‘You are what you eat’ is an old saying from the Greeks but it might be more accurate to say ‘You are what your gut microflora and fauna eat’ and certainly how fat you may become. Yale based researchers have identified a possible mechanism for obesity in a study on rats which is linked to their gut’s microbes. The research was published in Nature and news of the discovery posted on the Yale web-site. The lead researcher, Gerald I. Shulman who is the George R Cowgill Professor of Medicine at Yale University and co-Director at the Yale Diabetes Research Center had noticed from an earlier observation that the short chain fatty acid, acetate, produced as an end product of fat metabolism, stimulated the secretion of insulin in mice. This research was continued into obesity by using rats for modelling fat metabolism at Yale and the Howard Hughes Medical Institute with input from the Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen 2200, Denmark.

The research team compared acetate to other short-chain fatty acids and found higher concentrations of this metabolite 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 this might be occurring.

The researchers then found that acetate which was injected directly into the brain, triggered increased insulin production by activating the parasympathetic nervous system.

“Acetate stimulates beta cells to secrete more insulin in response to glucose through a centrally mediated mechanism,” stated Shulman. “It also stimulates secretion of the hormones gastrin and ghrelin, which leads to increased food intake.”

In the course of these studies, the researchers attempted to uncover a causal relationship between the gut microbiota and increased insulin production. They transferred faecal matter from one group of rodents to another whereupon they saw similar changes to 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. Increasing acetate levels leads to increased food intake which is part of a positive feedback loop that promotes fat deposition along with insulin resistance. Such features are part of a developing trend in metabolic syndromes. The researchers are keen to find out if this mechanism operates in humans.

The authors postulate that this positive feedback loop has an important role in evolution, by prompting animals to fatten up when they stumbled across calorifically dense food at times of food scarcity.

Reference

Nature 534, pp. 213–217 (09 June 2016) doi:10.1038/nature18309