Liquorice compound lowers harmful blood fats via liver

Too many ApoB-containing lipoproteins in the bloodstream is one of the best-established risk factors for cardiovascular disease. ApoB (apolipoprotein B) is the structural backbone of every lipoprotein that carries fat to peripheral tissues. When levels are elevated, these particles accumulate in blood vessel walls and drive atherosclerosis.

Scientists screened nearly 3,000 compounds using zebrafish larvae as a live testing system. Among the hits was enoxolone, a compound derived from liquorice root. The study, published in eLife, showed that enoxolone significantly reduced ApoB levels, but only in animals with a functional copy of the liver receptor gene HNF4α (hepatocyte nuclear factor 4 alpha). Without a working version of that gene, the compound had no effect.

A liver receptor as the key mechanism

HNF4α is a nuclear receptor in liver cells that governs fat production and secretion. The finding that enoxolone acts through this protein points researchers toward a less-explored pathway. Inhibitors of HNF4α also reduced ApoB levels in the same experiments, reinforcing the proposed mechanism.

Zebrafish larvae were used because they reproduce quickly, are cost-effective to work with, and share much of the ApoB biology found in humans. Whether enoxolone is safe and effective in people remains a question for future research. This is a foundational study that maps a new mechanism rather than a clinical-stage treatment.

A new angle on lipid-lowering strategies

Most lipid-lowering drugs target LDL receptors or cholesterol synthesis. An HNF4α-based approach represents a distinct pathway. Whether it translates into therapeutic value depends on follow-up studies in mammals and humans. For longevity science, identifying a new mechanism that reduces ApoB levels is relevant: elevated ApoB is linked to accelerated vascular aging.

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