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Triacsin C Suppresses Non‐Esterified Fatty Acids (NEFA) and Increases Nitric Oxide (NO) Synthesis
Author(s) -
Blakeman Nina Ruth,
Trepanier Marc-Olivier,
Bazinet Richard P.,
Weis Margaret T.
Publication year - 2012
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/fasebj.26.1_supplement.lb456
Subject(s) - nefa , enos , hyperlipidemia , medicine , chemistry , endocrinology , nitric oxide , fatty acid , nitric oxide synthase , biochemistry , diabetes mellitus
Endothelial dysfunction is characterized by decreased vascular NO availability. Elevated NEFA decreases eNOS activity. In cultured cells, we found that fatty acyl CoA synthase (FACS) inhibitor Triacsin C (TC) interrupted eNOS palmitoylation, increasing eNOS activity but not changing vascular‐active eicosanoids. Hypothesis: TC mitigates endothelial dysfunction by increasing NO and decreasing NEFA. In this study, intravascular NO synthesis was measured by electrochemistry in the ischemic hind limb with heparinized rat model in a time course design. The post‐ischemic NO was significantly elevated in TC (100 μg/kg)‐treated animals than controls. NOS inhibitor treatments in this model implicate a role of eNOS, but not iNOS. Acute hyperlipidemia was induced by a bolus dose of Intralipid ® (1 ml) to increase NEFA. Pre‐treatment with TC had no effect on total plasma lipids or triglycerides, either before or after Intralipid ® . TC reduced baseline plasma NEFA from 240 ± 26.8 to 147 ± 14.3 μg/ml (p=0.038). Fifteen minutes after Intralipid ® , NEFA rose to 1461 ± 130 μg/ml (control), which was blunted by TC to 393 ± 2.55 μg/ml (p=0.0079). By 85 min., the difference had subsided (194 ± 10.2 control vs . 281 ± 74.8 μg/ml TC; p=0.74). The TC effect was not uniform across all fatty acid species measured. These data show that TC increases post‐ischemic eNOS activity and blunted plasma NEFA induced by acute hyperlipidemia.