Naima Moustaid-Moussa, who recently accepted an NIH appointment to review grant applications, is a leading researcher in the causes of obesity.
Naima Moustaid-Moussa came to Texas Tech University almost four years ago as a senior strategic hire for the College of Human Sciences. Dean Linda Hoover charged Moustaid-Moussa to expand research and increase collaboration in the field of obesity research.
In that time, Moustaid-Moussa has spearheaded the creation of the Obesity Research Cluster, a group of dozens of researchers from several disciplines who study all aspects of obesity, continued a collaboration with an agriculture group at the University of Tennessee looking at biofuel, collaborated with engineering, biological sciences, animal and food science and plant and soil science and medical researchers and received a number of awards and recognitions from within the obesity and nutrition research community.
And in 2014, through the efforts of many people, Hoover created the Department of Nutritional Sciences, for the first time breaking nutrition, diabetes and obesity research away from Hospitality and Retail Management.
The latest recognition for Moustaid-Moussa, who came to Texas Tech from the University of Tennessee and to the United States after earning her doctorate in France, is an invitation to review grant applications for the National Institutes of Health (NIH), one of the most competitive funding sources in the United States because of its rigorous review process.
“Highly respected, dedicated and talented reviewers volunteer their time to provide careful reviews of submitted grants,” said Dr. Nikhil Dhurandhar, chairman of the Department of Nutritional Sciences at Texas Tech. “Due to the responsibility involved in reviewing projects that would potentially have a high impact on society, the reviewers are handpicked for their expertise and scientific acumen. Therefore, an invitation to be a reviewer for NIH is often an acknowledgement of one's scientific expertise and prominence in one's research field.”
Moustaid-Moussa started July 1 as a member of the Clinical and Integrative Diabetes and Obesity Study Section for the NIH. Study sections are composed of experts who provide reviews of the grant applications, discuss their merits and rank the applications. These recommendations are then discussed by the NIH council and director for funding decisions. Moustaid-Moussa will participate in this twice a year for the next six years.
This is her first appointment as a standing member of such a committee for the NIH, though not her first time reviewing NIH grants. She was a peer review committee chair for the American Heart Association and has been a temporary and ad hoc committee member for the NIH and U.S. Department of Agriculture (USDA).
It will not slow down her research. Moustaid-Moussa has a half-dozen studies looking at a variety of factors related to obesity. She has made this work her life's mission, and that includes her research, mentoring graduate and undergraduate students, postdoctorates and junior faculty and helping other researchers answer their questions. So much of what they do is interconnected.
“When you do this kind of basic science, it's trying to solve puzzles,” she said. “One piece of the puzzle might hold the key to many things.”
Obesity Research Cluster
As the co-founder of the Obesity Research Center at the University of Tennessee, Moustaid-Moussa had an idea to increase collaboration: get people talking to each other about their research. When she came to Texas Tech she implemented the same strategy. Within a few months of her arrival the Obesity Research Cluster advisory board was formed.
The board has about 20 people from plant and biological sciences, nutritional sciences, media and communications, biotechnology, engineering, nursing and medicine. From there, they planned faculty seminars and annual research meetings, brought in guest lecturers and created a website and a journal club, all centered on increasing collaborations among obesity researchers.
“The goal was to discuss this idea of creating some kind of resource, some kind of infrastructure where people can share and collaborate on research related broadly to obesity,” Moustaid Moussa said.
In 2014, the university put out a call for research clusters, Moustaid-Moussa led a successful application and the Obesity Research Cluster was official. It received Tier 2 funding, which paid for postdocs and graduate students to help with collaborations; bringing top scientists in obesity to Lubbock to talk about their research and give feedback, which would raise the university's profile; and research seed money for teams to generate preliminary data that would help jumpstart external grant applications.
From there, they've worked to increase collaborations, get more studies published and raise the profile of obesity researchers at Texas Tech, which will help the cluster to grow.
“We cannot just go after major external funding for our obesity cluster,” she said. “We need to show we have a track record of some sort to be competitive.”
The Obesity Research Cluster is reaching outside the university, looking at partnerships with other institutions within the Texas Tech University System, the Texas A&M AgriLife Extension and others.
It remains a labor of love for Moustaid-Moussa; being director of the cluster isn't actually in her job description. She does it because she believes encouraging collaboration is critical in research into obesity and because it is in line with her research, which looks at a variety of contributors to obesity.
Adipocytes, inflammation and genetics
Adipocytes are fat cells. Every human and animal has them, but not every fat cell works the same way in different areas of the body, nor is every fat cell created equal. Fat tissue, Moustaid-Moussa explained, is not composed only of fat cells. It includes stem cells, which can create more fat cells, and immune cells. The fat tissue also has blood vessels that nourish it and helps it communicate with other parts of the body.
