Lysosomal acid lipase (LAL) supplementation may have some lipidemic benefits, according to the results of a mouse model study which will be presented at the 18th Annual WORLDSymposium in San Diego, CA between February 7 and 11, 2022.

The LAL enzyme is responsible for converting cholesterol esters and triglycerides into free cholesterol and free fatty acids. In patients with LAL deficiency (LAL-D), cholesterol esters and triglycerides accumulate in different organs, especially the liver, leading to the symptoms of the disease.

Here, a team of researchers led by Katherine D. Cygnar, PhD, the director of Regeneron Pharmaceuticals, Inc., showed that adeno-associated virus vector serotype 8 (AAV8)-mediated LAL liver depot gene therapy could effectively clear lipid accumulation in a mouse model of LAL-D.

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“Surprisingly, LAL-D model mice treated with long-term LAL gene therapy had better liver condition with lower triglyceride content than their wild type littermates,” the researchers wrote. 

Read more about LAL-D etiology

They also speculated that LAL supplementation could reverse or prevent the worsening of fatty liver disease in a setting without LAL-D based on the evidence that patients with nonalcoholic fatty liver disease also have low LAL activity.

To test their hypothesis, the researchers treated mice with diet-induced obesity with AAV8-mediated human LAL under the control of a liver-specific promoter. They found that this significantly reduced serum triglyceride, cholesterol, and low-density lipoprotein levels compared to those of control animals.

They concluded that LAL supplementation may have some lipidemic benefits. They also found a trend towards lower weight gain and lower liver lipid content in LAL-supplemented obese mice, although this was not statistically significant. 

“While LAL supplementation falls short of treating [nonalcoholic fatty liver disease], the data suggests that there may be some metabolic benefits to enhanced LAL activity which should be further investigated,” the researchers said.


Aaron NA, Baik AD, Economides AN, Cygnar KD. Liver-specific AAV gene therapy corrects lipid storage in LAL-D model mice but does not prevent lipid accumulation in acquired fatty liver model mice. Mol Genet Metab. 2022;135(2):S15. doi:10.1016/j.ymgme.2021.11.016