartphones reported the lowest quality of sleep.

“I find that important and interesting because it does back up what we understand about smartphones,” Wharton said. “We love to look at our phones and worry ourselves with the news right before we go to bed. But one of the simplest things people can do for their health when it comes to screens — which is probably one of the hardest things to do because of the convenience and their addictive nature — is putting all those devices down, in particular your smartphone, two hours before bedtime.”

Wharton also explored the phenomenon of binge-watching, defined as watching multiple episodes of a television program in a single sitting, and found that it was significantly associated with less healthy dietary patterns, including frequency of fast food consumption, eating family meals in front of a television and perceived stress.

“We’re engaging with media in lots of different ways, and in mobile ways,” Wharton said. “And across a lot of these devices, heavy users were engaging in a lot of fast food consumption. So the convenience of (screen use) seems to be associated with the convenience of fast food.”

That is, with the exception of laptops, which Wharton attributes to the likelihood that laptops are more often used for work than entertainment.

Wharton said the results of this study lay the foundation for future research into screen time interventions because they give researchers insight into which negative health effects are associated with which types of devices.

“When we look at interventions to help people eat more healthfully, as it relates to screen time, maybe we can’t just focus on television. The smartphone might be another really important factor in that,” he said. “Or if we want to improve physical activity, maybe we don’t need to think about smartphones but we do need think about TVs.”

In another study, currently pending publication, Wharton asked 10 participants to forgo screen use of any kind from the time they got home after work to the time they went to sleep for two weeks straight.

“We have some qualitative data to suggest that when people eliminate screens from their lives at night, magical things happen,” he said. “Initial results suggest that people have to figure out what to do with this time, so they’re doing things like spending more face-to-face with family and friends, cooking and preparing food, being physically active and engaging in hobbies. Things that are fulfilling in physically healthful ways and mentally healthful ways that you don’t get when the majority of your day is engaged with screens.”

Wharton himself has been making an effort to be especially conscious of his screen time use during the pandemic (he’s even taken up the violin), a time when many of us are hearing the opposite message.

“I worry when people say, ‘Now is the time to re-up your Netflix subscription. What else are you going to do?'” Wharton said. “I would flip that on its head and say, ‘Oh my gosh, now is the time to think about all the things to do other than sit in front of screens.’

“COVID is really bringing this into crystal-clear focus, that our lives are fully mediated by screens. They were before, they especially are now. I think it’s a good time to think about what a healthy but technologically plugged-in life could look like where screens aren’t the only way in which we interact and do everything in our life, but instead are just a small side component of everything else that we do. We are nowhere near a conclusion like that, but I think we need to get there because screens have come to dominate us, and they drive real problems in our health.”

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Low level alcohol use during pregnancy can impact child’s brain development

New research from the University of Sydney finds that even low levels of alcohol consumption during pregnancy can have an impact on a child’s brain development and is associated with greater psychological and behavioural problems in youth including anxiety, depression and poor attention.

Published today in the American Journal of Psychiatry, the study was led by the University’s Matilda Centre for Research in Mental Health and Substance Use.

The impact of low-level alcohol use during pregnancy on child development is relatively unknown and there has been extensive debate about whether there is a safe level of consumption.

The researchers investigated whether any alcohol consumption in pregnancy was related to psychological, behavioural, neural and cognitive differences in children aged nine to ten years. With a sample of 9,719 youth, this is the largest study to investigate the impacts of low-level alcohol use during pregnancy. Low levels of drinking were considered one to two drinks per occasion with maximum of six drinks per week.

“Our research found that even small amounts of alcohol consumed while pregnant can have a significant impact on a child’s brain development,” said lead author Ms Briana Lees, PhD candidate at the Matilda Centre.

“Previous research has shown that very heavy alcohol use, such as binge drinking, during pregnancy can cause harm to the baby. However, this study shows that any alcohol use during pregnancy, even low levels, is associated with subtle, yet significant behavioural and psychological effects in children including anxiety, depression and poor attention.

“This study is so important because in Australia, around 50 percent of women drink alcohol before they know they are pregnant, and 25 percent do so after they know. The vast majority consume one or two standard drinks per occasion which this study shows is enough to impact the baby’s brain.”

Study findings

In the study, 25 percent of children had been exposed to alcohol in utero (in the womb), 60 percent of these children had been exposed to low-level alcohol use, and 40 per cent had been exposed to heavier levels. Heavier exposure being three or more drinks per occasion or seven or more drinks per week.

