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THURSDAY, April 27, 2017 (HealthDay News) -- Even if obesity is "in your genes," regular exercise can help keep extra pounds at bay, a new study suggests.

Researchers found that when people carried a particular gene variant that raises obesity risk, regular exercise seemed to reduce the effects of their DNA -- by about one-third.

The gene in question is known as FTO. Studies show that people with a particular variant of the gene have a heightened risk of obesity.

But the gene's effects are not huge, or written in stone. Research has found that people who carry two copies of the FTO variant (one inherited from each parent) weigh about 6.5 pounds more than non-carriers, on average.

The new findings underscore one way to counter the gene's impact: Exercise.

"There are genes that appear to directly impact weight, but the effects are small," said lead researcher Mariaelisa Graff, of the University of North Carolina at Chapel Hill. "You still have a lot of choice over your behavior."

The study results are not exactly surprising, according to Dr. Timothy Church, an obesity researcher who was not involved in the work.

"This shows, once again, that genes are not your destiny," said Church. He is a professor of preventative medicine at Louisiana State University's Pennington Biomedical Research Center.

Church said regular exercise is particularly key in preventing excess weight gain in the first place -- and in keeping the pounds off after someone loses weight.

Exercise is less effective in helping obese people shed weight, Church said. Diet changes are the critical step there.

But the bottom line is that exercise matters, regardless of your genes, according to Dr. Chip Lavie, of the John Ochsner Heart and Vascular Institute, in New Orleans.

Lavie, who was not involved in the study, pointed to findings from his own research.

"[We] have published data that suggests the main cause of increasing obesity over the past five decades is the dramatic decline in physical activity," he said.

Gym memberships aside, Americans these days are less active at work, at home (through housework) and during leisure time, according to Lavie.

And the benefits of exercise go beyond weight control, he stressed. Physical activity boosts people's fitness levels -- which, Lavie said, is critical in preventing heart disease and living a longer, healthier life.

The new findings are based on over 200,000 adults, mostly of European descent, who'd taken part in previous health studies.

Graff and her colleagues analyzed information on their weight and exercise habits, and looked at how those factors "interacted" with 2.5 million gene variants.

FTO is the gene that is most strongly linked to obesity, Graff said.

And overall, her team found, active people who carried the obesity-linked FTO variant appeared more resistant to its effects than sedentary people.

On average, exercise weakened the variant's effects by about 30 percent, the researchers reported in the April 27 issue of PLOS Genetics.

There were some hints that exercise also affected some other weight-related genes. But the only clear relationship was with the FTO variant, according to Graff.

That, she noted, could be related to the broad way the study looked at exercise. The 23 percent of people who were least active were considered "inactive," while everyone else was deemed "active."

Church said he thinks research into the genetics of body weight will increasingly become useful.

If certain gene variants affect people's response to a low-carb diet or aerobic exercise, for example, that could help in "tailoring" weight-loss plans, he suggested.

"The science is rapidly evolving," Church said, "and there's still a lot to learn. But I think that's the direction this is going."

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No Excuses: Exercise Can Overcome the 'Obesity Gene' - Glens Falls Post-Star

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Goal is vaccine that targets inflammation in joints

Using CRISPR technology, a team of researchers led by Farshid Guilak, PhD, at Washington University School of Medicine in St. Louis, rewired stem cells' genetic circuits to produce an anti-inflammatory arthritis drug when the cells encounter inflammation. The technique eventually could act as a vaccine for arthritis and other chronic conditions.

Using new gene-editing technology, researchers have rewired mouse stem cells to fight inflammation caused by arthritis and other chronic conditions. Such stem cells, known as SMART cells (Stem cells Modified for Autonomous Regenerative Therapy),develop into cartilage cells that produce a biologic anti-inflammatory drug that, ideally, will replace arthritic cartilage and simultaneously protect joints and other tissues from damage that occurs with chronic inflammation.

The cells were developed at Washington University School of Medicine in St. Louis and Shriners Hospitals for Children-St. Louis, in collaboration with investigators at Duke University and Cytex Therapeutics Inc., both in Durham, N.C. The researchers initially worked with skin cells taken from the tails of mice and converted those cells into stem cells. Then, using the gene-editing tool CRISPR in cells grown in culture, they removed a key gene in the inflammatory process and replaced it with a gene that releases a biologic drug that combats inflammation.

The research is availableonline April 27 in the journal Stem Cell Reports.

Our goal is to package the rewired stem cells as a vaccine for arthritis, which would deliver an anti-inflammatory drug to an arthritic joint but only when it is needed, said Farshid Guilak, PhD, the papers senior author and a professor of orthopedic surgery at Washington University School of Medicine. To do this, we needed to create a smart cell.

