A new study has found that obesity can be caused by changes in our gut microbes and that acetate, a short-chain fatty acid, is responsible for this change.

Gut microbes or gut microbiota, which are the trillions of tiny organisms inhabiting our intestines, have long known to be linked to obesity but the mechanism that brings this about has remained unexplored. Research by a Yale-led team of researchers has now identified how an altered gut microbiota causes obesity.

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Dr. Gerald Shulman, MD, the George R. Cowgill Professor of Medicine at Yale and a team of Yale researchers conducted a series of experiments in rodent models of obesity. In an earlier study, Dr. Shulman observed that acetate, a short-chain fatty acid, stimulated the secretion of insulin in rodents. Dr. Shulman then decided to investigate this probable link.

Acetate is the most common building block for biosynthesis. Fatty acids are produced by connecting the two carbon atoms from acetate to a growing fatty acid.

The team compared acetate to other short-chain fatty acids and found higher levels of acetate in animals that had 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.

Researchers then 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 Dr. 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 Dr. Shulman.

The increased acetate leads to increased food intake, setting off a positive feedback loop that drives obesity and insulin resistance, he explained.

The study authors suggest that this positive feedback loop may have served an important role in evolution, by prompting animals to fatten up when they stumbled across calorically dense food in times of food scarcity.

"Alterations in the gut microbiota are associated with obesity and the metabolic syndrome in both humans and rodents," said Dr. Shulman. "In this study we provide a novel mechanism to explain this biological phenomenon in rodents, and we are now examining whether this mechanism translates to humans."

Tagsobesity, Gut microbes, gut microbiota, Dr. Gerald Shulman