In recent years, gastric bypass surgery has increased in popularity and remains one of the few methods for the treatment of obesity. While there are several different procedures that can be done to resection the gut, all techniques are based on one of two basic premises: reducing the size of the stomach and/or skipping portions of the small intestine in order to reduce the ability of the gut to absorb nutrients. The success of these procedures is largely due to the resulting reduction in calorie intake. This is, in part, related to the decrease in the physical size of the stomach, but when portions of the small intestine are bypassed, there is also a decrease in sweet appetite. The mechanism behind this phenomenon, however, is largely unknown.
A recent study published in Cell Metabolism by Han et al. utilized a mouse model to illustrate some very interesting connections between the upper portion of the small intestine, the duodenum, and the animal’s drive to consume sweets. While not always directly applicable to human physiology, mouse models are an essential step in bridging the gap between in vitro studies working at the microscopic, cellular level and clinical trials involving human subjects. A hypothesis must show scientific potential and safety in a living, higher-level organism, commonly a mouse, before it can be tested in humans.
The researchers hypothesized that the duodenum would be able to sense sugar and would subsequently signal the brain to release dopamine. Increased dopamine is known to enhance our appetite for sweetness. Two types of mice were used. Some had complete, unaltered intestines, known as sham mice, and others had undergone a duodenal-jejunal bypass (DJB) intervention. In these DJB mice, the stomach was rerouted to empty into a lower portion of the small intestine, the jejunum, instead of into the duodenum.
Left: Signaling pathway from gut to brain in sham mice
Right: Signaling pathway from gut to brain in DJB mice
Researchers found that sham mice that regularly ate sugar, as apposed to a low-calorie sweetener, had a much greater appetite for sweetness. The DJB mice that ate sugar, however, did not have the same increased sweet tooth. This supports the idea that something different is happening when sugar passes through the duodenum specifically. There is some signaling pattern to the brain that is missed when the duodenum is bypassed.
To get a clearer picture, researchers looked directly at the brain. They injected sugar straight into the duodenums of both sham and DJB mice. The sham mice experienced a significantly greater release of dopamine compared to the DJB mice. To be sure that it was specifically the duodenum that was causing this response, they also injected sugar into the jejunum and jugular vein. Still, the duodenal infusions resulted in a much greater release of dopamine.
Looking forward, these results may be used to inform future interventions in humans. As mentioned previously, mouse models are important for indicating what experiments should be pursued further. We cannot say for certain if the results seen so profoundly in these experiments will translate fully when applied to real, free living humans. Is the signaling between the gut and the brain as potent in a more complex organism? It is not likely that a person will consume a meal of sugar alone. What happens to this relationship when other components, like fat, protein, or fiber, are included in the meal? Future research should aim to answer these questions and better define how this new information can be used to support people who have undergone gastric bypass.
Source:
Han, W., Tellez, L.A., Niu, J., Medina, S., Ferreira, T. L., Zhang, X., ... & De Araujo, I. E., (2016). Striatal dopamine links gastrointestinal rerouting to altered sweet appetite. Cell Metabolism, 23(1), 103-112.