Syndrome X Linked to Several Illnesses


The metabolic syndrome, sometimes referred to as syndrome X, is characterized by multiple risk factors. The underlying causes are obesity, physical inactivity, and genetic factors. The characteristic disorders present in the metabolic syndrome include (1) excessive fat tissue in and around the abdomen, (2) high blood pressure, (3) insulin resistance or glucose intolerance, (4) blood fat disorders, especially high levels of triglycerides and low levels of high-density lipoproteins ("good" cholesterol), and (5) abnormalities in blood clotting.

Any one of these disorders by itself is a risk for certain diseases, but in combination they can dramatically boost the risk of life-threatening illnesses, said Dr. Mangelsdorf, an investigator at Howard Hughes Medical Institute, University of Texas Southwestern Medical Center:

"One person may have a more severe case of type 2 diabetes,
for example, or another person may not have hypertension,
yet they may all have the syndrome. There's not one factor
that overrides everything else. Lipid, or fat, metabolism
is an important component, however, and in fact, lipid
metabolism may drive the syndrome. The question is, why?"
The answer may lie in his research that has identified the protein retinoid X receptor (RXR), which plays a key role in lipid metabolism. This protein can bind to several other nuclear receptors to form distinct molecular complexes called heterodimers. Each complex then can go on to control certain genes involved in regulating lipid and cholesterol metabolism.

"When RXR is paired with a nuclear receptor called PPAR-gamma, for example, it activates one set of genes," Dr. Mangelsdorf said. "When RXR is paired with another receptor called LXR, it acts on a different set of genes. All of the genes, however, are involved with lipid metabolism."

(Source: New England Journal of Medicine, August 11, 2005.)

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