Warren symposium follows legacy of geneticist giant

If we want to understand how the brain creates memories, and how genetic disorders distort the brain’s machinery, then the fragile X gene is an ideal place to start. That’s why the Stephen T. Warren Memorial Symposium, taking place November 28-29 at Emory, will be a significant event for those interested in neuroscience and genetics. Stephen T. Warren, 1953-2021 Warren, the founding chair of Emory’s Department of Human Genetics, led an international team that discovered Read more

Mutations in V-ATPase proton pump implicated in epilepsy syndrome

Why and how disrupting V-ATPase function leads to epilepsy, researchers are just starting to figure Read more

Tracing the start of COVID-19 in GA

At a time when COVID-19 appears to be receding in much of Georgia, it’s worth revisiting the start of the pandemic in early 2020. Emory virologist Anne Piantadosi and colleagues have a paper in Viral Evolution on the earliest SARS-CoV-2 genetic sequences detected in Georgia. Analyzing relationships between those virus sequences and samples from other states and countries can give us an idea about where the first COVID-19 infections in Georgia came from. We can draw Read more

obesity

Intestinal bacteria modulate metabolism: link to obesity

The bacteria inside our guts are fine-tuning our metabolism, depending on our diet, and new research suggests how they accomplish it. Emory researchers have identified an obesity-promoting chemical produced by intestinal bacteria. The chemical, called delta-valerobetaine, suppresses the liver’s capacity to oxidize fatty acids.

The findings were recently published in Nature Metabolism.

“The discovery of delta-valerobetaine gives a potential angle on how to manipulate our gut bacteria or our diets for health benefits,” says co-senior author Andrew Neish, MD, professor of pathology and laboratory medicine at Emory University School of Medicine.

“We now have a molecular mechanism that provides a starting point to understand our microbiome as a link between our diet and our body composition,” says Dean Jones, PhD, professor of medicine at Emory University School of Medicine and co-senior author of the paper.

Gut bacteria produce delta-velerobetaine, which suppresses the liver’s capacity to oxidize fatty acids

The bacterial metabolite delta-valerobetaine was identified by comparing the livers of conventionally housed mice with those in germ-free mice, which are born in sterile conditions and sequestered in a special facility. Delta-valerobetaine was only present in conventionally housed mice.

In addition, the authors showed that people who are obese or have liver disease tend to have higher levels of delta-valerobetaine in their blood. People with BMI > 30 had levels that were about 40 percent higher. Delta-valerobetaine decreases the liver’s ability to burn fat during fasting periods. Over time, the enhanced fat accumulation may contribute to obesity.

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Burning fat like a baby

Newborn humans and hibernating mammals have high levels of brown adipose tissue, which they use to generate heat. Adult humans generally don’t have abundant brown adipose tissue, even if they have lots of “white” fat. Increasing brown fat’s activity may be an approach to treat obesity and related metabolic disorders.

Recently researchers identified an enzyme called Them1 (thioesterase superfamily member 1) as a factor that limits heat generation in brown adipose tissue. Emory biochemist Eric Ortlund and his lab showed how part of the Them1 enzyme binds a certain type of lipid molecule, and also how that part of the enzyme anchors the enzyme close to lipid droplets in adipose cells. Former graduate student Matt Tillman, now a postdoc at Duke, was the first author of the new paper in Proceedings of the National Academy of Sciences.

“In this study, we show Them1 contains a lipid sensor module that detects specific lipids within the cell to regulate its activity,” says Tillman.

In brown adipose cells, the lipid-sensing domain of Them1 is needed for localization around lipid droplets

From Tillman et al PNAS (2020)

He and his colleagues showed that a lipid known for its role in cell signaling, lysophosphatidylcholine or LPC, inhibits Them1 activity, which in turn activates thermogenesis in brown adipose tissue. In contrast, other fatty acids that serve as fuel tend to activate Them1. This regulatory system within Them1 allows the cell to sense its metabolic state and decide when to burn or conserve fat.

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Food deserts and cardiovascular risk

Heval Mohamed Kelli, MD got some attention at the American College of Cardiology meeting over the weekend with his work on food deserts — low-income areas distant from access to healthy food.

