Lecithin Found to Help Modulate Lipid Metabolism

Activating PPARs induces the transcription of a number of genes that facilitate lipid metabolism.

Investigators from Washington University School of Medicine (St. Louis, MO, USA) genetically engineered a line of mice to lack the gene for the enzyme fatty acid synthase (FAS). Results published in the July 30, 2009, online issue of the journal Cell revealed that these mice had lower fasting insulin levels than normal animals and were prone to develop fatty liver disease. These were the same indications that coincided with impaired PPAR-alpha expression.

While it was known that fibrate drugs could activate PPAR-alpha and restore normal lipid metabolism, the investigators sought an endogenous ligand that could perform the same function. To this end, they used mass spectroscopy and gene expression analysis to demonstrate that the lecithin component phosphatidylcholine (1-palmitoyl-2-oleoyl-sn-glycerol-3-phosphocholine) could bind to and activate PPAR-alpha. This finding was confirmed by showing that "knockdown” of the Cept1 gene, required for phosphatidylcholine synthesis, suppressed PPAR-alpha-dependent gene expression.

"To our surprise, animals missing fatty acid synthase in the liver were just like animals that could not make PPAR-alpha. They had lower fasting insulin levels, and they were prone to develop fatty liver disease,” explained senior author Dr. Clay F. Semenkovich, professor of endocrinology, metabolism, and lipid research at Washington University School of Medicine. "When we gave the animals fibrate drugs that activated PPAR-alpha, the mice returned to normal, leading us to suspect that fatty acid synthase also was involved in the activation of PPAR-alpha. Although we knew that fibrate drugs would regulate PPAR-alpha, we also knew that our ability to regulate the metabolism of fats and sugars was in place long before humans started making drugs. But until now, no one had identified how it worked.”

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Washington University School of Medicine