How the liver proactively prepares for food

Electron micrograph of mitochondria in liver cells

The mitochondria in the liver change shape as soon as food is perceived in the brain. The image shows an electron micrograph of the mitochondria in liver cells. © S. Henscke/ Max Planck Institute for Metabolism Research

When we are hungry and see or smell food, certain nerve cells in the brain are first activated. They signal to the body: food is in sight! Just a few minutes later, the mitochondria in the liver cells change, as a research team has now shown in mice. This causes the liver to prepare for the necessary adjustment of its sugar metabolism even before we have eaten anything, the team reports in “Science”. The results could open up new avenues for treating diabetes.

In order to be able to process the nutrients and energy from food as quickly and efficiently as possible, our body prepares itself before consumption. “When our senses perceive food, our body prepares itself for food intake by producing saliva and stomach acid,” explains Sinika Henschke from the Max Planck Institute for Metabolism Research in Cologne. It is also known from previous studies that the liver also prepares itself for food intake. But how exactly this adapts has so far been unclear.

Adjustment of sugar metabolism begins in the brain

A team led by Henschke has now taken a closer look at the mitochondria in the liver cells. These organelles are responsible for metabolism and energy production in all cells. The researchers therefore suspected that changes in relation to upcoming food are most likely to be found in liver cells. To test this theory, Henschke and her colleagues fed hungry mice. However, the animals were not allowed to eat the food, but were only allowed to see and smell it through a grid for a maximum of 30 minutes. The researchers then examined the mitochondria in the liver cells of the mice using microscopic and molecular biological methods.

They found that the same processes in sugar and fat metabolism that were stimulated in a control group during food intake were activated in the organelles within just five minutes. The team concludes that the fact that the mice had the prospect of food was enough to change the mitochondria in the liver cells. The mitochondria split and fragmented to remodel their metabolic processes. As a result, increased glucose and fatty acids as well as the hormones insulin, glucagon and corticosterone, which regulate sugar and fat metabolism, were found in the animals’ blood, as the analyzes showed. “This adaptation is happening surprisingly quickly,” says Henschke.

Through follow-up tests, she and her colleagues also demonstrated that this effect was previously triggered by a group of nerve cells in the brain, the so-called POMC neurons in the hypothalamus. In the tests, the researchers activated these neurons using light stimuli. The neurons can also be activated within seconds by the smell or sight of food, as is known from previous studies. In both cases, the nerve cells then signal the liver to prepare for the upcoming nutrients, as the team found.

Altered mitochondria affect response to insulin

But what exactly causes the mitochondria in the liver to change? A protein in the mitochondria that is phosphorylated as a result of the nerve signal appears to play an important role – a phosphate group is attached to it by an enzyme. This changes the activity of the protein, the so-called mitochondrial fission factor, and the mitochondria restructure, as the team explains. The experiments also revealed that due to this phosphorylation, the liver reacts somewhat weaker to insulin overall and converts and digests sugar more slowly. The researchers have thus discovered a new signaling pathway that regulates insulin sensitivity in the body.

“Our study shows how closely the sensory perception of food, adaptive processes in mitochondria and insulin sensitivity are linked,” says senior author Jens Brüning from the Max Planck Institute for Metabolism Research in Cologne. “Understanding these mechanisms is also important because insulin sensitivity is impaired in type 2 diabetes mellitus.” The findings could therefore be relevant in the future for the treatment of the widespread disease diabetes. However, for appropriate therapies, follow-up studies must first further research the connections.

Source: Sinika Henschke (Max Planck Institute for Metabolism Research) et al., Science, doi: 10.1126/science.adk1005

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