The brain-belly connection: Scientists find key genetic triggers in weight-regulating brain cells

The brain-belly connection: Scientists find key genetic triggers in weight-regulating brain cells

The little voice inside your head that tells you to eat, or stop eating, isn’t a little voice — it’s actually a cluster of about 10,000 specialized brain cells. And now, an international team of scientists has found tiny triggers inside those cells that give rise to this “voice,” and keep it speaking throughout life.

The new research, done in fish and mice, can’t yet be applied to humans who eat too much or too little. But it reveals how tiny bits of DNA can have a big influence on how the body regulates appetite and weight. It’s the first documentation of exactly how a brain cell gene involved in weight regulation is controlled.

In a new paper published online this week in the Proceedings of the National Academy of Sciences, and a recent paper in PLoS Genetics, the team reports their discoveries on genetic factors key to the brain cells, or neurons, called POMC cells.

Located deep inside the brain, in a structure called the hypothalamus, the cluster of POMC neurons act as a control center for feelings of fullness or hunger. They take in signals from the body, and send out chemical signals to regulate appetite and eating.

When POMC neurons are absent, or not working correctly, animals and humans grow dangerously obese. Now, the new findings show in animals that the same thing happens when certain genetic triggers inside the POMC cells aren’t working.

The team, led by Malcolm Low, M.D., Ph.D. of the University of Michigan Medical School and Marcelo Rubinstein, Ph.D., of the University of Buenos Aires in Argentina, has studied the POMC system for years.

Their new findings center on the gene inside the cells that generates the appetite-regulating signals — the Pomc gene, short for proopiomelanocortin. But studying the gene itself doesn’t tell the whole story of why and how POMC cells do what they do.

In the two new papers, the team reports how a protein called a transcription factor, and two small stretches of DNA called enhancers, act as triggers for the Pomc gene. All three regulate how often and when the POMC cells use the gene to create the signal molecules that then go out to the body. The transcription factor, called Islet 1, also plays a key role in helping POMC cells form correctly during the earliest stages of the brain’s development, before birth.

“The POMC region is a central node of the brain’s means for regulating body weight, in response to influences from the hormone leptin,” says Low, a professor in the Department of Molecular and Integrative Physiology. “We’re interested in understanding how the Pomc gene is regulated in these neurons, which are a very small population with a big job.”

Probing gene triggers

The discovery reported in PLoS Genetics shows the impact of two

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