While investigating a protein whose production is known to be elevated in a wide range of cancers, a team of researchers has inadvertently discovered a powerful new metabolic regulator that in early mouse experiments has reduced the animal's fat levels by a third.
Fibroblast growth factors (FGFs) are fundamentally important proteins that are found in a wide variety of organisms, including mammals. Three members of the FGF family, known as BP1, BP2 and BP3, are euphemistically referred to as "chaperone" proteins because they bind to primary FGF proteins, enhancing their activity.
Anton Wellstein, from Georgetown University and a senior investigator on the new research, has been examining BP1 for many years as it has been found in elevated levels in patients with a variety of cancers. It has been hypothesized that an over expression of BP1 may potentiate the biological effects of FGFs, increasing the proliferation of cancer cells.
Recently, Wellstein and his team began investigating the effects of BP3 and discovered that it binds to three specific FGF proteins, all known to regulate metabolic activities. Two proteins in particular, FGF19 and FGF21, regulate how a body both uses, and stores, sugar and fats.
"We found that BP3 exerts a striking contribution to metabolic control," explains Wellstein. "When you have more BP3 chaperone available, FGF19 and FGF21 effect is increased through the increase of their signaling. That makes BP3 a strong driver of carbohydrate and lipid metabolism. It's like having a lot more taxis available in New York City to pick up all the people who need a ride."
Wellstein suggests that excess levels of BP3 can essentially amp up a body's metabolism, forcing sugar and fat that is processed in the liver to be used for energy, and not stored. To test out this hypothesis the researchers evaluated the effects of altered BP3 levels in several different mouse models.
First, a mouse model was engineered to produce no BP3 whatsoever. These mice subsequently displayed abnormal glucose tolerance and lowered levels of circulating triglycerides, suggesting the animals were suffering from notably dysfunctional metabolism.
The researchers then examined what would happen if mice, engineered to be obese, were administered excess levels of BP3. Excitingly, the animals responded extraordinarily positively, with reduced hypoglycemic symptoms and a reduction in liver fat. On top of this, the animals' overall fat levels dropped by more than 30 percent.
"We found that eight BP3 treatments over 18 days was enough to reduce the fat in obese mice by over a third," says Wellstein.
Further preclinical studies are still necessary before the researchers can move on to examine BP3's effects in human trials, but the research is an excitingly positive discovery uncovering the striking potential in this natural protein.
The study was published in the journal Scientific Reports.
Source: Georgetown University
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