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Nitric oxide mediates endotoxin‐induced hypertriglyceridemia through its action on skeletal muscle lipoprotein lipase
Author(s) -
Picard Frédéric,
Kapur Sonia,
Perreault Mylène,
Marette André,
Deshaies Yves
Publication year - 2001
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.00-0830fje
Subject(s) - hypertriglyceridemia , lipoprotein lipase , nitric oxide , skeletal muscle , lipase , chemistry , medicine , endocrinology , pharmacology , biochemistry , enzyme , cholesterol , triglyceride
Hypertriglyceridemia (hyperTG) is a common characteristic of endotoxemia. At high doses of endotoxin, hyperTG is caused by a reduction in the activity of lipoprotein lipase (LPL), the enzyme responsible for TG intravascular clearance. The present studies were aimed at evaluating the role of nitric oxide (NO), overproduced in endotoxemia through the activation of inducible NO synthase (iNOS), in the decrease in tissue LPL activity brought about by lipopolysaccharide (LPS, 15 mg/kg). In rats, the specific iNOS inhibitor aminoguanidine (AGN, 100 mg/kg) prevented the LPS‐induced threefold elevation in plasma TG concentration, through actions that were not related to changes in hepatic TG secretion. AGN administration abrogated the LPS‐induced reduction in LPL activity in skeletal muscle but not that in white adipose tissue (WAT). Quantification of LPL mRNA revealed that AGN prevented LPS‐mediated alterations in muscle LPL activity through posttranscriptional mechanisms. The above findings were confirmed in iNOS (‐/‐) knockout mice injected with endotoxin. LPS increased plasma TG concentration in wild‐type mice by 75%, whereas hyperTG did not occur in knockout mice. Skeletal muscle LPL activity decreased by 40% in wild‐type mice but remained unchanged in knockout mice 6 h after LPS injection, whereas WAT LPL activity decreased to one‐third of control levels in both genotypes. These findings demonstrate that, after LPS administration, reduced muscle LPL activity and the resulting hyperTG are caused by the overproduction of NO via the induction of iNOS. The findings further provide evidence for a central role of muscle LPL in the response of TG metabolism to acute endotoxemia.