Researchers in Hamilton have discovered how to turn back the clock on the body's metabolism, potentially paving the way for people to eat and burn calories like they did when they were teenagers.
They're calling it a possible solution to obesity and a preventative measure for diabetes, one that turns up the body's metabolic rate without the negative side effects of increasing the heart rate or blood pressure.
Published in Nature Medicine Monday, researchers from McMaster University show that by inhibiting the hormone serotonin found in the gut of mice, the body's natural furnace, a lesser-known organ called brown adipose tissue, is more active and burns more calories.
Brown adipose tissue is found near the collar bone, and is also known as brown fat. It has no relation to white fat, the fat stores found all over the body, and was previously thought to only exist in rodents, hibernating animals and children, says the paper's co-author Gregory Steinberg, a professor of medicine at the Michael G. DeGroote School of Medicine.
“Our results are quite striking and indicate that inhibiting the production of [serotonin] may be very effective for reversing obesity and related metabolic diseases including diabetes," Steinberg said.
Brown fat plays an important role in burning calories and increasing a person's basal metabolic rate, the resting rate at which someone burns calories.
Western diet high in fat acts as a 'parking brake' on metabolism
Researchers say a "western diet" high in fat also raises levels of the hormone serotonin, which inhibits brown fat activity, slowing down one's metabolism as they age.
"Too much of this serotonin acts like the parking brake on your brown fat,” Steinberg explained. “You can step on the gas of the brown fat, but it doesn’t go anywhere.”
By inhibiting the production of serotonin, Steinberg says they have released that "parking brake" on the brown fat. The implications, Steinberg said, could be both in reversing obesity, but also preventing diabetes by burning sugar in brown fat so the body does not have to produce insulin in the pancreas to regulate blood sugar.
"We're talking about intervening in the pre-diabetes stage or the early stages of diabetes to try and treat it," Steinberg said.
The discovery came as a result of a collaboration between Steinberg and co-author Waliul Khan, an associate professor of pathology and molecular medicine for the medical school.
Khan, working on the floor below Steinberg, noticed mice with mutations to tryptophan hydroxylase (Tph1), which is the body's main producer of serotonin, were lighter. The two collaborated to see why these mice, which they found did not produce serotonin to slow down brown fat, were less obese and resistant to fatty-liver diseases.
Researchers hope to reverse obesity, prevent diabetes
"When you feed an animal a high fat diet, what you get is more serotonin being produced," Steinberg said. "So what we discovered is that if we remove this enzyme either genetically or if we inhibit its activity using a chemical, a drug, the mice have low levels of serotonin and they didn't develop diabetes, obesity or fatty liver disease."
'"We're just restoring a system that's in place when you're young and healthy.' - Gregory Steinberg, McMaster professor of medicine
"Because (brown fat) is able to use so much sugar, turning it on again could be an important way to increase your basal metabolic rate and lower your blood sugar if you've got diabetes."
Steinberg also noted that the serotonin found in the brain is not linked to what's happening in the digestive tract serotonin. He said it's strictly reflective of "periphery serotonin," and that the serotonin found in the brain, some five per cent of total serotonin in the body, does not interact. The two pools of the same hormone are separated by what's called a blood brain barrier, and do not mix.
It leaves the question of the link between depression, serotonin levels and obesity up in the air, something Steinberg says he can't answer just yet.
He also said they're unsure where the serotonin is being produced in the body to slow down brown fat, and if it is local or body-wide concentrations that matter. Those are the next steps in their research, but says their findings are different from other ways at increasing metabolic rate because it does so with a "good safety profile" of no increases of heart rate and blood pressure in mice.
"We're just restoring a system that's in place when you're young and healthy," Steinberg said.