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Sugars in Liver Found to Clear Fats from the Bloodstream

esearchers made mutations in only in the liver, because such mutations throughout all tissues would lead to the death of an embryo or death shortly after birth.

“By selectively mutating a single tissue in mice, in this case the liver, we avoided a lethal effect,” said Esko. In the lab, the researchers combined the heparan sulfate mutation with a mutation in the LDL receptor, which has long known to be responsible for clearing cholesterol from the arteries. The UCSD team showed that heparan sulfate is involved in clearing not only triglycerides, but also cholesterol, from the blood.

“The finding, that the LDL receptor plus heparan sulfate work together to clear triglyceride and cholesterol-rich particles from the blood in a healthy person is very exciting,” Esko said. The study suggests the possibility that mutations in one of 40 or so genes involved in production of heparan sulfate in the liver could result in high blood-fat levels and lead to complications such as arthrosclerosis, according to Esko.

In animal models with induced diabetes, changes in liver heparan sulfate – consistent with the UCSD researchers’ findings – often appear. One of the team’s next steps will be to induce diabetes in animals and examine the role of heparan sulfate in more detail.

“Such studies could lead to new drugs that change heparan sulfate in order to lower fat levels in patients,” said Esko.

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