Damage to tiny liver protein may cause heart disease

In a first, researchers have identified a tiny liver protein that when disrupted can lead to cardiovascular disease as well as fatty liver disease, a precursor to cancer.
The chief culprit in disabling the protein's delicate mechanics is a fatty acid found in red meat and butter, according to Shadab Siddiqi from University of Central Florida in the US.
Low density lipoproteins (VLDL) by the liver are known to increase cholesterol levels, a risk factor for plaque buildup in the arteries, he said.
For healthy liver function, normal VLDL secretion must be kept in a delicate balance. Too little VLDL secretion causes fatty liver and, potentially, liver cancer, researchers said.

Identifying the protein and what activates it is the first step in finding ways to prevent its malfunction and disease.
Siddiqi discovered a tiny protein - a small Valosin-containing Protein called Interacting Protein (SVIP) - that regulates how much VLDL is secreted into the blood.

SVIP in the liver must be regulated properly to ensure optimum health, said Siddiqi.
He equated the operation of the tiny protein to a manually operated car. To run smoothly, the driver must synchronise the gas pedal and the clutch.
If the two are not synchronised, the car does not move easily; it has fits and starts and ultimately stalls.

After identifying the SVIP protein, researchers found that it contains a binding site for myristic acid, a saturated, 14-carbon fatty acid that occurs in butterfat and animal fats, especially red meat.
Based on that finding, researchers studied the effects of different dietary fats, including myristic acid, on the functioning of SVIP.
They found that only myristic acid activated SVIP to secrete excess very low-density proteins into the blood.
If myristic acid was absent, they found the liver failed to secrete any VLDL. That caused fats to build up in the liver, which can lead to cancer, researchers said.
The findings suggest that high levels of myristic acid in the diet - through animal and dairy fats - keep SVIP from properly regulating the liver's secretion of VLDL, they said.

"These findings suggest that our diet modulates the complex molecular processes that have profound effects on our health and lifespan," said Siddiqi.
The findings were published in the Journal of Biological Chemistry.