For example, researchers have now found that bile acids have a role in signalling. These fluids help to emulsify fats so that the lipids are metabolized more efficiently, but they also act as hormones, signalling to receptors in the gut. Randy Seeley, a neuroscientist at the University of Michigan Health System in Ann Arbor, and his colleagues decided to look at what happens when one of these bile-activated-receptors — the farsenoid-X receptor (FXR), which helps to regulate glucose metabolism — is deleted in mice.
The researchers overfed both mutant and control mice until they were fat, and then did a vertical sleeve gastrectomy. (This procedure shrinks the stomach like a gastric bypass does, but does not circumvent any of the small intestine.) A week after surgery, both types of mice lost a lot of weight. By the fifth week, however, only the control mice had managed to keep it off; the mutants had gained it all back11. Without FXR and the messages carried by bile acids, the surgery fails to work.
Intriguingly, the control mice, but not the mutants, showed a notable increase in the abundance of Roseburia, a Firmicutes bacterium that tends to be suppressed in people with diabetes, suggesting that FXR and its related biological pathways could turn out to be therapeutic targets in this disease.
Bile-acid and bacterial changes could affect the gut's communication with organs responsible for the glucose dysregulation that causes diabetes. But a study published last year12 suggests that the gut itself shows changes in glucose metabolism after surgery (see Nature http://doi.org/tjr; 2013).
Using a rat model of gastric bypass, Stylopoulos, who now runs his own laboratory at Boston Children's Hospital, and his colleagues showed that the 'Roux limb' — the piece of intestine that runs from the stomach pouch to the reconnected intestine — expands dramatically in width and length after surgery. “It really doubles in size,” Stylopoulos says, and it stays that way. That makes sense, because without a full-sized stomach, the tissue must adapt to heaps of undigested food. But the limb's rapid growth requires a lot of energy, which comes from glucose. The changing organ starts to use more glucose, and the change is maintained over time, Stylopoulos says. “Essentially, the intestine becomes a bigger and a more hungry organ that needs more glucose than before.”
Stylopoulos believes that this tissue growth in the gut is the main driver of the surgery's remarkable metabolic benefits — not the reduction in calorie intake. “Surgery works because it changes the physiology,” he says.
Weight loss is still important, however, because it triggers a series of changes that help to curb diabetes.
For example, researchers have now found that bile acids have a role in signalling. These fluids help to emulsify fats so that the lipids are metabolized more efficiently, but they also act as hormones, signalling to receptors in the gut. Randy Seeley, a neuroscientist at the University of Michigan Health System in Ann Arbor, and his colleagues decided to look at what happens when one of these bile-activated-receptors — the farsenoid-X receptor (FXR), which helps to regulate glucose metabolism — is deleted in mice.
The researchers overfed both mutant and control mice until they were fat, and then did a vertical sleeve gastrectomy. (This procedure shrinks the stomach like a gastric bypass does, but does not circumvent any of the small intestine.) A week after surgery, both types of mice lost a lot of weight. By the fifth week, however, only the control mice had managed to keep it off; the mutants had gained it all back11. Without FXR and the messages carried by bile acids, the surgery fails to work.
Intriguingly, the control mice, but not the mutants, showed a notable increase in the abundance of Roseburia, a Firmicutes bacterium that tends to be suppressed in people with diabetes, suggesting that FXR and its related biological pathways could turn out to be therapeutic targets in this disease.
Bile-acid and bacterial changes could affect the gut's communication with organs responsible for the glucose dysregulation that causes diabetes. But a study published last year12 suggests that the gut itself shows changes in glucose metabolism after surgery (see Nature http://doi.org/tjr; 2013).
Using a rat model of gastric bypass, Stylopoulos, who now runs his own laboratory at Boston Children's Hospital, and his colleagues showed that the 'Roux limb' — the piece of intestine that runs from the stomach pouch to the reconnected intestine — expands dramatically in width and length after surgery. “It really doubles in size,” Stylopoulos says, and it stays that way. That makes sense, because without a full-sized stomach, the tissue must adapt to heaps of undigested food. But the limb's rapid growth requires a lot of energy, which comes from glucose. The changing organ starts to use more glucose, and the change is maintained over time, Stylopoulos says. “Essentially, the intestine becomes a bigger and a more hungry organ that needs more glucose than before.”
Stylopoulos believes that this tissue growth in the gut is the main driver of the surgery's remarkable metabolic benefits — not the reduction in calorie intake. “Surgery works because it changes the physiology,” he says.
Weight loss is still important, however, because it triggers a series of changes that help to curb diabetes.
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