Bioethics Blogs

Tracing the Neural Circuitry of Appetite

Caption: A stylized image of the MC4R-expressing neurons (in red) within the brain’s PVH, which is the “heart of hunger”
Credit: Michael Krashes, NIDDK, NIH

If you’ve ever skipped meals for a whole day or gone on a strict, low-calorie diet, you know just how powerful the feeling of hunger can be. Your stomach may growl and rumble, but, ultimately, it’s your brain that signals when to start eating—and when to stop. So, learning more about the brain’s complex role in controlling appetite is crucial to efforts to develop better ways of helping the millions of Americans afflicted with obesity [1].

Thanks to recent technological advances that make it possible to study the brain’s complex circuitry in real-time, a team of NIH-funded researchers recently made some important progress in understanding the neural basis for appetite. In a study published in the journal Nature Neuroscience, the researchers used a variety of innovative techniques to control activity in the brains of living mice, and identified one particular circuit that appears to switch hunger off and on [2].

The circuit involves a group of neurons expressing a protein on their surface called the melanocortin-4 receptor (MC4R). What’s interesting is that the gene that codes for MC4R has been known for years to play an important role in obesity. Mutations in MC4R are rare, but can cause inherited obesity in humans. Also, mice that lack functional versions of the gene overeat and grow extremely obese, ballooning to double their normal weight.

Last year, Michael Krashes, now with NIH’s National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); Bradford Lowell of Harvard Medical School and Beth Israel Deaconess Medical Center, Boston; and their colleagues discovered MC4R-expressing neurons in the paraventricular nucleus of the hypothalamus (PVH), a very specific region of the brain known for its role in energy balance and hunger [3].

The views, opinions and positions expressed by these authors and blogs are theirs and do not necessarily represent that of the Bioethics Research Library and Kennedy Institute of Ethics or Georgetown University.