Liver Receptor Mediates Fat Metabolism

Researchers have found that the body's liver X receptor (LXR), a protein known to regulate cholesterol metabolism, is able to selectively sense the cholesterol component of a lipid-rich diet and to activate proteins that use this cholesterol to maintain the balance between storage and oxidation of dietary fat.

Investigators at the University of Texas Southwestern Medical Center (Dallas, USA) genetically engineered a line of mice lacking the gene for LXR. These animals were defective in hepatic lipid metabolism and were resistant to obesity when challenged with a diet containing both high fat and cholesterol. However, when given a high-fat diet containing no cholesterol, these mice were able to store fat. These findings were published in the April 2005 issue of Cell Metabolism.

Previous research had shown that LXRs activate the gene responsible for making SREBP-1c, a protein that is the primary component in the biochemical pathway that regulates fat metabolism. "LXR, this cholesterol sensor, is required for SREBP-1c to be expressed, to get SREBP-1c to initiate its role in regulating fat storage,” explained senior author Dr. David Mangelsdorf, professor of pharmacology and biochemistry at the University of Texas Southwestern Medical Center. "SREBP-1c had been considered the master regulator of fat synthesis, but our studies have shown that LXR is the master regulator of the master regulator. Our work suggests that fat storage is inextricably linked to the body's ability to metabolize cholesterol, and that the LXRs have evolved as the sensors that govern the unique cross between these two important metabolic pathways.”






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U. of Texas Southwestern Med. Center