Low-Protein Diet Shrunk the Livers of Mice, But Changes Were Reversible

Magdalena Kegel, PhD avatar

by Magdalena Kegel, PhD |

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illustration of liver and a DNA strand

A diet too low in protein causes the liver to shrink extensively and become less efficient in doing its work. That can have devastating effects on nerve signaling and movement, as well as prevent the body from properly metabolizing medications.

But the findings in a recent study using mice also showed this damage is reversible, offering hope to people who have been malnourished for a longer time.

The study, “Stereology shows that damaged liver recovers after protein refeeding,” was published in the journal Nutrition.

“It is important not to underestimate the importance of protein in our diet,” senior author Augusto Coppi, BVSc, PhD, at the University of Surrey in the U.K., said in a press release. “From building and repairing tissues, to making enzymes and hormones, protein is a vital component of our bodies’ functionality.”

Researchers long have known that malnutrition impacts the liver. But to get a better idea of how particularly low levels of protein impact the liver and its cells, the Surrey researchers, along with colleagues at the University of São Paulo in Brazil, fed mice a low-protein diet for five weeks.

To bring additional value to the study, they used a new method, called design-based stereology, that can estimate the volume of the liver along with the numbers and sizes of liver cells in a three-dimensional manner.

After only five weeks, the liver volume of the mice had shrunk by 65%. Normal liver cells had been reduced by 46%, while so-called binucleate hepatocytes — liver cells with two nuclei — increased by an astonishing 90%. These changes made the liver work less efficiently.

In addition, the protein albumin, which is secreted by the liver and is the main protein in our blood, was reduced by 20%.

After five weeks, mice were again put on a diet with normal levels of protein. Measuring the liver again five weeks later showed the liver damage had been partially reversed. The liver volume had increased 1.5-fold and the volume of normal liver cells had increased by 85%.

Researchers believe that if they studied the mice for a longer period, they might have observed a total recovery.

“Our research has shown a worrying atrophy of the liver and of its cells, which can affect the whole body metabolism,” said Coppi. “However, on the positive side, what we have also found is that this harm is not permanent, and the liver has an amazing capacity to regenerate itself and return to its normal functionality.”

“This is an encouraging discovery for those having suffered long periods of malnutrition that no permanent damage has been caused,” added Coppi.