Lymphotoxin beta receptor-dependent control of lipid homeostasis.
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.
Lo
James C
JC
Committee on Immunology, University of Chicago, Chicago, IL 60637, USA.
Wang
Yugang
Y
Tumanov
Alexei V
AV
Bamji
Michelle
M
Yao
Zemin
Z
Reardon
Catherine A
CA
Getz
Godfrey S
GS
Fu
Yang-Xin
YX
D000818:Animals; D002478:Cells, Cultured; D050171:Dyslipidemias / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism; D005260:Female; D006706:Homeostasis; D006801:Humans; D006937:Hypercholesterolemia / Q000209:etiology; D050356:Lipid Metabolism; D008055:Lipids / Q000097:blood; D008099:Liver / Q000378:metabolism*; D053259:Lymphotoxin beta Receptor / Q000378:metabolism* / Q000627:therapeutic use; D008233:Lymphotoxin-alpha / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000378:metabolism; D053326:Tumor Necrosis Factor Ligand Superfamily Member 14 / Q000235:genetics / Q000378:metabolism* / Q000627:therapeutic use
D008055:Lipids; D053259:Lymphotoxin beta Receptor; D008233:Lymphotoxin-alpha; C505915:Tnfsf14 protein, mouse; D053326:Tumor Necrosis Factor Ligand Superfamily Member 14