According to a new study performed in zebrafish (Danio rerio), a high-fat meal can shut down the communication between the enteroendocrine cells — specialized sensory cells in the intestinal epithelium that sense and transduce nutrient information — and the rest of the body for a few hours.
An enteroendocrine cell (green) lies within the epithelium (red) that lines the intestines of a zebrafish larvae. Image credit: Lihua Ye.
Enteroendocrine cells are dispersed along the entire gastrointestinal tract but comprise only about 1% of gut epithelial cells. However, collectively these cells constitute the largest, most complex endocrine network in the body.
They synthesize and secrete hormones in response to ingested nutrients including carbohydrates, fatty acids, peptides and amino acids. They also have a direct connection to the nervous system and the brain.
“But they fall asleep on the job for a few hours after a high-fat meal, and we don’t yet know if that’s good or bad,” said Dr. John Rawls, a researcher in the Department of Molecular Genetics and Microbiology at the Duke University School of Medicine.
To understand the silencing better, the team tried to break the process down step by step in zebrafish.
After they first sense a meal, the enteroendocrine cells trigger a calcium burst within seconds, initiating the signaling process.
“But after that initial signal there’s a delayed effect later in the after-meal period. It’s during this later response that the silencing occurs,” Dr. Rawls said.
The silenced cells change shape and experience stress in their endoplasmic reticulum, a structure that assembles new proteins. It seems that these cells become overstimulated and exhausted for a while.
The scientists fed a high-fat diet to a line of germ-free zebrafish, and found the fish didn’t experience the same silencing effect. So they began looking for gut microbes that might be involved in the process.
After screening through all the kinds of bacteria found in the gut, they saw that the silencing appeared to be the work of Acinetobacter.
These gut bacteria are normally less than 0.1% of the total gut microbiome, but they increased 100-fold after a high-fat meal and were the only bacteria able to induce the silencing effect.
“Next we want to understand how Acinetobacter evokes this interesting response. We also suspect other bacteria might also have this capability,” said Dr. Lihua Ye, a postdoctoral researcher in the Department of Molecular Genetics and Microbiology at the Duke University School of Medicine.
“We don’t understand yet what the long-term impact of enteroendocrine silencing would be on metabolic health,” Dr. Rawls said.
“This may be a maladaptive response to high-fat feeding that impairs the normal regulatory functions of these cells, leading to metabolic disorders like insulin resistance. But it’s also possible that the silencing is a beneficial adaptation to protect the animal from over-stimulation of the gut cells.”
The findings appear online in the journal eLife.
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Lihua Ye et al. 2019. High fat diet induces microbiota-dependent silencing of enteroendocrine cells. eLife 8: e48479; doi: 10.7554/eLife.48479
