Acetic acid and its alter ego, acetate, are part of a group of molecules known as short chain fatty acids (SCFAs). When the team tested other molecules in this group, they found that propionate, which is similar to acetate, also binds Olfr78. In the body of mammals, including humans, SCFAs are made when zillions of bacteria lining the gut digest starch and cellulose from plant-based foods. The SCFAs are absorbed by the intestines into the blood stream, where they can interact with Olfr78.
To pinpoint the effect of Olfr78, the scientists gave SCFAs to mice missing the Olfr78 gene and found that the rodents' blood pressure decreased, suggesting that SCFAs normally induce Olfr78 to elevate blood pressure. However, when they gave SCFAs to normal mice with intact Olfr78, they did not see the expected increase in blood pressure, but rather a decrease, though it was less pronounced than before.
To test the effect of reducing the SCFAs available to Olfr78, the team gave mice a three-week course of antibiotics to wipe out the gut microbes responsible for SCFA production. In this case, normal mice showed very little change in blood pressure, but mice without Olfr78 experienced an increase in blood pressure, suggesting that there were other factors involved in the Olfr78/SCFA/blood pressure relationship.
The mystery was solved, Pluznick says, when the team examined mice lacking Gpr41, a non-smell-related protein receptor located in blood vessel walls that also binds SCFAs. When SCFAs bind to Gpr41, blood pressure is decreased. The researchers eventually discovered that Olfr78 and Gpr41 both are activated by SCFAs, but with contradictory effects. The negative effect of Gpr41 is counterbalanced by the positive effect of Olfr78, but Gpr41's effect is stronger, so an increase in SCFAs produces an overall decrease in blood pressure.
|Contact: Catherine Kolf|
Johns Hopkins Medicine