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Betulin Better Than Statins for Managing Lipid Metabolism

By LabMedica International staff writers
Posted on 18 Jan 2011
A chemical found in birch tree bark has been found to dramatically lower lipid and cholesterol levels in test animals as well as increasing their sensitivity to insulin.

Betulin (lup-20(29)-ene-3beta,28-diol) is an abundant naturally occurring triterpene. More...
It is commonly isolated from the bark of birch trees and forms up to 30% of the dry weight of the extract.

Investigators at the Shanghai Institutes for Biological Sciences (China) worked with a mouse model that mimicked human obesity. Some of the animals were fed a high fat, Western-style diet. These mice were then treated with betulin, the cholesterol-lowering statin lovastatin, or a placebo (saline) for six weeks. At the end of this period the animals' weight, lipid profile, and insulin sensitivity were determined.

Results published in the January 2011 issue of the journal Cell Metabolism revealed that while both betulin and lovastatin restricted weight gain on the high-fat diet, betulin decreased lipids in liver and fat to a greater extent than lovastatin did. Betulin also improved insulin resistance through its effects on fatty acid and triglyceride synthesis.

The primary target of betulin activity was a group of regulatory proteins known as sterol regulatory element-binding proteins (SREBPs). The critical feature of the SREBP pathway is the proteolytic release of a membrane-bound transcription factor, SREBP. Proteolytic cleavage frees it to move through the cytoplasm to the nucleus. Once in the nucleus, SREBP can bind to specific DNA sequences (the sterol regulatory elements or SREs) that are found in the control regions of the genes that encode enzymes needed to make lipids. This binding to DNA leads to the increased transcription of the target genes and higher lipid levels. Betulin interferes with the SREBP pathway and decreases the biosynthesis of cholesterol and fatty acids.

"Our study shows that the SREBP pathway is a good target for several metabolic diseases," said senior author Dr. Bao-Liang Song, professor of biochemistry and cell biology at the Shanghai Institutes for Biological Sciences. "We also identify a leading compound."

"Betulin has several major metabolic effects," said Dr. Song. "Although betulin appears to have very low toxicity, future studies will need to further investigate the safety of betulin and its metabolic effects. We will also explore the possibility that a derivative of betulin might have even greater potency. That may be the path forward to move this clinically."

Related Links:
Shanghai Institutes for Biological Sciences


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