Tracking down satiety mechanisms in the stomach

Bitter protein fragments stimulate gastric acid secretion

13-Oct-2022 - Germany

Casein makes up the majority of the proteins in cheese and quark. Although casein itself does not taste bitter, its digestion in the stomach also produces bitter-tasting protein fragments (peptides). This has been proven for the first time in a study led by the Leibniz Institute for Food Systems Biology at the Technical University of Munich (LSB). The study also suggests that the bitter peptides are able to stimulate acid secretion from gastric cells via their cellular bitter receptors. A mechanism that, according to the research team, could contribute to the long-known satiating effect of milk protein.

J. Krpelan, LSB

Phil Richter in the lab

Not only the gut, but also the stomach is involved in hormonal hunger-satiety regulation. "We know from our own and other studies, that bitter substances can stimulate gastric acid secretion, increase serotonin release from gastric cells, delay gastric emptying, as well as exert a satiating effect," explains principal investigator Veronika Somoza. "Interestingly, protein building blocks such as the bitter-tasting amino acid L-arginine are also among the bitter substances with a satiety effect," she continues.

This gave Veronika Somoza's team the idea of testing whether casein digestion in the stomach produces peptides that, like L-arginine, can act directly on gastric cells.

Enzymatic digestion releases bitter substances

To do this, the team used pigs as an animal model, since their digestive tract is very similar to that of humans. As the study results show, physiologically relevant amounts of bitter peptides are indeed also produced during the natural casein digestion in the stomach. "We were able to demonstrate this exemplarily for five peptides using state-of-the-art food chemistry analysis methods and with the help of sensory tests," says first author Phil Richter, who holds a doctorate at LSB and contributed significantly to the study.

Further molecular biology studies by the team also demonstrate that three of these peptides are capable of boosting acid secretion from human gastric cells in a cellular assay system. The peptides are six, eight and seventeen amino acids in length. Gene expression analyses of the gastric cells and knock-down experiments also suggest that the peptides exert their effect via two gastric cell-specific bitter receptor types. The latter are also found on the tongue and are relevant there for the taste perception of bitter substances.

Peptides and bitter receptors with regulatory potential

Veronika Somoza, director of the LSB, concludes: "Our results suggest that the bitter peptides released from casein already stimulate regulatory mechanisms in the stomach that are partly responsible for the satiating effect of milk protein. Two bitter receptors are probably also involved in these." According to the Leibniz director, clinical studies are now needed to further test the regulatory potential of such peptides and also that of extraoral bitter receptors. "If our hypothesis is confirmed, it would be conceivable in the future to target non-bitter, palatable proteins for foods from which more bitter but satiating peptides are released in the stomach. These could help regulate food intake and ultimately maintain a healthy body weight," adds Phil Richter.

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