Many current drugs used to treat arthritis including Enbrel, Humira and Remicade attack an inflammation-promoting molecule called tumor necrosis factor-alpha (TNF-alpha). But the problem with these drugs is that they are given systemically rather than targeted to joints. As a result, they interfere with the immune system throughout the body and can make patients susceptible to side effects such as infections.

We want to use our gene-editing technology as a way to deliver targeted therapy in response to localized inflammation in a joint, as opposed to current drug therapies that can interfere with the inflammatory response through the entire body, said Guilak, also a professor of developmental biology and of biomedical engineering and co-director of Washington Universitys Center of Regenerative Medicine. If this strategy proves to be successful, the engineered cells only would block inflammation when inflammatory signals are released, such as during an arthritic flare in that joint.

As part of the study, Guilak and his colleagues grew mouse stem cells in a test tube and then used CRISPR technology to replace a critical mediator of inflammation with a TNF-alpha inhibitor.

Exploiting tools from synthetic biology, we found we could re-code the program that stem cells use to orchestrate their response to inflammation, said Jonathan Brunger, PhD, the papers first author and a postdoctoral fellow in cellular and molecular pharmacology at the University of California, San Francisco.

Over the course of a few days, the team directed the modified stem cells to grow into cartilage cells and produce cartilage tissue. Further experiments by the team showed that the engineered cartilage was protected from inflammation.

We hijacked an inflammatory pathway to create cells that produced a protective drug, Brunger said.

The researchers also encoded the stem/cartilage cells with genes that made the cells light up when responding to inflammation, so the scientists easily could determine when the cells were responding. Recently, Guilaks team has begun testing the engineered stem cells in mouse models of rheumatoid arthritis and other inflammatory diseases.

If the work can be replicated in animals and then developed into a clinical therapy, the engineered cells or cartilage grown from stem cells would respond to inflammation by releasing a biologic drug the TNF-alpha inhibitor that would protect the synthetic cartilage cells that Guilaks team created and the natural cartilage cells in specific joints.

When these cells see TNF-alpha, they rapidly activate a therapy that reduces inflammation, Guilak explained. We believe this strategy also may work for other systems that depend on a feedback loop. In diabetes, for example, its possible we could make stem cells that would sense glucose and turn on insulin in response. We are using pluripotent stem cells, so we can make them into any cell type, and with CRISPR, we can remove or insert genes that have the potential to treat many types of disorders.

With an eye toward further applications of this approach, Brunger added, The ability to build living tissues from smart stem cells that precisely respond to their environment opens up exciting possibilities for investigation in regenerative medicine.

Brunger JM, Zutshi A, Willard VP, Gersbach CA, Guilak F. Genome engineering of stem cells for autonomously regulated, closed-loop delivery of biologic drugs. Stem Cell Reports. April 27, 2017.

This work was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases and the National Institute on Aging of the National Institutes of Health (NIH), grant numbers AR061042, AR50245, AR46652, AR48182, AR067467, AR065956, AG15768, OD008586. Additional funding provided by the Nancy Taylor Foundation for Chronic Diseases; the Arthritis Foundation; the National Science Foundation (NSF), CAREER award number CBET-1151035; and the Collaborative Research Center of the AO Foundation, Davos, Switzerland.

Authors Farshid Guilak, and Vincent Willard have a financial interest in Cytex Therapeutics of Durham, N.C., which may choose to license this technology. Cytex is a startup founded by some of the investigators. They could realize financial gain if the technology eventually is approved for clinical use.

Washington University School of Medicines 2,100 employed and volunteer faculty physicians also are the medical staff of Barnes-Jewish and St. Louis Childrens hospitals. The School of Medicine is one of the leading medical research, teaching and patient-care institutions in the nation, currently ranked seventh in the nation by U.S. News & World Report. Through its affiliations with Barnes-Jewish and St. Louis Childrens hospitals, the School of Medicine is linked to BJC HealthCare.

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Stem cells edited to fight arthritis - Washington University School of Medicine in St. Louis

Doctors have long known that genetics can predispose some people to gain weight despite a healthy lifestyle while others seemingly never gain an ounce no matter how much they eat. A new study sheds light on how people can counteract their genetic makeup, even if it's in their DNA to put on more weight than others.

Researchers from University of North Carolina Chapel Hill, the University of Copenhagen and other institutions conducted a meta-analysis examining 60 past genetic studies to see if physical activity could mitigate the effects a genetic predisposition to weight gain.

"Decline in daily physical activity is thought to be a key contributor to the global obesity epidemic," the authors wrote. However, they explained that genetic make-up may also play a role in weight gain for people who are not physically active.

They screened for 2.5 million genetic variants in 200,452 adults and also separated the subjects between those who were physically active -- about 77 percent -- and those who were physically inactive, about 23 percent. The researchers then looked at different markers that would indicate if a person was overweight including their body-mass index, waist circumference and hip-to-waist ratio.

