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Weight-Loss Surgery: It's Not Just About Stomach Size
Published: Mar 26, 2014 By Elizabeth DeVita Raeburn, Contributing Writer, MedPage Today
The study focused on the fact that "substantial changes in circulating total bile acids are known to occur after VSG," and the fact that these bile acids are known to regulate metabolism by binding to the nuclear FXR receptor (farnesoid-X receptor), said Randy J. Seeley, PhD, of the University of Cincinnati, and colleagues in Nature.
"We hypothesized that FXR-signaling links altered bile-acids homeostasis to important postoperative changes in metabolism and gut microbial communities, thereby contributing to the maintenance of weight loss and improvements in glucose control" following VSG, they said.
Bariatric surgery is often the most "effective and durable" therapy for obesity, the authors wrote, adding that 40% of obese type-2 diabetes mellitus patients who undergo bariatric surgery achieve full remission within a year.
The presumption has been that the weight loss is due to smaller stomach size imposed by the surgery, but a growing body of evidence suggests that changes in gut physiology after the surgery also exert an important effect, the authors said.
"As just one example, a substantial proportion of diabetic patients are able to stop taking their medications within days of surgery, before substantial weight loss has occurred," they wrote.
In a series of experiments, the researchers also performed VSG, in which approximately 80% of the stomach is removed, on mice with diet-induced obesity, some of which were knockout (KO) FXR mice.
In the first week, both wild-type (WT) and KO mice that had undergone VSG lost weight compared with sham-operated controls. But while the wild-type mice sustained the weight loss, the KO mice did not, the researchers said.
"Within 5 weeks, the body weight of KO-VSG animals was no longer different from that of sham-operated controls," they said.
Eleven weeks after the surgery, "WT-VSG animals had half the body fat of sham-operated WT controls, while the body fat of KO-VSG and KO-sham operated mice was equivalent," the researchers said.
Observation of feeding behavior after the surgery revealed that, while KO-VSG mice initially reduced food intake in the week after surgery, they soon increased it.
Four weeks after surgery, the KO-VSG mice consumed more food than sham operated controls "suggesting that FXR signaling is necessary for the repression of rebound hyperphagia following caloric restriction initially achieved by VSG," the authors said.
When the researchers challenged the glucose tolerance of the mice with an intraperitoneal injection of dextrose, they found that WT-VSG mice "exhibited a substantial improvement" in their ability to clear the glucose, while KO-VSG and sham-operated mice showed no differences in glucose tolerance.
Investigation of the mice's gut microbiota also revealed that VSG had a stronger effect on microbiota composition in WT mice than KO mice, the researchers said.
The relative abundance of Bacteroides, for instance, was substantially reduced in WT-VSG mice relative to WT-sham controls, but did not vary with surgery among KO mice.
A recent study of probiotic treatment of obese women found decreasing numbers of Bacteroides to be associated with less fat and better glucose control. That association was also evident in this study.
"Taken together, the present results demonstrate that a functional FXR pathway is necessary for sustained weight loss, suppression of rebound hyperphagia, and improved glucose control following VSG," the authors wrote.
The findings provide a new understanding of the mechanisms underlying the success of bariatric surgery and suggest new targets for less invasive therapeutic interventions, they said.