Children who were exposed to low levels of alcohol in-utero at any time during pregnancy experienced more psychological/emotional problems (including anxiety, depression and being withdrawn) and behavioural problems (including poor attention and being impulsive) than unexposed children. There was a 25 percent increased likelihood of an attention deficit hyperactivity disorder (ADHD) diagnosis in children who were exposed to slightly heavier levels of alcohol (approximately 36 drinks) in the first 6-7 weeks of pregnancy. Heavier alcohol use during early pregnancy was also associated with rule breaking behaviour and aggression, with a 30 percent higher risk of the child being diagnosed with oppositional defiant disorder than unexposed youth.

There were differences observed in brain volume and surface area among the exposed children which contributed to the psychological and behavioural problems. The estimated number of drinks consumed during pregnancy ranged from 0-90 with the average being 27. The majority of drinks were consumed in the first 6-7 weeks prior to pregnancy knowledge.

“Generally, the more a child was exposed to alcohol in utero the more severe the outcomes were,” said Ms Lees.

“Children experienced negative effects even if they were only exposed to low levels of alcohol during very early pregnancy (approximately 16 drinks in the first six to seven weeks) and then the mother stopped drinking. The difficulty is many women don’t know they are pregnant at that early stage.

Senior author Professor Maree Teesson, Director of the Matilda Centre said these findings are important for families, clinicians and policy makers moving forward.

“This research highlights the importance for women to be aware of the effects that even low levels of drinking can have on the brain development of babies,” she said.

“The safest option during pregnancy is to abstain from drinking any alcohol.

“This information is also important for women planning pregnancies. Even when planning pregnancy, it is safer to abstain from any drinking. Any alcohol consumption from conception throughout the entire pregnancy can impact the brain development of their baby.”

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Materials provided by University of Sydney. Note: Content may be edited for style and length.

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Vitamin E needed for proper nervous system development

In research with key ramifications for women of childbearing age, findings by Oregon State University scientists show that embryos produced by vitamin E-deficient zebrafish have malformed brains and nervous systems.

“This is totally amazing — the brain is absolutely physically distorted by not having enough vitamin E,” said Maret Traber, a professor in the OSU College of Public Health and Human Sciences.

The study led by Traber, the Ava Helen Pauling Professor at Oregon State’s Linus Pauling Institute, was published today in Scientific Reports.

Zebrafish are a small freshwater species that go from a fertilized egg to a swimming fish in about five days. They are highly prized for studying the development and genetics of vertebrates.

Zebrafish share a remarkable similarity to humans at the molecular, genetic and cellular levels, meaning many findings are immediately relevant to humans. Embryonic zebrafish are of special interest because they develop quickly, are transparent and are easy to care for.

Vitamin E was discovered in 1922, identified because it was essential for fertilized rat eggs to culminate in live births.

“Why does an embryo need vitamin E? We’ve been chasing that for a long time,” said Traber, a leading authority on vitamin E who has been researching the micronutrient for three decades. “With this newest study we actually started taking pictures so we could visualize: Where is the brain? Where is the brain forming? How does vitamin E fit into this picture?”

In an embryo, a brain primordium and the neural tube appear early and will form the nervous system and “innervate” — supply with nerves — all organs and body structures. Without vitamin E, the zebrafish embryos showed neural tube defects and brain defects.

“They were kind of like folic acid-deficient neural tube defects, and now we have pictures to show the neural tube defects and brain defects and that vitamin E is right on the closing edges of the cells that are forming the brain,” Traber said.

In healthy organisms, neural crest cells drive the creation of facial bones and cartilage and innervate the body, building the peripheral nervous system.

“Acting as stem cells, the crest cells are important for the brain and spinal cord and also go on to be the cells of about 10 different organ systems including the heart and liver,” Traber said. “By having those cells get into trouble with vitamin E deficiency, basically the entire embryo formation is dysregulated. It is no wonder we see embryo death with vitamin E deficiency.”

Traber likens it to the children’s game KerPlunk, in which kids take turns pulling out the straws that support several dozen marbles in a vertical tube. When the wrong straw is pulled out, everything collapses; vitamin E is the straw whose extraction brings down the house on embryo development, especially with the brain and nervous system.

“Now we’re at the point where we’re so close being able to say exactly what’s wrong when there isn’t enough vitamin E but at the same time we’re very far away because we haven’t found what are the genes that are changing,” she said. “What we know is the vitamin E-deficient embryos lived to 24 hours and then started dying off. At six hours there was no difference, by 12 hours you see the differences but they weren’t killing the animals, and at 24 hours there were dramatic changes that were about to cause the tipping point of total catastrophe.”

