Birch bark compound may fight metabolic diseases: Study

The study, published in Cell Metabolism​, reported that the birch bark compound lowered cholesterol, helped to prevent diet-induced obesity, and improved insulin sensitivity in lab mice. The betulin-treated mice were also seen to be more resistant to developing atherosclerotic plaques in their arteries.

The researchers said that betulin acts by targeting ‘sterol regulatory element-binding proteins’ (SREBPs) – a transcription factor that is known to be important in the expression of genes involved in the production of cholesterol, fatty acids, and triglycerides.

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

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

Metabolic disease​

Abnormally high levels of blood lipids (known as hyperlipidemia) is closely linked to a host of metabolic diseases, such as atherosclerosis and type II diabetes.

Hypercholesterolemia (high blood cholesterol), is typically associated with increased levels of serum cholesterol, is one of the major risk factors for atherosclerosis.

The production of blood lipids, such as cholesterol, fatty acids, and triglyceride in the body is tightly regulated by a family of transcription factors known as sterol regulatory element-binding proteins (SREBPs). In this study Song and colleagues aimed to identify and test a compound that that showed potential in blocking the SREBP pathway.

Reduced activity​

Song and colleagues initially used a chemical screening process to search for compounds that showed potential for directly blocking the action of SREBP. They reported that results from the screening process suggested betulin may work well, and so they tested its effects in a mouse model.

The team found that betulin reduced the activity of genes that are normally activated by SREBP, and was seen to lower lipid levels within cells.

They then treated mice – fed a high-fat Western diet – with betulin, a cholesterol-lowering statin (lovastatin), or a placebo (saline) for 6 weeks.

Compared to placebo, both lovostatin and betulin led to a reduction in weight on the high-fat diet, though the researchers noted that the reductions were achieved by different means.

Further investigations showed that betulin also lowered lipid levels in blood, liver, and fat tissue. Betulin also made the animals more sensitive to insulin, and showed a reduction in the number of atherosclerotic plaques formed.

Therapeutic strategy​

The researchers concluded that inhibition of SREBP by betulin decreased the biosynthesis of cholesterol and fatty acid, improved diet-induced obesity, decreased the lipid contents in serum and tissues, and increased insulin sensitivity.

“Our study demonstrates that inhibition SREBP pathway can be employed as a therapeutic strategy to treat metabolic diseases including type II diabetes and atherosclerosis,”​ they wrote.

Source: Cell Metabolism​
Published online ahead of print, doi: 10.1016/j.cmet.2010.12.004
“Inhibition of SREBP by a Small Molecule, Betulin, Improves Hyperlipidemia and Insulin Resistance and Reduces Atherosclerotic Plaques”​
Authors: J.J. Tang, J.G. Li, W. Qi, W.W. Qiu, P.S. Li, B.L. Li, B.L. Song