They found those with a genetic variation that predisposed them to gain weight -- called an FTO gene -- had the ability counteract the effects that gene through exercise. By looking at the data they found that those with the FTO gene who were physically active were able to reduce the weight-gain effects associated with the gene by about 30 percent.

Dr. Goutham Rao, chairman of Family Medicine and Community Health at University Hospitals Cleveland Medical Center, said this type of research is key in helping patients better understand their weight and health.

"Despite that sort of bad luck of having a genetic predisposition to obesity if you are physically active ... you're not going to reduce risk of obesity entirely but you reduce it significantly," Rao said.

The mechanism that leads to people with FTO to be predisposed to gain weight is still not fully understood, but Rao said it's key to give people encouragement that taking healthy steps has an effect even if they haven't reached their goal weight.

"The message is to be sympathetic," Rao said. Explaining he tells frustrated patients, "if you weren't doing your best you would weigh a lot more and be much less healthy."

Dr. Kevin Niswender, associate professor of medicine, molecular physiology and biophysics at Vanderbilt University Medical Center, said the study took on the "really interesting question" of if people can counteract their genetics through their lifestyle.

"This study definitively confirms that lifestyle has an impact," he said.

During their research the team also discovered 11 new genetic variants that likely predispose a person to weight gain and they said more may be found through similar studies.

"In future studies, accounting for physical activity and other important lifestyle factors could boost the search for new obesity genes," said Mariaelisa Graff of the University of North Carolina at Chapel Hill, the lead author of the study. "To identify more genes whose effects are either dampened or amplified by physical activity, we need to carry out larger studies with more accurate measurement of physical levels."

Niswender said finding new variants that indicate predisposition for weight gain can help give a better understanding of the complex mechanisms behind obesity.

"For a long time we've been searching for this gene, the gene that causes obesity and it's just not like that," Niswender."there are a bunch of genes that cause obesity and the effect of each gene variant is really quite small."

Graff said more study should need to be done to get more accurate measurements of the participants' physical activity. The researchers classified those as having a sedentary job, commute and leisure time as "inactive" while everyone else was declared physically active. Additionally, the study was done primarily in people of European descent, so the findings may not be be easily extrapolated to other groups.

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Exercise can help offset effects of 'fat gene,' study finds - ABC News

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April 25, 2017 -A team from the University of Virginia School of Medicine has developed a quicker way to examine the impact of gene mutation on patient health, potentially changing the way cancer labs conduct research into precision medicine and personalized therapies.

The methodology, which uses a virus similar to HIV to replace normal genes with specific mutations, may even be speedier and more cost effective than the CRISPR gene editing technology that currently forms the basis for much of the industrys cutting-edge genomics work.

"Every patient shouldn't receive the same treatment. No way. Not even if they have the same syndrome, the same disease," said UVA researcher J. Julius Zhu, PhD, who led the team that created the new technique. "It's very individual in the patient, and they have to be treated in different ways."

The process of understanding and testing a specific mutations impact on disease development and the usefulness of particular therapies has thus far been slow and painful, said Zhu, who holds positions in UVA's Department of Pharmacology and the UVA Cancer Center.

"You can do one gene and one mutation at a time, he said. Even with the CRISPR [gene editing] technology we have now, it still costs a huge amount of money and time and most labs cannot do it, so we wanted to develop something simple every lab can do. No other approach is so efficient and fast right now.

In addition to ramping up the velocity of studying gene mutations, the new approach may be able to reduce failures in the research process by giving researchers a more sensitive, targeted way to stimulate gene activity.

"The problem in the cancer field is that they have many high-profile papers of clinical trials [that] all failed in some way," Zhu said. "We wondered why in these patients sometimes it doesn't work, that with the same drug some patients are getting better and some are getting worse. The reason is that you don't know which drugs are going to help with their particular mutation. So that would be true precision medicine: You have the same condition, the same syndrome, but a different mutation, so you have to use different drugs."

Zhu has already used the method to analyze approximately 50 mutation of the BRaf gene, which has been tied to tumor development and certain neurodevelopmental disorders. He envisions that the technique will also help unlock the secrets of other diseases, such as Alzheimers, cystic fibrosis, and a variety of cancers all of which are top priorities for precision medicine researchers.

As the marketplace for targeted therapies and associated precision medicine technologies approaches the $100 billion mark, techniques that can help cancer researchers accelerate the development of new treatments will continue to be in high demand.

Drastically reducing the time from hypothesis to bedside will likely produce financial benefits for research labs as well as clinical benefits for patients.

You'd need to spend 10 years to do what we are doing in three months, so it's an entirely different scale, said Zhu. Now, hopefully, we can do 40 or 100 of them simultaneously."

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UVA Gene Mutation Research Method Speeds Precision Medicine - Health IT Analytics