Endotoxin rapidly induces changes in lipid metabolism that produce hypertriglyceridemia: low doses stimulate hepatic triglyceride production while high doses inhibit clearance.

作者：KR Feingold, Ilona Staprãns, RA Memon, A H Moser, JK Shigenaga, William T. Doerrler, CA Dinarello, Carl Grünfeld · 发表于：Journal of Lipid Research · 年份：1992 · DOI：10.1016/s0022-2275(20)41334-3 · 被引用次数：352 · 研究领域：Peroxisome Proliferator-Activated Receptors、Lipid metabolism and disorders、Adipokines, Inflammation, and Metabolic Diseases

Hyperlipidemia frequently accompanies infectious diseases and may be due to increases in lipoprotein production or decreases in lipoprotein clearance. The administration of endotoxin (LPS) has been used to mimic infection and prior studies demonstrate that LPS produces hypertriglyceridemia. In the present study in rodents, the dose of LPS necessary to induce hyperlipidemia was orders of magnitude less than that necessary to induce shock and death. As little as 10 ng/100 g body weight induced hypertriglyceridemia and this increase in serum triglyceride levels occurred rapidly (78% increase at 2 h). At high doses of LPS (50 micrograms/100 g body weight), the clearance of triglyceride-rich lipoproteins was decreased. At low doses of LPS (100 ng/100 g body weight), triglyceride clearance was not altered but the hepatic secretion of triglyceride was increased. Low dose LPS stimulated hepatic de novo fatty acid synthesis and lipolysis, both of which provided a source of fatty acids for the increase in hepatic triglyceride production. High dose LPS did not increase hepatic fatty acid synthesis or peripheral lipolysis, and hepatic triglyceride secretion was not stimulated. Thus, low dose LPS produces hypertriglyceridemia by increasing hepatic lipoprotein production, while high dose LPS produces hypertriglyceridemia by decreasing lipoprotein catabolism. Administration of anti-tumor necrosis factor (TNF) antibodies or interleukin 1 (IL-1) receptor antagonist did not prevent the increas...