Free radicals crucial to suppressing appetite, study finds

This image shows satiety promoting melanocortin neurons (green) in the hypothalamus, some of which are activated (red nuclei) after treatment. Credit: Tamas Horvath, Yale University

Obesity is growing at alarming rates worldwide, and the biggest culprit is overeating. In a study of brain circuits that control hunger and satiety, Yale School of Medicine researchers have found that molecular mechanisms controlling free radicals—molecules tied to aging and tissue damage—are at the heart of increased appetite in diet-induced obesity.

Published Aug. 28 in the advanced online issue of Nature Medicine, the study found that elevating free radical levels in the hypothalamus directly or indirectly suppresses in obese mice by activating satiety-promoting melanocortin neurons. Free radicals, however, are also thought to drive the aging process.

"It's a catch-22," said senior author Tamas Horvath, the Jean and David W. Wallace Professor of Biomedical Research, chair of comparative medicine and director of the Yale Program on Integrative Cell Signaling and Neurobiology of Metabolism. "On one hand, you must have these critical signaling molecules to stop eating. On the other hand, if exposed to them chronically, free radicals damage cells and promote aging."

"That's why, in response to continuous overeating, a cellular mechanism kicks in to suppress the generation of these free radicals," added lead author Sabrina Diano, associate professor of Ob/Gyn, neurobiology and comparative medicine. "While this free radical-suppressing mechanism—promoted by growth of intracellular organelles, called peroxisomes—protects the cells from damage, this same process will decrease the ability to feel full after eating."

After the mice ate, the team saw that the neurons responsible for stopping overeating had high levels of free radicals. This process is driven by the hormone leptin and glucose, which signal the brain to modulate food intake. When mice eat, leptin and glucose levels go up, as does free radical levels. However, in mice with diet-induced obesity, these same neurons display impaired firing and activity (leptin resistance); in these mice, levels of free radicals were buffered by peroxisomes, preventing the activation of these neurons and thus the ability to feel sated after eating.

According to Horvath and Diano, the crucial role of free radicals in promoting satiety as well as degenerative processes associated with aging may explain why it has been difficult to develop successful therapeutic strategies for without major side effects. Current studies address the question of whether, under any circumstance, satiety could be promoted without sustained elevation of in the brain and periphery.

More information: Nature Medicine, DOI: 10.1038/nm.2421

Related Stories

Researchers use banned herbicide to prolong worms' life

date Dec 08, 2010

It sounds like science fiction – Dr. Siegfried Hekimi and his student Dr. Wen Yang, researchers at McGill's Department of Biology, tested the current "free radical theory of aging" by creating mutant worms that had increased ...

Free radicals maybe good for you

date Feb 28, 2011

Fear of free radicals may be exaggerated, according to scientists from Karolinska Institutet. A new study, published in The Journal of Physiology, shows that free radicals act as signal substances that cause the heart to ...

Free radical cell death switch identified

date Jun 01, 2006

U.S. scientists say they've found a molecular pathway that might cause stroke, diabetes, heart and neurodegenerative disease and even the aging process.

New finding may help baby boomers get buff

date Jan 04, 2010

If you're an aging baby boomer hoping for a buffer physique, there's hope. A team of American scientists from Texas and Michigan have made a significant discovery about the cause of age-related muscle atrophy that could lead ...

Recommended for you

'Google Maps' for the body: A biomedical revolution

date 4 hours ago

A world-first UNSW collaboration that uses previously top-secret technology to zoom through the human body down to the level of a single cell could be a game-changer for medicine, an international research ...

New compounds could offer therapy for multitude of diseases

date 5 hours ago

An international team of more than 18 research groups has demonstrated that the compounds they developed can safely prevent harmful protein aggregation in preliminary tests using animals. The findings raise hope that a new ...

Novel nanoparticle therapy promotes wound healing

date Mar 26, 2015

An experimental therapy developed by researchers at Albert Einstein College of Medicine of Yeshiva University cut in half the time it takes to heal wounds compared to no treatment at all. Details of the therapy, ...

User comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.