How Altered Gut Microbes Cause Obesity

New research from Yale University details how altered gut microbiota causes obesity.
Obesity is linked to changes in our gut microbes — the trillions of tiny organisms that inhabit our intestines.
But the mechanism has not been clear. In a new study published in Nature , a Yale-led team of researchers has identified how an altered gut microbiota causes obesity.
In an earlier study, Dr. Gerald I. Shulman, the George R. Cowgill Professor ofbMedicine, observed that acetate, a short-chain fatty acid, stimulated the secretion of insulin in rodents. To learn more about acetate’s role, Shulman, who is also an investigator of the Howard Hughes Medical Institute, and a team of
Yale researchers conducted a series of experiments in rodent models of obesity.
The research team compared acetate to other short- chain fatty acids and found higher levels of acetate in animals that consumed a high-fat diet. They also observed that infusions of acetate stimulated insulin secretion by beta cells in the pancreas, but it was unclear how.
Next, the researchers determined that when acetate was injected directly into the brain, it triggered increased insulin by activating the parasympathetic nervous system. “Acetate stimulates beta cells to
secrete more insulin in response to glucose through a centrally mediated mechanism,” said Shulman. “It also
stimulates secretion of the hormones gastrin and ghrelin, which lead to increased food intake.”
Finally, the research team sought to establish a causal relationship between the gut microbiota and increased
insulin. After transferring fecal matter from one group of rodents to another, they observed similar changes in the gut microbiota, acetate levels, and insulin.
“Taken together these experiments demonstrate a causal link between alterations in the gut microbiota in
response to changes in the diet and increased acetate production,” said Shulman. The increased acetate in turn leads to increased food intake, setting off a positive feedback loop that drives obesity and insulin resistance, he explained.
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