As Medscape summarized the results: “Atlantans living in disadvantaged areas where the nearest supermarket was a mile or more away were more likely to have hypertension or hyperlipidemia, smoke, be obese, and have higher levels of systemic inflammatory markers and stiffer arteries.”

Kelli_cover

Kelli at Clarkston Health Clinic, which Emory doctors helped establish in 2015. Clarkston is considered a “food desert”.

For more on Kelli’s journey from Syrian refugee to Clarkston, GA teenager to Emory cardiology researcher, check out this feature in Emory Magazine.

His research was conducted through the Emory Clinical Cardiovascular Research Institute, using information on 712 community participants from the META-Health study and 709 Emory/Georgia Tech employees from the Predictive Health study.

Three possibilities for further investigation:

*Income, education, race and geography are intertwined. “Whether lack of access to healthy foods, low income, or low education is driving these processes needs to be further studied,” Kelli and colleagues concluded.

*For detailed maps of food deserts, not just in Atlanta and/or determined using different criteria, the U.S. Department of Agriculture makes it possible.

*This Atlantic article makes the point that “when it comes to nutrition access, the focus should be on poverty, not grocery-store location.” You can lead people to the supermarket (or build one close to where they live), but you can’t make them eat a Mediterranean diet. Studies from Los Angeles showed that obesity increased more in some neighborhoods, even despite a ban on new fast food restaurants.

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The unsweetened option

Pediatric hepatologist Miriam Vos is starting a new study testing the effects of a low-sugar diet in children with NAFLD (non-alcoholic fatty liver disease). The study is supported by the Nutrition Science Initiative and conducted in a partnership with UCSD/Rady Children’s Hospital, San Diego. See below for more on NUSI.

While there are no medications approved for NAFLD – a healthy diet and exercise are the standard of care – plenty of drugs are under development, as a recent article from Mitch Leslie in Science illustrates. As a reality check and benchmark, the NUSI study will address whether the low-tech intervention of altering diet can be effective.

Lab Land has delved into NAFLD and its increasing prevalence in previous posts. Plenty of correlational data shows that sugar intake is linked to NAFLD (a recent paper from the Framingham Heart Study), but Vos points out that there are no studies showing that reducing sugar is sufficient to drive improvement in the disease.

Diet is a challenge to examine in humans rigorously. In observational studies, investigators are always bumping up against the limits of memory and accurate reporting. In an interventional study with adults, it’s possible to provide them a completely defined menu for a short time in a closed environment, but that’s less practical for longer periods or with children.

The press release announcing the NUSI study says: half of the families will eat and drink what they normally do while the rest will be put on sugar-free meals and snacks, all of which will be provided for the participants and their families for eight weeks.

Miriam Vos, MD

I was curious about how this would work, especially for boys aged 11 to 16 (the participants in her study), so I asked Vos more about it for Lab Land.

“We try to provide them a diet that is otherwise similar to what the family is used to,” she says. “For example, if they’re accustomed to home-cooked meals, our team of nutritionists will work with them to find different recipes.” Read more

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Are TrkB agonists ready for translation into the clinic?

Our recent news item on Emory pathologist Keqiang Ye’s obesity-related research (Molecule from trees helps female mice only resist weight gain) understates how many disease models the proto-drug he and his colleagues have discovered, 7,8-dihydroxyflavone, can be beneficial in. We do mention that Ye’s partners in Australia and Shanghai are applying to begin phase I clinical trials with a close relative of 7,8-dihydroxyflavone in neurodegenerative diseases.

Ye’s 2010 PNAS paper covered models of Parkinson’s, stroke and seizure. Later publications take on animal models of depression, Alzheimer’s, fear learning, hearing loss and peripheral nerve injury. Although those findings begin to sound too good to be true, outside laboratories have been confirming the results (not 100 percent positive, but nothing’s perfect).  Plenty of drugs don’t make it from animal models into the clinic, but this is a solid body of work so far.

 

 

 

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Unexpected mechanism for a longevity lipid

The idea that particular lipid components, such as omega-3 fatty acids, promote health is quite familiar, so the finding that the lipid oleoylethanolamide or OEA extends longevity in the worm C. elegans is perhaps not so surprising. However, a recent paper in Science is remarkable for what it reveals about how OEA exerts its effects.

