Birch bark ingredient comes with many metabolic
benefits

Cell Press

Elisabeth Lyons

4-Jan-2011

An ingredient found in abundance in birch bark
appears to have an array of metabolic benefits, according to new studies in
animals that are reported in the January issue of Cell Metabolism, a
Cell Press publication. In mice, the compound known as betulin lowered cholesterol, helped prevent diet-induced obesity, and
improved insulin sensitivity. Betulin-treated mice
were also more resistant to developing atherosclerotic plaques in their
arteries.

Betulin works by targeting so-called sterol regulatory element-binding
proteins (SREBPs), transcription factors that are
known to be important for activating the expression of genes involved in the
biosynthesis of cholesterol, fatty acids, and triglycerides.

"Our study shows that the SREBP
pathway is a good target for several metabolic diseases," said Bao-Liang Song of the Shanghai Institutes for Biological
Sciences. "We also identify a leading compound."

In the new study, Song and his
colleagues went in search of a compound that might act directly on SREBP. That
chemical screen turned up betulin as a top contender. They then
confirmed in cells that betulin lowered the activity of genes that are
normally switched "on" by SREBP. It also lowered lipid levels within
cells.

Song's team then treated mice on a
high-fat, Western diet with betulin, the cholesterol-lowering statin known as lovastatin, or a
placebo (saline) for 6 weeks. Compared to placebo, both drugs led the mice to
gain less weight on the high-fat diet, though by different means. Betulin caused the animals to burn more calories while lovastatin appeared to reduce the amount of lipid taken up
from the diet.

Further investigations showed that betulin also lowered lipid levels in blood, liver, and fat tissue. Betulin also made the animals more sensitive to insulin.
Mice with a mutation that makes them prone to develop atherosclerosis showed
fewer plaques when treated with either lovastatin or betulin.

"Betulin has several major metabolic effects," Song said.

The researchers say that their findings
suggest that betulin may have similar or even better
effects than lovastatin, a member of the most widely
prescribed drug class for treating high cholesterol. For instance, in their
studies 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.

Song notes that betulin is a readily available compound and is already in use as a
precursor in the manufacture of other drugs.

Although betulin appears to have very low toxicity, he says future studies will
need to further investigate the safety of betulin and its metabolic effects. Researchers 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," Song said.