Researchers in the Faculty of Medicine have determined why inflammation in the hypothalamus can cause excess weight gain.
Dr. Michiru Hirasawa is a professor of neurosciences in the Division of BioMedical Sciences at Memorial University.
She is interested in how the brain controls appetite and body weight.
A recent paper, published in the Proceedings of the National Academy of Sciences, is the culmination of her nearly 15 years of study on the subject.
Explaining opposite outcomes
When we get sick, through infection or chronic disease, inflammation occurs and that includes the brain, says Dr. Hirasawa.
“When the brain is inflamed, you get fever, lethargy, loss of appetite and loss of body weight. That’s usually what inflammation is associated with,” she said. “However, in the last two decades, it was found that inflammation also happens during obesity and causes increased body weight and appetite. No one really had a clear answer to why it can cause two opposite outcomes. Our study provides an explanation for the conundrum.”
Her research revealed an inflammatory molecule, prostaglandin E2 (PGE2), is produced in the hypothalamus by high-fat diets and directly activates a group of appetite-inducing melanin-concentrating hormone neurons.
In contrast, high levels of PGE2, as seen during infections, were found to inhibit the same neurons.
Her research group used genetic tools to remove the receptor for PGE2 in melanin-concentrating hormone neurons of mice to block its activation.
This protected the mice from obesity and fatty liver, even when fed a high-fat diet.
Dr. Hirasawa says since body weight regulation is a complex process, there are likely other reasons why inflammation can cause both weight gain and loss, but her research provides at least one of those answers.
“If we target this mechanism as a treatment of obesity, what are the long-term impacts?”
She and her team use animal models because it’s difficult to pinpoint a cause or result in humans when there are so many variables in our lifestyles.
“With animal models, we can manipulate very specific factors and see the result. Our study showed that targeting PGE2 signaling may be a promising path toward treatments for obesity, but we need to be cautious with this approach because PGE2 has many important functions. There may be unwanted side effects if you block PGE2 for a long time.”
Her research group is now studying the mice created for the study to see what other phenotypes, or characteristics, they have.
“MCH has also been linked to memory, mood and sleep,” she said. “If we target this mechanism as a treatment of obesity, what are the long-term impacts?”
Although many students and research assistants were involved throughout past 15 the years, Dr. Hirasawa gives special credit to two.
“This project has been passed on from generation to generation of students, but two in particular hardworking and talented PhD students, Lisa Fang and Victoria Linehan, played a very important role in the project.”