Liver Chemical Crucial in Keeping Blood Fats Low

Dramatic underproduction of a particular liver biochemical seems to be the cause of the pathologically high blood-fat levels associated with type 2 diabetes and metabolic syndrome in obese mice, a recent study found. Metabolic syndrome is a disorder that places its sufferers at greatly increased risk for cardiovascular disease, and is marked by the intersection of several symptoms, including belly obesity, high blood pressure and high blood fats.     The research, done by Stephan Herzig and his colleagues at the German Cancer Research Center (Deutsches Krebsforschungszentrum, or DKFZ), was published in the journal Diabetes .

The key biochemical is a lipid (fat) transporter known as LSR (short for lipolysis-stimulated lipoprotein receptor), which is found in the bowel and especially the liver. It’s responsible for the transfer of fat from the blood to liver tissue. Herzig found that, in obese mice with type 2 diabetes, the liver’s LSR production is sharply reduced. Thus, fat that should be removed from the blood and brought to the liver, isn’t, leading to high blood-fat levels.
   
The scientists then restored normal liver LSR levels by giving the diabetic mice leptin, a hormone that suppresses appetite. The obese leptin-treated mice lost striking amounts of weight (as much as 30 percent of their body weight), their livers secreted LSR in healthy quantities, and their blood-fat levels fell to normal. LSR also promotes fat breakdown in the liver.

“Thus, we have shown for the first time that the LSR molecule plays a central role in lipid metabolism,” Herzig said. “We were also able to provide evidence that apparently it depends on body weight how much LSR is produced in the liver: being overweight is associated with reduced production.”

The research team concluded that manipulating LSR levels should be considered as a possible target for treating metabolic syndrome and type 2 diabetes. The need is great for such approaches, for estimates are that some 300 million people around the world will have developed type 2 diabetes in a year’s time.

“If we were able to increase hepatic [liver] LSR production in these patients, this would relieve essential aspects of this disease,” said Herzig.


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