Under the Hood

Learning To Control The Brain's Fat Hormone May Lead To Drug For Healthy Weight Loss

Understanding Fat
Understanding how the brain processes fat in the brain improves outlook for obese people with defected hunger signals. Photo courtesy of Flickr, Laura Lewis

Leptin has been called the “obesity hormone” for the way it appears excessively in people who are overweight or obese. However, produced by fat cells, it’s really meant to inhibit hunger, which is why when scientists discovered it in 1994, it prompted widespread hope that it would become an effective weight loss treatment. Now, a new study from researchers at the Instituto Gulbenkian de Ciência in Portugal and Rockefeller University builds on this understanding by exposing how the hormone facilitates communication between the brain and the stomach.The international team’s findings, published in the journal Cell, may lead to anti-obesity treatments in the future.

"These studies add an important new piece to the puzzle that enables leptin to induce fat loss," said the study’s co-author Jeffrey Friedman, a researcher from Rockefeller University, in a press release. Leptin controls weight by telling the brain how to regulate the food a person is eating, and controlling how fast or slow their metabolism breaks down fat.

As leptin levels rise, your appetite falls and your metabolism increases. The opposite is true when their levels fall; your appetite rises and your metabolism slows. Friedman and his colleagues combined their efforts with researchers in Portugal to create a technique to figure out exactly how this system works with the brain, and how they might manipulate it.

"We dissected these nerve fibers from mouse fat, and using molecular markers, identified these as sympathetic neurons," said the study’s co-author Ana Domingos, a researcher from Instituto Gulbenkian de Ciência, in a press release. Next, the team used an "ultra-sensitive imaging technique" on the living mouse’s fat tissue and observed that fat cells could be controlled from those sympathetic neurons in the brain.  Ultimately, they found that a blood supply travels through the nerves to feed the fat tissue. When they stimulated these neurons linked to the fat tissue, it led to the breakdown of fat.

"We used a powerful technique called optogenetics, to locally activate these sympathetic neurons in fat pads of mice, and observed fat breakdown and fat mass reduction," Domingos said. "The local activation of these neurons leads to the release of norepinephrine, a neurotransmitter that triggers a cascade of signals in fat cells. Without these neurons, leptin is unable to drive fat-breakdown."

According to Domingos, the study should serve as "new hope" for treating obese people who are insensitive and resistant to leptin, which means they’re unable to receive signals from leptin properly. The typical modern lifestyle that leads to leptin resistance is a combination of a fast food diet, little or no physical activity, high levels of stress, and not enough sleep, according to internist Dr. Leo Galland.

Constantly ignoring leptin signals that tell the body it’s full trains the body to eventually ignore the signals altogether. Leptin resistance is prevalent in most obese people and is the reason they can continue to eat despite having no appetite. Now that researchers have learned how to turn on leptin’s fat-burning switch, they could help retrain the brain and fat tissue to communicate successfully again, so that when a person is full they listen to their body instead of simply ignoring it.

Source: Domingos AL, Zeng W, Pirzgalska RM, et al. Sympathetic Neuro-Adipose Connections Mediate Leptin-Drive Lipolysis. Cell. 2015.

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