Gene Removal Leads Us One Step Closer to a Diet Pill

When FIH was removed, researchers expected the mice to die as embryos, as the enzyme affects developmental genes. Instead, they acted like they were constantly at high altitudes, but were otherwise more fit than normal.

“We [removed the gene] thinking that the mouse would not survive past early embryogenesis, because we know [FIH is part of] a very important pathway [in controlling response to low oxygen],” biology professor Randall Johnson said. “But it turned out the mouse was born, and was a bit healthier in some ways than a normal mouse. It is leaner and has less fat than a normal mouse.”

Johnson’s lab found that mice without FIH were constantly hyperventilating — trying to increase their respiration to take in more oxygen — leading them to take in 20 to 40 percent more air than normal, while demonstrating a faster heart rate and drinking 30 to 40 percent more water.

Because breathing burns calories, the mice developed faster metabolisms, protecting them from obesity.

The genetically altered mice had high insulin sensitivity, which reduces blood sugar and protects against weight gain induced by high-fat diets, and stayed lean. They were also smaller than the normal mice, since weight gain had been inhibited since birth.

However, the mice without the FIH gene experienced the same side effects that are associated with “altitude sickness,” or the result of moving quickly from low to high altitudes: hyperventilation, higher heart rates and anemia.
Johnson said that a drug could be developed to suppress FIH in order to treat obesity and diabetes for those who cannot exercise.

“There are people who are in such bad shape that they may need some drug to help them [in addition to] eating less and exercising more,” Johnson said. “Of course, changing lifestyles is a very important thing, but some people need immediate help. That’s one of the reasons why these drugs can be useful.”

The lab is investigating whether known chemical compounds that also inhibit FIH have similar effects.

For humans, just triggering the body’s response to low oxygen levels may not prevent diabetes or obesity. The researchers will first have to discover the specific amount of oxygen needed in order to metabolize food.

Readers can contact Regina Ip at [email protected].