Of the fat cells, some expand easily while others don't. More and bigger fat cells are present in obesity, but it's not clear why some people's fat cells expand at differing rates. This could be due to differences in age, genetic factors or different metabolic rates that can be influenced by both genetics and age. Physical activity and diet also play an important role.
“When someone develops obesity, the fat tissue expands,” she said. “It expands in size in part because as those round fat cells grow, they accumulate more lipid.”
Some of those reasons are the commonly known contributors to obesity that change the energy balance toward storing more fat instead of breaking it down. For example, people eat diets rich in calories, especially fat and sugar, which the body converts into lipids and stores in fat cells. Others are a little more complicated. In some people, the high-fat diet can trigger their stem cells to multiply and convert into new fat cells. To explain, Moustaid-Moussa paraphrased a common expression in her field: “The genes load the gun and the environment, like high caloric diets and low physical activity or a sedentary lifestyle, pulls the trigger.”
What that leads to, besides greater obesity, is inflammation-inducing molecules known as cytokines are secreted from the fat tissue into the bloodstream. These molecules can cause the liver to stop responding to insulin and therefore make more glucose; stop muscles from taking in glucose; and dysregulate the pancreas, all of which can lead to high blood sugar and over time Type 2 diabetes and other obesity-related illnesses.
“One of our main hypotheses is that adipose tissue expansion and inflammation is responsible for most disorders associated with obesity through the substances the fat tissue produces that can reach all the organs in the body,” she said.
Besides cytokines, fat cells produce hormones like angiotensin II, known for increasing blood pressure in humans. With grants from the American Heart Association and USDA and using bioengineered mice, Moustaid-Moussa determined this hormone can be produced from fat cells and secreted into the bloodstream, contributing to obesity, inflammation and high blood pressure in mice. When she used angiotensin inhibitors, drugs in use in humans to reduce blood pressure, the mice experienced lower weight, fat mass, inflammation and were better able to handle glucose and protect against diabetes.
Most breast cancer can't be traced to obesity, especially before menopause, but Moustaid-Moussa's newer research direction led her to believe some can, all leading back to these inflammation-causing cytokines from fat cells. To test this hypothesis, graduate and undergraduate students on this project grew fat cells from both mice and humans, obese and not, and grew breast cancer cells, then exposed the breast cancer cells to the media where the fat cells were cultured. The experiment shows fat cells from an obese human have more harmful molecules and create a better environment for the breast cancer cells to grow and get more inflamed.
That is not great news. What is helpful is finding out which dietary factors can help reduce obesity-related diseases – looking at identifying beneficial components from such things as omega-3 fatty acids in fish oil, which are good fats. Omega-3s are full of anti-inflammatory effects, and the experiment showed feeding omega-3s to mice changed the composition of the fat cells, making them smaller, reducing the number of inflammatory cytokines produced and resulting in a lower weight and blood sugar for the mice.
“Even in those mice that had some degree of obesity, omega-3 fatty acids actually improved the metabolism of that mouse,” she said. “It became more healthy, with less inflammation and lower blood glucose and insulin and smaller fat cells.”
When mouse or human fat cells were treated with omega-3 fatty acids before being exposed to breast cancer cells, Moustaid-Moussa's lab found the cancer cells used less glucose and produced fewer inflammatory substances, so they had a harder time growing.
Harnessing the power of biofuels
Before coming to Texas Tech in 2012, Moustaid-Moussa was an obesity researcher at the University of Tennessee Institute of Agriculture. While there she started a project with forestry, plant and food science and agriculture groups to study switchgrass, a perennial bunchgrass native to North America and a major biomass and biofuel crop in the United States that is used in ethanol production. The work is funded by USDA and the Southeast Sungrant Center.
Biofuels, though, provide energy for cars and buildings, not bodies. But Moustaid-Moussa and her collaborators found this weed had other secret powers. When switchgrass is fermented, certain compounds had to be removed from it. Her team took a closer look at those compounds and found they were full of polyphenols or phytochemicals like those found in fruits and vegetables that have antioxidant and anti-inflammatory properties. In exposing fat cells to these discarded compounds, she found they reduce inflammation and lipid accumulation in the cells.
Moustaid-Moussa is now part of this unusual collaboration, even holding a patent, issued in March, on antimicrobial and anti-inflammatory effects of switchgrass extracts.
“That's very exciting because this is an added value to this biomass that is usually going to be wasted, but we can create something out of it,” she said.
She's also working with professors in kinesiology and at the Texas Tech University Health Sciences Center (TTUHSC) on related projects to test potential uses of bioactive food to prevent obesity, diabetes and inflammation. One of these projects, led by a TTUHSC professor, was funded by American River Nutrition Inc. to study beneficial effects of vitamin E derivatives in these diseases.
