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5 questions: Penn neuroscientist examines how the brain controls when and why we eat

Amber Alhadeff is one of five women nationally chosen this year to receive a $60,000 grant from L'Oréal USA as part of its For Women in Science fellowship program.

Penn neuroscientist Amber Alhadeff is one of five women nationally this year chosen to receive a $60,000 grant from L'Oréal USA as part of its Women in Science fellowship program.
Penn neuroscientist Amber Alhadeff is one of five women nationally this year chosen to receive a $60,000 grant from L'Oréal USA as part of its Women in Science fellowship program.Read moreL'Oréal USA

You're hungry. But what does that mean?

What's happening physiologically to cause you to feel hungry?

And can that be changed to fight obesity, diabetes and other metabolic disorders?

Neuroscientist Amber Alhadeff, a postdoctoral researcher in the Biology Department at the University of Pennsylvania, is intrigued by such questions. Her research focuses, in part, on hunger neurons and how they influence what, when and why we eat.

Alhadeff is one of five women nationally chosen this year to receive a $60,000 grant from L'Oréal USA as part of its For Women in Science fellowship program. About 70 percent of L'Oréal's global scientific workforce is female, and the program selects women based on their contributions in STEM — Science, Technology, Engineering and Math — fields.

She spoke to us recently about her work.

What are hunger neurons? Why are they important?

The gut is actually connected to the brain through our nervous system. Hunger neurons are neurons that signal when we haven't eaten for a while – when we've been food-deprived, or perhaps even in the morning after an overnight fast. When they're active, they make us want to eat. That's what makes them important to study. I'm interested in understanding our eating behavior and how the brain controls this behavior.

So, when we're hungry, we eat food. Then, when we eat, signals pass from the gut through this nervous system and ultimately get to the brain. The food is passed through our gastrointestinal tract. It gets to our stomach and our intestines. When our stomach fills with food, there's a mechanical stretch that gets signaled to the brain.

But also, the nutrients get signaled to the brain. That's mostly through the intestines. This is important because if we eat something that's not nutritious, we may want to eat more even if we're full. That's because the nutrient signal will be lacking.  You may get that mechanical stretch of the stomach, but the nutrient signal will be gone.

There used to be a war on fat. Now there's not so much of a war on fat because those calories are satiating. They make us feel full or satisfied.  Often, low-calorie foods and diet foods do not. I'm thinking of super-low-calorie yogurts or cereals. You don't feel as satiated when you eat low-calorie yogurt as when you eat full-fat yogurt.

What are some of the questions you hope to explore and answer?

I'm interested in two things. I'm interested in figuring out exactly how the gut communicates with the brain. Also, I'm interested in how the brain controls the negative feelings we get when we get hungry. We all have experienced that bad feeling when we're hungry.  By that I mean, when you're hungry, you get irritable and maybe a little anxious. And when you eat, you feel better, more like yourself again. I tell people it's kind of like the Snickers commercial – "You're not you when you're hungry." That really describes what we're talking about.

We think — and this is what the L'Oréal grant is supporting – that we have uncovered a population of neurons in the brain that's mediating this feeling. So the future research is to really to get into the nitty-gritty of that and figure out the neural circuits that are involved.

Those negative feelings we get when we're hungry are part of the reason it's so difficult to lose weight. Millions of Americans experience this. It's universally difficult. If we can better understand how to alleviate these negative feelings when you're hungry, it may give insight into how to control our appetite.

Essentially, what I'm trying to do is map connections from the gut to the brain, and also within the brain.

How could this affect our ability to treat metabolic diseases such as obesity, eating disorders, and type 2 diabetes?

By mapping these connections and figuring out how these brain circuits work, we could uncover new targets for the development of treatments for these disorders. There are several drugs now that are approved by the U.S. Food and Drug Administration for weight loss. They target certain molecular pathways between the gut and brain. They help some people lose weight, but overall, they're not that effective. Getting a better understanding of the neural circuits and molecular pathways will allow us to create better drugs.

We could target drugs to try to turn off the hunger neurons, or to increase satiation signaling. This is all broader future directions. But this is what I hope my work will enable.

In addition to supporting your research, what will the L‘Oréal grant help you do?

It will allow me to hire two undergraduate women and mentor them in the lab. I've had really great mentors in the past, and it's really important to me to pass that along to the younger generation of female scientists.

As part of the grant, I'll also do some service activities. One thing I'm going to do is speak to local high school women and tell them about what I do and try to garner some excitement for science. I think the younger we do this, the better.

My own interest in science was prompted when I started running marathons more than 10 years ago. At the time, I realized how important what we eat is for performance. I realized how important what we eat is for a lot of human diseases. I became really interested in how the body controls what we eat.

What’s the most amazing or surprising thing you’ve learned so far in your research?

The most striking thing is that there are billions of neurons in the brain, and we can change behavior with only a few hundred neurons. In other words, it only takes a small change in neural activity to influence behavior. I think that's a really powerful thing to know.

We're just learning about how these small changes can affect our behavior. More broadly, the brain controls all our behavior — everything we do and our moods and how we interact with other people. I think that the broader concept of how small changes in the brain can so vastly change behavior is really powerful.