Journal
SCIENCE
Volume 316, Issue 5822, Pages 285-288Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.1137221
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Hyperlipidemia, one of the most important risk factors for coronary heart disease, is often associated with inflammation. We identified lymphotoxin ( LT) and LIGHT, tumor necrosis factor cytokine family members that are primarily expressed on lymphocytes, as critical regulators of key enzymes that control lipid metabolism. Dysregulation of LIGHT expression on T cells resulted in hypertriglyceridemia and hypercholesterolemia. In low-density lipoprotein receptor-deficient mice, which lack the ability to control lipid levels in the blood, inhibition of LT and LIGHT signaling with a soluble lymphotoxin beta receptor decoy protein attenuated the dyslipidemia. These results suggest that the immune system directly influences lipid metabolism and that LT modulating agents may represent a novel therapeutic route for the treatment of dyslipidemia.
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