Finding the humanity in worms
The primary purpose of the Obesity Research Cluster is to enhance collaboration among obesity researchers and create new research opportunities. Finding unique collaborations is one of the best ways to generate knowledge and publish innovative research that will draw external grant funding.
With that in mind, Moustaid-Moussa sought unique partnerships. In looking at the idea of developing an obesity and bioengineering research area, she found a natural partnership with chemical engineering professor Siva Vanapalli. Few if any obesity centers funded by the National Institutes of Health are examining bioengineering.
They're starting with finding ways to use a worm – a nematode named C. elegans, one of the most adaptable species around. This worm is, perhaps surprisingly, an excellent model for humans; human-like genes are functional in the worm, including the genes for fat metabolism and insulin signaling, and worms can get fat. Additionally, the nematode lives only three to four weeks, so scientists can study its entire life cycle and track age-related changes.
“It's a very simple model, but some of the earlier studies on caloric restriction and aging came from studies on the worm,” Moustaid-Moussa said.
The researchers will study how some dietary factors like bioactive compounds in fish oil (omega-3 fatty acids) and tart cherry (anthocyanin compounds) affect the metabolism of fats and their relationship to inflammation and obesity-related oxidative stress. This study will take advantage of a novel microfluidics system that Vanapalli designed and allows them to study worms in a liquid environment. Working with worms is more cost-effective than humans or rodents and can provide information to be tested later in humans.
The research partnership – Moustaid-Moussa, Vanapalli, mechanical engineering professor Jerzy Blawzdziewicz and nutritional sciences professor Shu Wang received a grant last year from the USDA for this study. Additionally, students from nutritional sciences, plant and soil sciences, biotechnology and chemical engineering, as well as the Undergraduate Research Scholar program in the Honors College, are working alongside the professors on this transdisciplinary project.
Brown vs. white fat
Obesity isn't black and white. It turns out fat has a few more shades as well.
Researchers have found humans have two types of fat: white and brown. Well, and there's
also a hybrid of the two, appropriately known as beige, or brite, fat. Brown fat is
“good,” while white fat is “bad,” Moustaid-Moussa said, adding the caveat that white
fat in the right amount can be good; it makes some substances that can reduce inflammation
But white fat also expands and secretes pro-inflammatory substances, so obesity occurs when a subject has more white fat than brown fat and those white fat cells enlarge too much and inflame.
Scientists, including Moustaid-Moussa, are still making sense of the role white and brown fat play in the human body. Brown fat has more mitochondria and is more active metabolically than white fat. Newborns and hibernating animals have more brown fat; its primary use is generating heat.
“Obesity is very complex, and many factors contribute to it,” she said. “In the search for solutions to a disease as complex as obesity, one thing that could help is we need more brown fat and less white fat.”
That much they know. There are still many questions related to brown fat, however, including how it is created and whether white fat can turn into brown fat. Omega-3 fatty acids seem to increase, or at least activate, brown fat in mice, which led to the animal weighing less and having less inflammation. Colder temperatures also lead the development of brown fat; a study found individuals who keep their bedroom temperatures at 66 degrees or cooler may experience less obesity, possibly by activating brown fat.
Another study showed when people who suffer from insomnia wore a cap filled with cool circulating water, they slept almost as easily as people without sleep problems, which Moustaid-Moussa said may be due to activating more brown fat or lowering brain activity by the cold, which helps sleep.
These are specific actions, but she said they don't know yet why some people have more brown fat and thus are less likely to experience obesity. It could be genetic, it could be environmental or it could be interaction between the two. Certainly obesity is complex and many factors can contribute to it. Some research has shown people who are physically active produce a hormone, irisin, that may go into the bloodstream after exercise and activate the brain fat. Moustaid-Moussa also is asking whether some nutrients can increase irisin and mimic the effects of physical activity.
While no researchers have figured out if going from white to brown is possible, there is a third color of fat in the human body as well. Beige fat still has lipids, as white fat does, but more mitochondria, like brown fat, and it's more responsive to cold and other treatments that stimulate brown fat, so it is a brown fat-like cell. She and other scientists believe beige fat may be a link in turning white fat into brown fat.
Moustaid-Moussa is waiting on a grant from NIH to continue her work into brown fat. She wants to understand what activates brown fat proteins and whether brown fat responds to omega-3 fatty acids as it appears to respond to cold or physical activity. Her goal is to find diet and lifestyle changes that can modulate genetic effects to help people cope with obesity, which is more manageable for most people than frequent trips to the doctors.
Other ongoing collaborations related to omega-3 fatty acids include work with researchers from the Center for Biotechnology and Genomics at Texas Tech with professors Rao Kottapalli, Susan San Francisco and Masoud Zabet to identify genes and proteins in mice, humans and worms, which may help explain how omega-3 fatty acids and other nutrients regulate fat metabolism.