Stories about: obesity

News note: GIANT study homes in on obesity genes

obesity genes
Illustration: Elena Hartley

Yes, some obesity is due to genetics. The largest and most powerful study to date has pinned down 14 variants in 13 genes that carry variations associated with body mass index. They provide new clues as to why some people tend to gain weight and have more trouble losing it. Eight of the variants were in genes not previously tied to human obesity.

The study, published last month, was conducted by the Genetic Investigation of Anthropometric Traits (GIANT) consortium, an international collaboration involving more than 250 research institutions — the same group that brought us height-related genes last year. It combined genetic data from more than 700,000 people and 125 different studies to find rare or low-frequency genetic variants that tracked with obesity.

The study focused on rarer variants in the coding portions of genes, which helped pinpoint causal genes and also helped discover variants with larger effects that those previously discovered by the GIANT consortium. For example, carriers of a variant in the gene MC4R (which produces a protein that tells the brain to stop eating and to burn more energy) weigh 15 pounds more, on average, than people without the variant.

Computational analysis provided some interesting insights into what the 13 genes do. Some, for example, play a role in brain pathways that affect food intake, hunger and satiety. Other variants affect fat-cell biology and how cells expend energy.

This study provided an important confirmation of the role of the nervous system in body weight regulation,” says Joel Hirschhorn MD, PhD, a pediatric endocrinologist and researcher at Boston Children’s Hospital and the Broad Institute of MIT and Harvard, who co-led the study with Ruth Loos, PhD, of the Icahn School of Medicine at Mount Sinai. “Many of the genes from this study were not known to be associated with obesity, but our computational analysis independently implicates these new genes in strikingly similar neuronal pathways as the genes that emerged from our previous work. In addition, our approach newly highlighted a role for genes known to be important in ‘brown fat,’ a type of fat that burns energy and may help keep people lean.”

The researchers think the new findings could help focus the search for new therapeutic targets in obesity.  Read more in Nature Genetics and this press release from Mount Sinai.

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News Note: More evidence that high-glycemic diets cause obesity

a high-glycemic diet

A large genetic analysis lends credence to the idea that insulin spikes after eating high-glycemic foods promote weight gain. People genetically predisposed to produce higher than normal levels of insulin after eating processed carbohydrates — “bad carbs” like white bread, potatoes and refined sugar — were more likely to be obese, the study found.

The researchers, led by David Ludwig, MD, PhD, of Boston Children’s Hospital, Joel Hirschhorn, MD, PhD, of Boston Children’s and the Broad Institute, and Jose Florez, MD, PhD, of the Broad Institute and Massachusetts General Hospital, tapped a collection of large-scale genome-wide association studies. Analyzing data from more than 26,000 people who had glucose challenges, they identified genetic variants linked with high insulin levels 30 minutes after the challenge.

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DNA methylation patterns linked to obesity and its complications

DNA methylation obesity
(Methylated DNA: Christoph Bock, Max Planck Institute for Informatics/Wikimedia Commons)

Why do some people seem to be prone to weight gain? Obesity has been linked to a variety of genetic changes, yet these differences don’t fully explain the variation in people’s body mass index (BMI). “Even though we’ve genetically sequenced more and more people at greater and greater breadth and depth, we haven’t completely explained who develops obesity and why,” says Michael Mendelson, MD, ScM, a pediatric cardiologist with Boston Children’s Hospital’s Preventive Cardiology Program.

Nor do prior studies explain why some overweight people develop health complications from obesity, like cholesterol problems, diabetes, hypertension and heart disease, while others don’t. Now comes strong evidence that an important factor is DNA methylation — a so-called epigenetic modification that influences whether genes are turned on or off.

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Gene for salivary enzyme found unrelated to obesity

(Jaimie Duplass:Shutterstock)
child eating cracker-cropped-shutterstock_169956-Jaimie Duplass

Sometimes it’s just as important to rule a gene out as the cause of a condition as it is to rule it in, especially for complex, multi-gene traits like obesity. In a report published yesterday by Nature Genetics, a gene once thought to be the single greatest genetic influence on human obesity actually has nothing to do with body weight.

The study, led by researchers at Harvard Medical School (HMS) and Boston Children’s Hospital, also provides the first effective ways to analyze complicated parts of the genome.

The gene in question, AMY1, encodes an enzyme in our saliva that helps convert starch into sugar. “There’s been some speculation that because this enzyme helps get nutrients out of our food, it could be linked to obesity,” said Christina Usher, a graduate student at HMS and first author on the paper.

What’s complicated is that people can have anywhere from 2 to 14 copies of AMY1—or more. In 2014, an unrelated international group reported in Nature Genetics that people with fewer than four copies of AMY1 had a roughly eight times greater risk for obesity than people with more than nine copies of the gene. AMY1 therefore appeared to be protective.

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At this pediatric ‘shark tank,’ the children win

Part of a continuing series of videotaped sessions at Boston Children’s Hospital’s recent Global Pediatric Innovation Summit + Awards 2014.

It was an ABC “Shark Tank” lover’s dream: At this pediatric Innovation Tank moderated by Daymond John, venture capitalists and clinicians fielded pitches from innovators looking to advance their care solution before a packed audience. The contenders:

  • A soft sleeve and wrap to keep catheter central lines in place, created by a parent
  • A handheld device that cleanses central line hubs, freeing up clinicians’ time
  • A mobile weight-loss program for kids and teenagers, designed to teach healthy habits

We won’t disclose the results–you’ll just have to watch the proceedings–but as emcee Bruce Zetter, PhD, of Boston Children’s put it, “The children win.”

