Lowering lipid absorption in mice points to a treatment for hyperlipidemia

Researchers have identified an enzyme that, when inhibited, significantly reduced lipid absorption in mice. If developed as treatment for hyperlipidemia in humans, it could be used as a substitute or as an additional treatment to statin therapy to combat cardiovascular disease, according to a study published online September 3, 2015 in Gastroenterology.

“Hyperlipidemia…is a common disease and contributes significantly to cardiac-related morbidity and mortality,” said lead investigator Xian-Cheng Jiang, PhD, professor of cell biology at SUNY Downstate Medical Center, in Brooklyn, NY. He noted that trials of statin drugs—the mainstay of clinical management of cardiovascular disease—have proven the benefits of reducing low-density lipoprotein (LDL).

“However, there are many instances in which patients do not respond to or cannot tolerate statins,” he said. Because of this, additional approaches to lower plasma lipid are urgently needed, preferably ones that act synergistically with statins.

In this experiment, Dr. Jiang and colleagues bred mice that lacked the gene to produce LPCAT3, an enzyme involved in the biosynthesis of a compound lipid that is a major component of cell membranes. They found that the knockout mice showed reduced intestinal uptake of lipids by the small intestine, as well as reduced plasma levels of cholesterol, phospholipid, and triglyceride.

The researchers concluded that inhibiting LPCAT3 in the small intestine could be developed as an approach to treat hyperlipidemia.

“Our study is intended to provide a novel approach to reduce the ‘bad’ lipids in the blood,” Dr. Jiang said. “Although the study was conducted in a mouse model, the outcomes may be applicable to humans.”