From her laboratory at the Naomi Berrie Diabetes Center, Dr. Lori Zeltser and her team work at the crossroads of developmental neurobiology and the physiology of obesity. In particular, they are studying how developmental processes in the brain impart long-lasting effects on physiological traits in the body, such as food intake, energy expenditure, body weight, and obesity.
To that end, Dr. Zeltser’s team is pursuing several avenues of research. For example, they are looking at how the risk of obesity or diabetes is increased by exposure to certain conditions in utero. They also are studying how a combination of factors (including genetics, calorie restriction, and psychological stress) can trigger anorexia nervosa in adolescence.
Another line of research focuses on a different developmental problem—childhood obesity—a growing public health issue. Recent studies indicate that childhood obesity may be established as early as five years of age. Dr. Zeltser’s lab is looking to see whether intervention in childhood can delay, mitigate, or even prevent the consequences of childhood obesity, and, if so, to determine the right time to intervene.
Dr. Zeltser’s findings to date have been both important and surprising. Using mice genetically engineered to overeat and to exhibit early-onset obesity and diabetes, Dr. Zeltser’s lab has identified a brief window of opportunity for intervention that produces permanent reductions in obesity, independent of changes in food intake. These findings may lead to a change in approaches to treating childhood obesity.
Dr. Zeltser received her undergraduate degree from Princeton University and her PhD from Rockefeller University;she was a 2005 Naomi Berrie Fellow from Columbia University’s Department of Biochemistry. She recently talked about how her interest in the development of the brain led to her current research in childhood obesity. What follows is an edited version of her interview.
Please tell us what you are learning about childhood obesity.
Dr. Zeltser: We found that early-onset obesity in mice leads to a structural defect in brown adipose tissue (“BAT,” or “brown fat”) that impairs BAT’s ability to burn energy. This reduced capacity to burn energy, at the same time that the animal is overeating, creates a vicious cycle that exacerbates the initial levels of obesity. When we reduce obesity in our mice through caloric restriction from a young age, however, the BAT structure is dramatically improved and the body is able to burn more calories. And this increased capacity to burn energy is maintained for a long time, even after the mice are allowed to resume overeating.
We think we have tapped into a process that also affects children who develop obesity from a very young age. If so, more aggressive diet and exercise programs targeted at this population could lead to lasting improvements in body weight and related health problems.
Can activating brown fat also reduce obesity in adults?
Dr. Zeltser: Recent studies suggest that BAT activity is impaired in obese children and adults. In our model, structural improvements in BAT resulting from caloric restriction were insufficient to increase BAT activity in adults, suggesting that additional factors are required in mature animals. In fact, identifying compounds that can recruit or activate BAT in adults is a major objective of companies looking to develop a new class of anti-obesity therapeutics.
Does this mean that exercise and diet won’t work in the long term for obese older children and teens?
Dr. Zeltser: Study after study of interventions involving diet and exercise in school children show that they do not lead to significant improvements in body weight. I would not say that they are destined not to work. Rather, I think, we just don’t know who would benefit most from intervention and what is the right time and way to intervene. In part, that is because there is almost no basic research in this area that can provide a biological basis for designing cost-effective anti-obesity programs in children.
What about the First Lady’s program “Let’s Move”?
Dr. Zeltser: I think it’s fantastic that Michelle Obama’s programs have increased awareness of childhood obesity, promoted better eating habits, and increased physical activity. It’s a public health message that is desperately needed, and one that can lead to long-term and broad-based improvements in the health of our nation. However, it takes many years to see results from these types of behavioral changes. My research is focused on helping those children who might benefit from more dramatic interventions today—children who don’t have time to wait.
As a developmental neurobiologist, how did you get interested in childhood obesity?
Dr. Zeltser: Throughout my PhD and postdoctoral training, my work was focused exclusively on basic neuroscience: elucidating fundamental processes involved in early brain development. When I initially started to investigate the long-term consequences of these events, I was focused primarily on effects on molecular or anatomical changes within the brain itself. I wasn’t looking for any real physiological outcome.
Rudy Leibel, the co-Director of the Berrie Center, came to me with the opportunity to apply my expertise in developmental neuroscience to the problem of childhood obesity, and something just clicked within my own brain! At that moment, I realized that this sort of research was exactly what I wanted to do with my career—to study developmental neurobiology in the context of a major health problem. That’s how I got my start.
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This article originally appeared on the Naomi Berrie Diabetes Center website.