Study explains why gastric bariatric surgery alters sweet tooth

Procedure affects brain and reduces release of neurotransmitter associated with pleasure and reward, according to researchers' findings.

By Elton Alisson  |  Agência FAPESP – Specialists have known for some time that some kinds of bariatric (weight-loss) surgery, such as gastric bypass, can cause a reduction in craving for sugar. Now, a study performed by researchers at Yale University in the United States, in collaboration with colleagues from other institutions in the US, China and Brazil, has found that this type of bariatric surgery may diminish sweet tooth by inhibiting the brain’s release of dopamine, the hormone associated with pleasure and positive feedback.

Gastric bypass is performed to treat morbid obesity and diabetes. The surgeon staples off a large section of the stomach, leaving a tiny pouch that is then connected to the small intestine.

The study is described in an article in the journal Cell Metabolism and in a Research Highlight in Nature. One of its authors, Tatiana Lima Ferreira, is a researcher at the Federal University of the ABC’s Center for Mathematics, Computation & Cognition (CMCC-UFABC) in São Paulo, Brazil.

Ferreira was awarded a scholarship abroad by FAPESP to do research at Yale University in a laboratory headed by Brazilian researcher Ivan Eid Tavares de Araújo, who coordinated the study.

“Gastric bypass and other kinds of bariatric surgery were already known to cause loss of appetite for sweet food, but the mechanism behind this phenomenon was not understood,” Ferreira told Agência FAPESP. “The study explores how the brain and stomach interact in patients submitted to bypass surgery.”

To find out to what extent chronic sugar consumption may be habit forming or lead to addiction, the researchers performed an experiment consisting initially of exposing a group of mice to set amounts of sugar, which the animals themselves administered by licking the nipple of a bottle containing sugary liquid, for 13 days.

In a second experiment, designed to determine whether chronic sugar consumption led the same mice to crave more sugar even after reaching satiety, the researchers injected sugar directly into the animals’ stomachs in quantities equivalent to the amount that the mice had self-administered in the first experiment and again exposed the mice to the sugar bottle.

The animals evidently continued to crave sugar, as they again spent a long time licking the spout of the sugar bottle.

“The experiment showed that chronic administration of sugar was habit forming in the case of these mice, in contrast with another group of mice exposed chronically to sweetener,” Ferreira said, referring to a third experiment performed by the group.

The researchers then focused on what happened in the brains of the mice that self-administered sugar. Their analysis suggested that a specific brain region called the dorsal striatum released more dopamine while the animals consumed sugar.

“We observed that the brain circuits involved in sugar craving were very similar to those associated with drug addiction,” Ferreira said.

The next step was to find out whether mice chronically exposed to sugar would display a craving for sugar after being submitted to a procedure similar to gastric bypass surgery.

In an operation similar to the Roux-en-Y bypass intervention performed on humans, the animals’ stomachs were directly connected to the jejunum, a part of the small intestine between the duodenum and the ileum. The researchers found that this gastrointestinal rerouting suppressed the animals’ sweet tooth by reducing sugar-induced dopamine release in the dorsal striatum, Ferreira explained.

“Despite having been chronically exposed to sugar, after gastric bypass surgery, the mice no longer craved sugar because of a reduction in the release of dopamine by the dorsal striatum,” she said.

“It’s likely that sweet tooth isn’t associated with sweetness itself, but with the calories supplied by the sugar.”

Habit reactivation

The finding that gastric bypass surgery may diminish sugar craving by reducing striatal dopamine signaling motivated the researchers to perform another experiment, in which they stimulated the dopamine receptors of mice that had been submitted to the operation and observed that the habit of consuming sugar was reactivated.

Using optogenetics, an advanced neuroscience technique whereby genetically encoded light-activated proteins are expressed in a specific brain region via injection of a modified virus, the researchers were able to activate the neural circuits that express dopamine receptors in the animals’ brains.

The result was a striking increase in sugar consumption, overturning the effects of bypass surgery.

“Simply by activating the dopamine pathway in the dorsal striatum, we succeeded in inducing sugar appetite, even in the mice that had had gastric bypass surgery and that previously had consumed only sweetener,” Ferreira said.

The researchers also found that impairment of dopamine-responsive striatal circuits in the mice eliminated sugar craving.

The article “Striatal dopamine links gastrointestinal rerouting to altered sweet appetite” (doi: 10.1016/j.cmet.2015.10.009), by Ferreira et al., can be read by subscribers to Cell Metabolism at www.sciencedirect.com/science/article/pii/S1550413115005252.