One drug fights fat and diabetes in mice

Researchers searching for a cure for obesity said on Thursday they have developed a drug that not only makes mice lose weight, but reverses diabetes and lowers their cholesterol, too.

The drug, which they have dubbed fatostatin, stops the body from making fat, instead releasing the energy from food. They hope it may lead to a pill that would fight obesity, diabetes and cholesterol, all at once.

Writing in the journal Chemistry and Biology, Salih Wakil of Baylor College of Medicine in Texas, Motonari Uesugi of Kyoto University in Japan and colleagues said the drug interferes with a suite of genes turned on by overeating.

“Here, we are tackling the basics,” Wakil said in a telephone interview. “I think that is what excited us.”

Scientists are painfully aware that drugs that can make mice thin do nothing of the sort in humans. A hormone called leptin can make rats and mice drop weight almost miraculously but does little or nothing for an obese person, for instance.

But Wakil, whose team has patented the drug and is looking for a drug company to partner with, hopes this drug may be different. “I am very, very optimistic,” he said.

Fatostatin is a small molecule, meaning it has the potential to be absorbed in pill form.

It works on so-called sterol regulatory element binding proteins or SREBPs, which are transcription factors that activate genes involved in making cholesterol and fatty acids.

“Fatostatin blocked increases in body weight, blood glucose, and hepatic (liver) fat accumulation in (genetically) obese mice, even under uncontrolled food intake,” the researchers wrote.

Genetic tests showed the drug affected 63 different genes.

The idea of interfering with SREBP is not new. GlaxoSmithKline has been working on a new-generation cholesterol drug that uses this pathway.

After four weeks, mice injected with fatostatin weighed 12 percent less and had 70 percent lower blood sugar levels, the researchers wrote.

Now they plan to test rats and rabbits, Wakil said.

The drug also had effects on prostate cancer cells they said—something that may help explain links between prostate cancer and obesity.

SOURCE: Chemistry and Biology, August 28, 2009.