Scientists at Baylor College of Medicine led by Meng Wang, with some help from biochemists Eric Ortlund and Eric Armstrong at Emory, discovered that OEA is a way one part of the cell, the lysosome, talks to another part, the nucleus. Lysosomes are sort of recycling centers/trash digesters (important for autophagy) and the nucleus is the control tower for the cell. The authors show that starting in lysosomes, OEA travels to the nucleus and activates nuclear hormone receptors (the Ortlund lab’s specialty). Read more

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Gene duplication leads to obesity in childhood syndrome

A team of researchers has discovered a genetic syndrome that causes childhood obesity, intellectual disability and seizures. The syndrome comes from an “unbalanced” chromosomal translocation: affected individuals have additional copies of genes from one chromosome and fewer copies of genes from another.

The results were published this week in Proceedings of the National Academy of Sciences, Early Edition.

Katie Rudd, PhD, assistant professor of human http://www.raybanoutletes.com/ genetics at Emory University School of Medicine, is senior author of the paper. Research specialist Ian Goldlust, now a graduate student in the NIH-Oxford-Cambridge Scholars Program, is the first author. Co-authors include investigators from around the USA and Australia.

Rudd’s team was able to connect the contribution of one gene, GNB3, among many involved in the translocation, to the obesity aspect of the syndrome. Her lab created a mouse model with an extra copy of the GNB3 gene and found that the mice are obese. The mice are on average 6 percent (males) or 10 percent (females) heavier.

Rudd says her work was greatly assisted by collaboration with the Unique Rare Chromosome Disorder Support Group, a UK-based charity. Within Unique, a few parents had together found that their children had translocations involving the same chromosomes and similar symptoms. They contacted Rudd and helped her find additional affected families. Her study includes seven unrelated patients.

“It really was a group effort, and Unique was the linchpin,” she says. “Managing to find seven families with exactly the same rare translocation would have been extremely difficult otherwise.”

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Americans cutting sugar – but it’s still not enough

In America’s battle against obesity, there is some good news. According to a study conducted by Emory researchers, Americans consumed nearly a quarter less added sugars in 2008 than they did 10 years earlier.

The study, published in the American Journal of Clinical Nutrition in July 2011, found that the consumption of added sugars, such as those found in sodas, sports drinks, juices and sweetened dairy products, decreased among all age groups over a decade. The largest decrease came in the consumption of sodas, traditionally the largest contributor to added sugar consumption, according to Jean Welsh, MPH, PhD, RN, study author and post-doctoral fellow in pediatric nutrition at Emory University School of Medicine.

“While we were hopeful this would be the case, we were surprised when our research showed such a substantial reduction in the amount of added sugar Americans are consuming,” said Welsh. “We’re hopeful this trend will continue.”

So, why the change? One of Welsh’s partners in the study, Miriam Vos, MD, MSPH, an assistant professor of pediatrics in the Emory University School of Medicine, and a physician on staff at Children’s Healthcare of Atlanta, attributes much of the shift to public education.

“Over the past decade, there has been a lot of public health awareness about obesity and nutrition, and I think people are starting to get the message about sugar,” says Vos. “We’re not trying to send a message that sugar is inherently bad. It’s more that the large amounts of sugar we consume are having negative effects on our health, including increasing our risk of obesity, diabetes and cardiovascular disease.”

The study interpreted data of 40,000 people’s diets collected by the Centers for Disease Control and Prevention (CDC) over 10 years.  From the surveys, researchers were able to calculate how much added sugar – that is sugar that is not originally part of a food – that Americans are consuming. In 1999-2000, the typical person’s daily diet included approximately 100 grams of added sugar, a number that had dropped to 77 grams by 2007 and 2008.

While the study shows that the amount of added sugar Americans are consuming is lower, it doesn’t mean the amount is low enough.

