How blocking an enzyme involved in protein digestion could improve metabolic health

An image of human cells to illustrate metabolic health

Blocking an enzyme involved in protein digestion could improve metabolic health, according to a new study.

The study is titled “Intestinal serine protease inhibition increases FGF21 and improves metabolism in obese mice” and is published in the American Physiological Society. It describes how blocking trypsin, the primary enzyme for digesting protein in the digestive tract, may improve metabolic health in rats.

The drugs that block the protein digestion by trypsin are called serine protease inhibitors. In rats, the study found that they:

  • Reduce weight gain;
  • High blood sugar; and
  • High cholesterol.

However, the process in which serine protease inhibitors improve metabolic health is not well understood.

Improving the metabolic health of mice

On overweight mice, the researchers found that one week of treatment with serine protease inhibitors reduced the amount of food they ate and led to weight loss, better blood sugar levels, and improved liver function, compared to animals that were just given the same reduced amount of food. This suggests that other factors as well as caloric restriction contributed to the improved metabolic health.

Bloodwork performed on the mice before and after the experiment showed that the level of the hormone fibroblast growth factor 21 (FGF21), which suppresses appetite and manages metabolism, weight loss and glucose, was higher during treatment.

Additionally the study also found that drug treatment activated a signalling pathway called the integrated stress response (ISR), which also caused FGF21 levels to rise.

The integrated stress response can be triggered by a number of physiological stresses. These include protein deprivation and amino acid deprivation.

Although the protein in the mice’s diets was not restricted, the camostat tricked the mice’s bodies into thinking it was. This activated the ISR.

The importance of trypsin

The researchers concluded: “Trypsin inhibition could be a way to enhance [FGF21 production], resulting in beneficial effects.”

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