Why do certain foods lead to overeating and obesity?

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Postdoc Austin Korgan at The Jackson Laboratory.

JAX postdoctoral associate Austin Korgan, Ph.D., has received a Ruth L. Kirschstein National Research Service Award from the National Institutes of Health (NIH) to support his research studying obesity. Korgan is using the award to understand how what we eat changes our brains, and how those changes in our brains, in turn, change how much we eat.

 Obesity affects almost 100 million people in the United States – about 40% of the population. It contributes to increased risk of diabetes, heart disease, hypertension, clinical depression, osteoarthritis and some cancers. Obesity is, quite simply, having a body weight that is higher than what is considered healthy. The underlying causes of obesity are complex: there are genetic and environmental factors that put some people at much greater risk of gaining excess weight. Regardless of the causes, the primary driver of obesity is excessive caloric intake – eating too much. So a key question is: what controls how much we eat?

 Kristen O'Connell, Ph.D.Kristen O’Connell’s research program is focused on understanding the impact of diet, body weight and peripheral hormone signaling on neuronal excitability and plasticity in the hypothalamus and other brain regions associated with the regulation of food intake and body weight.kristen-oconnell

Korgan, working with JAX Assistant Professor Kristen O'Connell, Ph.D., is particularly interested in the brain region that controls food-seeking behavior, the hypothalamus. Like humans, mice that eat a diet high in animal-derived fats tend to gain weight, modeling the essence of obesity. To determine how diet affects the mechanisms underlying food-seeking and food intake, Korgan has measured the activity of neurons in the hypothalamus. He discovered that there is more neuronal activity in mice that ate a high-fat diet compared to mice that ate a standard diet. Higher neuronal activity in the hypothalamus causes those mice to eat more. Korgan found that as few as two days of eating a high-fat diet — equivalent to 2-3 months for humans — was enough to change the neuronal activity in the hypothalamus. His findings show that even short-term dietary choices can have long-term, perhaps life-long, impacts on how much we eat.

Now Korgan wants to understand how those neurons in the hypothalamus remember what the mouse ate, even when the diet changes from high-fat back to the standard. With the support of his fellowship, he will look at how diet changes the genes that are active in the neurons: which genes become active after mice eat high-fat food and which genes stay active after high-fat diet, no matter what the mice eat. By determining the genes that respond to diet, Korgan may be able to determine ways of making neurons forget the high-fat diet and return the mouse’s food-seeking behavior back to its baseline level. 

“This NRSA fellowship will allow us to continue probing circuit, transcript, and gene level pathways in the search for risk-factors and treatments to obesity and associated co-morbidities,” said Korgan. “I am so happy to have this support from the NIH.”

“We are incredibly grateful for this support from the NIH, which will allow Austin to integrate his on-going training as a systems neuroscientist with JAX’s strength in mammalian genetics to investigate obesity at the genetic and circuit level," says O'Connell. "His studies have the potential to yield new insights into the function of the central nervous system in obesity and its associated comorbidities. Austin is a very talented and creative scientist and I am very excited to see the new directions this work takes him.”