Vitamin E, known scientifically as alpha-tocopherol, has many biologic roles and in human diets is most often provided by oils, such as olive oil. It is found in high levels in foods such as hazelnuts, sunflower seeds and avocados.

Vitamin E is a group of eight compounds — four tocopherols and four tocotrienols — distinguished by their chemical structure. Alpha-tocopherol is what vitamin E commonly refers to and is found in supplements and in foods associated with a European diet; gamma-tocopherol is the type of vitamin E most commonly found in a typical American diet.

“Plants make eight different forms of vitamin E, and you absorb them all, but the liver only puts alpha-tocopherol back into the bloodstream,” said Traber. “All of the other forms are metabolized and excreted. I’ve been concerned about women and pregnancy because of reports that women with low vitamin E in their plasma have increased risk of miscarriage.”

Joining Traber on the study were Brian Head of the Linus Pauling Institute, Jane La Du and Robyn Tanguay of the OSU College of Agricultural Sciences and Chrissa Kioussi of the OSU College of Pharmacy.

The Oregon Veterinary Diagnostic Lab supported the research with technical assistance, and the Ava Helen Pauling Endowment and the National Institute of Environmental Health Sciences of the National Institutes of Health contributed toward the study’s funding.

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Authoritative new analysis links increased omega-3 intake to cardioprotection and improved cardiovascular outcomes

A new study published in Mayo Clinic Proceedings provides the most comprehensive analysis of the role of omega-3 dosage on cardiovascular prevention to date. The meta-analysis, which is an in-depth review of 40 clinical trials, provides authoritative evidence for consuming more EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid) omega-3 fats.

The research concludes that EPA and DHA omega-3 intake is associated with reduced risk of coronary heart disease (CHD) events, the cause of 7.4 million deaths globally each year, and reduced risk of myocardial infarction (heart attack), including fatal heart attack.

Specifically, the study found that EPA+DHA supplementation is associated with a statistically significant reduced risk of:

  • Fatal myocardial infarction (35 percent)
  • Myocardial infarction (13 percent)
  • CHD events (10 percent)
  • CHD mortality (9 percent)

“The study supports the notion that EPA and DHA intake contributes to cardioprotection, and that whatever patients are getting through the diet, they likely need more,” said Carl “Chip” Lavie, MD, a cardiologist at Ochsner Health in New Orleans, LA, USA, and one of the study authors.

Cardiovascular benefits appear to increase with dosage. The researchers found that adding an extra 1000 mg of EPA and DHA per day decreased the risk of cardiovascular disease and heart attack even more: risk of cardiovascular disease events decreased by 5.8 percent and risk for heart attack decreased by 9.0 percent. The study looked at dosages of up to 5500 mg/day.

This research corroborates the results of an earlier meta-analysis from Harvard School of Public Health, published in fall 2019, that looked at EPA and DHA dosage using the 13 largest clinical studies. This new paper encompasses more than triple the number of studies, which represents the totality of the evidence to date and includes more than 135,000 study participants.

“When separate analyses arrive at similar results, that’s not only validating; it also underscores the science base needed to inform future intake recommendations,” said co-author Aldo Bernasconi, PhD, Vice President of Data Science for the Global Organization for EPA and DHA Omega-3s (GOED), Salt Lake City, UT, USA, which commissioned this study. “Because this paper included more studies and all dosages, the estimates for a dose-response are more precise and the conclusions stronger.”

EPA and DHA omega-3s are long-chain, marine-based fatty acids. Eating fish, particularly fatty fish such as salmon, anchovies and sardines, is the optimal way to get EPA and DHA omega-3s, since fish also provides other beneficial nutrients. However, most people around the world eat much less than the amount of fish recommended, so supplementing with omega-3s helps close the gap.

“People should consider the benefits of omega-3 supplements, at doses of 1000 to 2000 mg per day — far higher than what is typical, even among people who regularly eat fish,” added Dr. Lavie. “Given the safety and diminished potential for interaction with other medications, the positive results of this study strongly suggest omega-3 supplements are a relatively low-cost, high impact way to improve heart health with few associated risks and should be considered as part of a standard preventive treatment for most patients with cardiovascular diseases and those recovering from myocardial infarction.”

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Materials provided by Elsevier. Note: Content may be edited for style and length.

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