Stay tuned as we post more sessions from the Pediatric Innovation Summit (also available on YouTube) and read our blog coverage.

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What can pulse pressure teach us about pediatric obesity?

pulse pressure
Subtract 68 from 100 to get a pulse pressure of 42 (Wikiphoto/Creative Commons)

Second in a two-part series on cardiovascular prevention in children. Read part 1.

Carrying too much weight is tough on the body. The dramatic rise of obesity in recent years means more and more people are confronting increased cardiovascular risk due to changes in their blood vessels, cholesterol levels, blood pressure, and blood sugar. And the problem isn’t limited to adults: Today, there are more than three times as many obese children in the U.S. than there were in the early 1970s.

However, not every person with excess weight has cardiac risk factors, and not everyone with cardiac risk factors carries excess weight. So what is the relationship between childhood obesity and cardiac risk factors later in life? What links excess weight to its consequences?

Justin Zachariah, MD, MPH, a cardiologist at Boston Children’s Hospital, was inspired to investigate these “risk factors of risk factors” when he observed a pattern in his pediatric preventive cardiology clinic. He noticed that many of his patients who were carrying excess weight did not have very high blood pressure, or hypertension.

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Q+A: The economic case for obesity treatment

medical costsCan putting a price tag on childhood obesity propel treatment and prevention efforts into comprehensive action? Perhaps, says David Ludwig, MD, PhD, of Boston Children’s Hospital.

Although the U.S. Task Force on Childhood Obesity set a goal of dropping obesity prevalence among youth to 5 percent by 2030, efforts have failed to make a significant dent. Recent data indicate only slight dips in obesity prevalence among 6- to 19-year-olds in some states. And other data show that the prevalence of extreme obesity in children continues to rise.

With nearly 20 percent of U.S. children tipping the scales as obese, policymakers need not only to act but also to justify the investment in childhood obesity treatment and prevention programs.

Duke University researchers offered a helping hand in a review article in the April 7 online Pediatrics, estimating the incremental lifetime direct medical cost of childhood obesity. Their economic model showed a $19,000 incremental lifetime medical cost of an obese child relative to a normal-weight youth.

Ludwig, who directs the New Balance Foundation Obesity Prevention Center Boston Children’s Hospital, provides insights into the next steps.

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Is it time to expand anti-obesity programs beyond schools?

heavy child running ShutterstockSchools have manned the front lines in the battle against childhood obesity. Through the Healthy, Hunger-Free Kids Act of 2010, First Lady Michelle Obama has promoted low-cal lunches, fresh produce and more. Now, she hopes to ban junk food and soda marketing in schools.

Are these efforts enough to turn the tide? Offering healthy foods and promoting physical activity at school may not be enough to negate the impact of other unhealthy influences in students’ homes and neighborhoods, according to Tracy Richmond, MD, MPH, of Boston Children’s Hospital’s Division of Adolescent Medicine.

Richmond recently published a study in PLOS One that looked at how a school’s physical activity or nutrition resources might influence fifth grade students’ body mass index (BMI).

The study focused on 4,387 students in Birmingham, Ala., Los Angeles and Houston. “We wanted to find out if certain schools look ‘heavier’ because of their composition—meaning that kids at higher risk of obesity, like African American girls or Hispanic boys, cluster within certain schools—or whether something structural in the school influences BMI, like the facilities or programs offered,” explains Richmond.

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The obesity-asthma connection: A link in the innate immune system?

asthmatic airway
Obesity may set off innate immune factors that inflame the lungs.

Both asthma and obesity have surged in recent decades, and a growing body of literature is linking the two conditions. Various explanations have been proposed: One recent study suggests that hormonal factors in obesity may regulate airway diameter; another suggests that obesity activates asthma-related genes.

“Why obesity predisposes a person to asthma has been a real puzzle,” says Dale Umetsu, MD, PhD, who recently researched the problem with Hye Young Kim, PhD, and other colleagues in the Division of Allergy and Immunology at Boston Children’s Hospital. “Our goal was to find the connection between these two problems, which occur in both children and adults, and to explore possible new treatments.”

The team’s research indicates that obesity alters the innate immune system—the body’s first responder to infection—in several ways, resulting in lung inflammation. Published earlier this month in Nature Medicine, their work also suggests a completely new, “druggable” approach to treating patients with obesity-associated asthma, for whom standard asthma drugs often work poorly.

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Preschool obesity is down, but Feds need to do more

Young child on scale ShutterstockThe scales may not be tipping up quite so precipitously for some low-income preschoolers. So says a recent report from the Centers for Disease Control and Prevention (CDC). Bucking the previous trend, 19 states saw small decreases in obesity rates among preschoolers between 2008 and 2011, while rates held steady in another 20 states. Is this cause for celebration, cautious optimism or concern?

Perhaps all of the above, says David Ludwig, MD, PhD, director of the New Balance Foundation Obesity Prevention Center Boston Children’s Hospital. “The report is a small, but encouraging, sign after nearly half a century of bad news.”

The latest data, along with several other reports, are raising hopes that the era of continually rising obesity rates may be drawing to a close. But most epidemics aren’t halted by a small crook in the prevalence curve. In fact, containing the obesity curve will require more muscle from federal decision makers, Ludwig contends.

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