How fat signals us to eat more

Overview

Scientists have discovered how fat triggers a gut-to-brain mechanism to keep you consuming more fat. can lead to intervention.

Short ribs glazed in a sweet gooey sauce and slow cooked to perfection, hand-fried crisps drizzled with sour cream, battered and double-fried chicken wings that stay crispy for hours. stay. What makes us reach out and come back for more about these mouth-watering yet incredibly fatty foods?

How they taste on the tongue is part of the story, but to really understand what drives “our insatiable appetite for fat,” what happens after the fat is consumed? need to be investigated, say researchers at Columbia University. charles zukerNeuroscientist and molecular geneticist, Howard Hughes Medical Institute (HHMI) investigator since 1989.

Two years ago, Zuker and his team report How, once sugar reaches the gut, it triggers signals sent to the brain, stimulating cravings for sweet treats. Nature Sept. 7, 2022, they describe a similar gut-to-brain circuit that underlies our preference for fat.

“The gut is the source of our great appetite for fat and sugar,” says Zuker.

Given the current global obesity epidemic, the topic in question is an incredibly timely one. 13% of adults worldwide are obese — three times more than in 1975. In the United States, the numbers are even higher — Amazing 42%“This is a very serious and important health issue,” says Zuker.

A high body mass index is a risk factor for stroke, diabetes, and several other diseases. “It’s clear that if we want to help make a difference here, we need to understand the biological underpinnings of our cravings for fat and sugar,” he says. We can help curb this strong consumer appetite and design interventions to combat obesity.

To figure out why we like fat, Mengtong Li, a postdoctoral researcher in the Zuker lab at Columbia University, conducted a series of experiments in mice. From various previous studies, researchers believed that this preference occurred after ingestion, similar to that of sugar.

“The gut is the source of our great appetite for fat and sugar.”

Charles Zuker, HHMI investigator at Columbia University

To test their hypothesis, they provided the animals with two bottles: one containing artificial sweeteners and one containing fat. but the latter was clearly the favourite, after 48 hours. Because artificial sweeteners only send signals to the brain when they hit the tongue and not after they’ve been swallowed, a behavioral switch in mice proved the researchers’ hunch correct. It drives the gut and thus our desire for it.

This behavioral assay was an important first step in the study, says Li. “Because we can begin to dissect where the fat-sensing circuits are and look at their effects on both physiology and behavior.”

The circuit runs from the gut to the brain, as revealed by further experiments using knockout mice and various molecular-specific inhibitors. The team found that fat sensing occurs through a series of steps. When fat enters the intestine, it binds to special receptors. This in turn sends signals to neurons through the gut-brain axis, activating neurons in the brainstem. As a result, the rest of the brain receives the message. It means that the fat is consumed and you feel better.

Interestingly, the team identified two parallel gut-to-brain signaling pathways. One is triggered only by intestinal fat, and the other is the more general pathway activated by any of the three essential nutrients: fats, sugars, or amino acids. It uses the hormone cholecystokinin (CCK) as the substance.

“The underlying biology behind the fat preferences they uncovered is really interesting,” says the molecular neurobiologist. Steven Liberless HHMI researcher at Harvard University who was not part of the new paper. Unlike external sensory systems such as touch, taste, and smell, interoception—the way the body receives information from internal organs—is poorly understood, he says. “So, elucidating receptors for ingested fat is a very exciting advance.”

Zuker’s group is now studying what happens when fat-induced signals reach the brainstem. “It needs to be sent to the rest of the brain to ultimately activate the circuitry that motivates you to continue consuming fat,” says Zuker.

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Quote

Mengtong Li et al. “Gut-brain circuitry for fat preference”. NaturePublished online September 7, 2022. doi: 0.1038/s41586-022-05266-z