UNIGE study links vegan diet to rapid liver metabolic shifts

Metabolic changes occur within days when mice switch from a mixed protein diet to one exclusively plant-based, according to new research from the University of Geneva (UNIGE). The study identifies glutamate dehydrogenase (GDH), a liver enzyme, as central to these shifts. Published in Molecular Metabolism, the findings reveal that such dietary modifications significantly reduce the animals' willingness to engage in physical exercise.

How GDH affects metabolism

In Switzerland, tens of thousands of people adhere to vegan diets, which exclude all animal-derived products. While plant-based eating is often recommended for environmental reasons, its health impacts remain incompletely understood. UNIGE scientists investigated this by comparing two groups of mice: one fed a lacto-vegetarian diet containing both animal and plant proteins, and another on a strict vegan regimen.

Pierre Maechler, a full professor at the Department of Cell Physiology and Metabolism and the Diabetes Centre of the UNIGE Faculty of Medicine, led the investigation. His team focused on how amino acids—the building blocks of proteins—vary between sources. Plant-based proteins naturally contain fewer branched-chain amino acids than their animal counterparts. These specific amino acids provide the liver with raw material necessary to produce and maintain blood glucose levels during fasting periods.

Rapid physiological responses observed

Within just two days, mice on the exclusively vegan diet exhibited less efficient glucose production. Their livers also struggled more with eliminating ammonia, a toxic substance released during amino acid breakdown. A significant reduction in physical activity suggested broader effects on the body’s overall function.

The impaired regulation of glucose and ammonia pointed to the involvement of GDH. Located in the mitochondria of liver cells, this enzyme acts as a bridge between protein and sugar metabolism. To confirm its role, researchers compared two additional groups of mice lacking GDH in the liver, one on a lacto-vegetarian diet and the other on a vegan diet.

In mice fed only plant proteins, the absence of GDH caused severe ammonia buildup and disrupted blood glucose regulation compared to those receiving animal proteins. This confirmed the enzyme's essential role in the metabolic changes induced by a strict vegan diet.

Dietary reversibility and balance

"Overall, a change in diet alters liver metabolism very quickly, but this effect is just as rapidly reversible," emphasized Pierre Maechler. He noted that the body adapts within one to two days to subtle changes in dietary composition. Normal function returns upon the reintroduction of animal proteins.

This adaptability highlights the liver's remarkable plasticity but carries practical implications for everyday nutrition. Beyond ethical and environmental motivations for switching to veganism, the study suggests that diversifying the diet helps maintain metabolic balance.