Publication Date:
2007-04-14
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lo, James C -- Wang, Yugang -- Tumanov, Alexei V -- Bamji, Michelle -- Yao, Zemin -- Reardon, Catherine A -- Getz, Godfrey S -- Fu, Yang-Xin -- 5 T32 GM07281/GM/NIGMS NIH HHS/ -- AI062026/AI/NIAID NIH HHS/ -- CA097296/CA/NCI NIH HHS/ -- DK58891/DK/NIDDK NIH HHS/ -- HL 85516/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 2007 Apr 13;316(5822):285-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Committee on Immunology, University of Chicago, Chicago, IL 60637, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17431181" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Cells, Cultured
;
Dyslipidemias/drug therapy/etiology/metabolism
;
Female
;
Homeostasis
;
Humans
;
Hypercholesterolemia/etiology
;
*Lipid Metabolism
;
Lipids/blood
;
Liver/*metabolism
;
Lymphotoxin beta Receptor/*metabolism/therapeutic use
;
Lymphotoxin-alpha/metabolism
;
Male
;
Mice
;
Mice, Inbred C57BL
;
Signal Transduction
;
T-Lymphocytes/metabolism
;
Tumor Necrosis Factor Ligand Superfamily Member
;
14/genetics/*metabolism/therapeutic use
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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