“The American Heart Association recommends that we get about five percent of our calories from added sugars,” says Vos. “In 1999 to 2000, people were consuming about 18 percent of their calories from added sugars. Over 10 years, that amount decreased to 14.5 percent of our daily calories, which is much better. But, clearly, 14.5 percent is still three times more than what is considered a healthy amount. We’re on the right track, but we still have room for improvement.”

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Emory experts weigh in on obesity at AACC Annual Meeting

The obesity epidemic took center stage at this year’s American Association of Clinical Chemistry (AACC) Annual Meeting. Several Emory experts took the podium to further explore obesity not only as a public health problem, but also as an issue that is changing the way we diagnose diseases and treat health issues in children.

Jeffrey Koplan, MD, MPH

Jeffrey Koplan, MD, MPH, director of the Emory Global Health Institute, led one of the meeting’s plenary sessions, emphasizing that obesity must be fought with changes in both public policy and personal decision-making. Koplan also noted that strategies to address obesity must be localized to fit each community because eating and exercise habits are often culturally specific.

Rising rates of obesity also are changing the way physicians and researchers define and diagnose certain diseases, including metabolic syndrome, a cluster of risk factors including insulin resistance, high blood pressure, cholesterol abnormalities and an increased risk for clotting. The common thread among patients with metabolic syndrome is that they are often overweight or obese.

Ross Molinaro, PhD

Pathologist Ross Molinaro, PhD, medical director of the Core Laboratory at Emory University Hospital Midtown and co-director of the Emory Clinical Translational Research Laboratory, presented insights into the important role of lab testing in the definition and diagnosis of metabolic syndrome.  In addition to new markers, Molinaro addressed the global prevalence of metabolic syndrome and the evolving criteria for diagnosis.

Miriam Vos, MD, MSPH

Responding to their members’ demand for more information on how obesity affects children, the AACC hosted a full-day symposium on pediatric obesity and related health complications such as diabetes and high blood pressure.  Miriam Vos, MD, MSPH, assistant professor of pediatrics in  Emory School of Medicine and a physician at Children’s Healthcare of Atlanta described non-alcoholic fatty liver disease as an increasingly common complication of childhood obesity that can cause inflammation and scarring of the liver.

Stephanie Walsh, MD

Stephanie Walsh, MD, assistant professor of pediatrics in Emory School of Medicine and medical director of child wellness at Children’s Healthcare of Atlanta, leads Children’s efforts in preventing and treating childhood obesity in Georgia, which currently has the second highest rate of childhood obesity in the country. Walsh addressed the effect of Children’s wellness initiative, called Strong4Life, on childhood obesity prevention in Georgia.

“From those in the lab, to those in clinic, to those who strategize and implement public health campaigns, we’re all going to need to work together to protect our children’s future,” says Walsh.

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Emory Cardiologist Weighs in on U.S. News Diet Ranking

 

Laurence Sperling, MD

U.S. News & World Report recently announced the results of its first-ever Best Diets rankings evaluating some of the country’s most popular diets.

Emory Heart & Vascular Center cardiologist Laurence Sperling served on a panel of 22 health experts selected by U.S. News to help develop the rankings. Sperling is the medical director of the Emory Heartwise Risk Reduction Program and professor of medicine at Emory University School of Medicine.

Sperling and his panel colleagues reviewed information about 20 well-known diets, from Atkins to Zone, and rated each one on specific measures such as safety, easiness to follow and nutritional completeness.

Using the experts’ ratings, U.S. News developed five diet categories to address a broad range of consumers’ dieting goals and needs including Best Diabetes Diets, Best Heart Diets, Best Weight Loss Diets and Best Overall. “The goal of the Best Diets rankings is to help consumers find authoritative guidance on healthful diets that will work for them over the long haul,” said Lindsay Lyon, U.S. News‘s Health News Editor.

Weight Watchers ranked first in the Weight Loss category. Tied for number two were Jenny Craig and the Raw Food Diet, an approach that challenges dieters to avoid foods that have been cooked.

The government-endorsed DASH Diet took the top spot as the best diet overall. Three diets tied at number two, excelling in all measures U.S News considered: the Mediterranean Diet, the TLC Diet, and Weight Watchers.

For a complete list of the new diet rankings, please visit:

http://health.usnews.com/best-diet

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