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New Compound Reverses Fatty Liver Disease

Treatment targets proteins responsible for fat production (Dec. 19)

Scientists on the Florida campus of the Scripps Research Institute have developed the first synthetic compound that can reverse the effects of a serious metabolic condition, fatty liver disease. As its name implies, the disease is characterized by an abnormal buildup of fat in the liver.

The new compound — known as SR9238 — is the first to suppress effectively lipid or fat production in the liver, thereby eliminating inflammation and reversing fat accumulation in animal models of fatty liver disease. The new compound also significantly lowered total cholesterol levels, although precisely how that occurred remains a mystery.

“We’ve been working on a pair of natural proteins called LXR-alpha and LXR-beta that stimulate fat production in the liver, and we thought our compound might be able to successfully suppress this process,” said lead investigator Professor Thomas Burris. “Once the animals were put on the drug, we were able to reverse the disease after a single month with no adverse side effects while they ate a high-fat diet.”

The new study was published online in ACS Chemical Biology.

Fatty liver, which often accompanies obesity and type 2 diabetes, often leads to more serious conditions, including cirrhosis and liver cancer. The condition affects approximately 10% to 24% of the general population, according to a 2003 study in the journal Gut.

Burris and his colleagues designed SR9238 so that it would be quickly metabolized in the liver to minimize migration of the drug into the bloodstream, which could lead to side effects.

In the study, mice were fed a high-fat diet for 14 weeks before treatment with SR9238. After 1 month, the scientists found that the liver’s fat-producing genes were repressed and that fat expression in the liver was reduced by up to 90%.

In addition, the researchers observed an 80% reduction of the enzyme responsible for producing cholesterol (3-hydroxy-3-methylglutaryl coenzyme A reductase) — the same enzyme targeted by statins.

Markers for liver damage were down as well, which suggests that the compound may also have the potential to treat alcohol-related fatty liver damage, according to the investigators.

Source: Scripps Research Institute; December 19, 2012.

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