Newly Identified Protein HELZ2 Regulates Cholesterol Release from Liver
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Researchers have discovered a protein, HELZ2, that controls how the liver releases cholesterol-carrying particles into the bloodstream. In mice, increased HELZ2 activity reduced blood cholesterol and triglycerides, offering greater protection against atherosclerosis, but also led to fat accumulation in the liver. The finding, published in the journal Circulation, reveals a new potential target for managing cholesterol levels.
Facts First
- HELZ2 protein regulates cholesterol release by controlling the stability of APOB messenger RNA in liver cells.
- Increased HELZ2 activity in mice lowered blood cholesterol and triglycerides and provided greater protection against atherosclerosis.
- The same mutation that lowered blood cholesterol caused increased fat accumulation in the liver of the mice.
- The discovery was made using a large-scale genetic screening system developed by Nobel laureate Bruce Beutler, M.D.
- The research points to a new potential target for therapies aimed at managing cholesterol and heart disease risk.
What Happened
Researchers at UT Southwestern Medical Center identified a protein called HELZ2 that regulates how the liver releases cholesterol-carrying particles into the bloodstream. The study, published in the American Heart Association journal Circulation, found that HELZ2 controls the activity of the apolipoprotein B (APOB) gene, which is required to produce proteins that form lipoproteins. HELZ2 functions by shortening the lifespan of APOB messenger RNA (mRNA) inside liver cells, leading to lower production of cholesterol-carrying lipoproteins. While studying unusual fat buildup in the livers of mice, scientists identified a gain-of-function mutation that increased HELZ2 activity. Mice with this mutation produced fewer lipoproteins, including low-density lipoprotein (LDL) cholesterol and triglycerides, in their bloodstream.
Why this Matters to You
This discovery reveals a new biological mechanism for controlling cholesterol, a major factor in heart disease. While statins are the most widely prescribed drugs for lowering cholesterol, this research could lead to the development of new therapies that target the HELZ2 pathway. Such future treatments might offer an alternative or complementary approach to managing your cholesterol levels and reducing your risk of atherosclerosis. However, the finding also highlights a potential trade-off, as the mouse model showed that lowering blood cholesterol via this mechanism may lead to increased fat in the liver.
What's Next
The identification of HELZ2 as a regulator of cholesterol release opens a new avenue for research. Scientists are likely to investigate whether modulating HELZ2 activity in humans could safely lower blood cholesterol without causing harmful liver fat accumulation. This research could eventually inform the development of novel drugs. The work was supported by National Institutes of Health (NIH) grants, indicating ongoing federal investment in this line of inquiry.