In recent years, researchers have been puzzling over an intriguing question about obesity: Is it caused solely by how many calories you consume and metabolize? Or does the timing of when you eat also impact body weight and metabolism?
Johns Hopkins University Center Director: Jeanne Marie Clark, M.D., M.P.H.
In recent years, researchers have been puzzling over an intriguing question about obesity: Is it caused solely by how many calories you consume and metabolize? Or does the timing of when you eat also impact body weight and metabolism?
To delve further into that question, scientists at Johns Hopkins University used novel approaches to better understand the role of time-restricted feeding on obesity and cardiometabolic health.
In the basic science project, researchers confirmed that restricting the feeding time for obese mice protects them against weight gain and some metabolic effects like glucose tolerance, which is partly due to the up-regulation of a molecule called AMP-activated protein kinase (AMPK), said Center Director Jeanne Marie Clark, M.D., M.P.H.
But in the clinical science project, time-restrictive feeding in humans didn’t seem to cause weight loss or improve glucose, blood pressure or lipids. The population science project showed similar results. It used a mobile app to look at eating and sleeping patterns in a large group, but again, those patterns did not seem to influence weight changes.
While the results were the opposite of what researchers had hypothesized, they're important because they show that time-restrictive feeding for losing weight doesn't live up to its early promise.
Our research adds to the literature and helps us move away from the time-restrictive feeding option by saying, ‘It's not really the time that you eat the food, it's what you eat,’ Clark said. The quality of the diet and the calories still are the biggest drivers of weight.
She commended the American Heart Association for putting together a research network that was unifieddespite being four teams with completely different focuses and approaches to such a big problem.
We received a lot of good feedback from the other investigators and especially from the Oversight Advisory Committee, who were really effective. I was impressed by how engaged and motivated they were to produce the best science possible, she said.
Center Director: Jeanne Marie Clark, M.D., M.P.H.
New York University Medical Center Center Director: Ann Marie Schmidt, M.D.
Researchers at New York University (NYU) zeroed in on two questions countless people ask themselves every day: Why is it so hard to lose weight? And why is it also very hard to keep the weight off?
To find answers, they looked at one potential problem area: The body's natural brakes that block energy use after weight loss, including the receptor for advanced glycation endproducts (RAGE).
NYU scientists modified the receptors in both mice and humans and found potential benefits for blocking the RAGE pathway either through medicine or genetic tools, said Center Director Ann Marie Schmidt, M.D.
There's every reason to believe that very exciting biomarkers and pharmaceuticals for weight loss success will come from that, she said.
In the population science project, researchers looked beyond one-size-fits-all approaches to diets and weight loss and focused on alternative techsupported behavioral weight loss programs.
People have a broad spectrum of risks for obesity, she said. It's very likely we will have to tailor weight loss to particular people now and advise them individually about what's the best recipe for them to lose weight and keep it off.
As productive as the research was, Schmidt said the AHA's SFRN on Obesity also fired up NYU fellows and scientists to make future breakthroughs.
Many times, when the grant’s over, everybody goes their own way but that’s not the case here. It's really synergized and brought people together and energized them to continue to work together. It sets up a lot of future directions, and you can attribute a lot of that to the encouragement and insightful suggestions the Oversight Advisory Committee gave us, she said.
Hats off to the AHA for creating such a wonderful network and setting a tone for successful research. I'm thrilled to be able to take part in it.
Center Director: Ann Marie Schmidt, M.D.
University of Alabama at Birmingham Center Director: W. Timothy Garvey, M.D.
Scientists already know mothers with obesity tend to give birth to children with obesity, who often pass it on to the next generation. But they don't know why – or how to stop the endless cycle.
At the University of Alabama at Birmingham (UAB), researchers looked closely at events in the womb to learn how these mechanisms help determine body weight in children and increase risk for diabetes and heart disease.
The basic science project studied how different forms of stress during pregnancy change the metabolism of rats when they become adults. UAB scientists fed the mothers different types of diets to learn more about how that impacts pathways of metabolism as well as satiety hormones, which lead to sensations of hunger or of feeling full.
In the clinical science project, researchers delved deep into how a mother's pregnancy affects the first three months of a human baby's life, including their metabolism, body composition and insulin resistance.
The third project, focused on population science, shifted attention to the mother-child pairs to understand how a mother's weight, diabetes and genes contribute to the inter-generational transmission of obesity and related health risks.
The results of all three projects told a similar story, said Center Director W. Timothy Garvey, M.D.
The main message is that we really need to pay more attention to maternal health prior to conception, and not just focus on risk factors for cardiovascular disease in adulthood, he said. If we can get mothers to achieve a healthier body weight before they get pregnant, we can mitigate some of the generational transmission of obesity.
The UAB fellows who worked on the SFRN benefited from a very creative multidisciplinary training experience. It made them think beyond the limits of their own research and gave them a broad translational reach, Garvey said.
I've taken part in research projects before, but not one with this level of breadth of research, with all the projects interrelated and synergistic, he said. The American Heart Association has designed a research network where the projects are greater together than the sum of their individual parts.
Center Director: W. Timothy Garvey, M.D.
Vanderbilt University Medical Center Center Director: Kevin Niswender, M.D., Ph.D.
Before you can develop precision medicine, first you must know precisely what you're dealing with.
At Vanderbilt University, researchers set out to better understand the nuts and bolts of glucagonlike peptide 1 receptor (GLP1-R), which could be the key to fighting obesity and improving cardiometabolic health.
In the basic science project, researchers used mouse models to develop important preliminary data about genetics and molecular pharmacology that could, one day, translate into a simple pill for humans to manage their weight.
In the clinical science project, scientists looked at GLP1-R drugs to find new ways of decreasing inflammation and other cardiometabolic disorders. For the population science project, researchers studied electronic health records of more than 900,000 people treated at Vanderbilt to shed new light on the intersection of GLP1-R, genetics, obesity and a wide range of health problems. (All of the records were randomized and participants were de-identified.)
We're really beginning to get a much more nuanced picture of what the clinical phenotypes of obesity are, and how precision medicine can improve outcomes, said Center Director Kevin Niswender, M.D., Ph.D.
We have one group that is very obese but also seems to be very metabolically healthy and may not need a lot of resources. Another group may not be as obese but has the features of people who develop severe terrible cardiovascular and metabolic disease. In that case, using algorithms, we'd be able to intervene much, much earlier, before it's too late, he said.
Niswender commended the AHA for paving the way for a revolution in obesity prevention and treatment.
It's an incredibly brilliant concept, so well-managed and executed. A more typical funding mechanism is a single investigator swimming upstream in a sea of funding, but this SFRN concept pulls people together with very different skill sets so they work together and create powerful synergy, new ideas and creativity, he said.
When it comes to obesity, we're in a brand-new day, he said. And I think this SFRN is going to steamroll the way toward precision medicine and targeted therapies to reduce this burden of cardiovascular disease.
