Deregulation of hepatic insulin sensitivity induced by central lipid infusion in rats is mediated by nitric oxide.
Deregulation of hypothalamic fatty acid sensing lead to hepatic insulin-resistance which may partly contribute to further impairment of glucose homeostasis.We investigated here whether hypothalamic nitric oxide (NO) could mediate deleterious peripheral effect of central lipid overload. Thus we infus...
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2009-08-01
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doaj-e8b413eddeff4419be13831276fce8152020-11-24T20:49:54ZengPublic Library of Science (PLoS)PLoS ONE1932-62032009-08-0148e664910.1371/journal.pone.0006649Deregulation of hepatic insulin sensitivity induced by central lipid infusion in rats is mediated by nitric oxide.Nicolas MarsollierNadim KassisKarima MezghennaMaud SotyXavier FioramontiAmélie LacombeAurélie JolyBruno PillotCarine ZitounJosé VilarGilles MithieuxRené GrossAnne-Dominique LajoixVanessa RouthChristophe MagnanCéline Cruciani-GuglielmacciDeregulation of hypothalamic fatty acid sensing lead to hepatic insulin-resistance which may partly contribute to further impairment of glucose homeostasis.We investigated here whether hypothalamic nitric oxide (NO) could mediate deleterious peripheral effect of central lipid overload. Thus we infused rats for 24 hours into carotid artery towards brain, either with heparinized triglyceride emulsion (Intralipid, IL) or heparinized saline (control rats).Lipids infusion led to hepatic insulin-resistance partly related to a decreased parasympathetic activity in the liver assessed by an increased acetylcholinesterase activity. Hypothalamic nitric oxide synthases (NOS) activities were significantly increased in IL rats, as the catalytically active neuronal NOS (nNOS) dimers compared to controls. This was related to a decrease in expression of protein inhibitor of nNOS (PIN). Effect of IL infusion on deregulated hepatic insulin-sensitivity was reversed by carotid injection of non selective NOS inhibitor NG-monomethyl-L-arginine (L-NMMA) and also by a selective inhibitor of the nNOS isoform, 7-Nitro-Indazole (7-Ni). In addition, NO donor injection (L-arginine and SNP) within carotid in control rats mimicked lipid effects onto impaired hepatic insulin sensitivity. In parallel we showed that cultured VMH neurons produce NO in response to fatty acid (oleic acid).We conclude that cerebral fatty acid overload induces an enhancement of nNOS activity within hypothalamus which is, at least in part, responsible fatty acid increased hepatic glucose production.http://europepmc.org/articles/PMC2721417?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Nicolas Marsollier Nadim Kassis Karima Mezghenna Maud Soty Xavier Fioramonti Amélie Lacombe Aurélie Joly Bruno Pillot Carine Zitoun José Vilar Gilles Mithieux René Gross Anne-Dominique Lajoix Vanessa Routh Christophe Magnan Céline Cruciani-Guglielmacci |
spellingShingle |
Nicolas Marsollier Nadim Kassis Karima Mezghenna Maud Soty Xavier Fioramonti Amélie Lacombe Aurélie Joly Bruno Pillot Carine Zitoun José Vilar Gilles Mithieux René Gross Anne-Dominique Lajoix Vanessa Routh Christophe Magnan Céline Cruciani-Guglielmacci Deregulation of hepatic insulin sensitivity induced by central lipid infusion in rats is mediated by nitric oxide. PLoS ONE |
author_facet |
Nicolas Marsollier Nadim Kassis Karima Mezghenna Maud Soty Xavier Fioramonti Amélie Lacombe Aurélie Joly Bruno Pillot Carine Zitoun José Vilar Gilles Mithieux René Gross Anne-Dominique Lajoix Vanessa Routh Christophe Magnan Céline Cruciani-Guglielmacci |
author_sort |
Nicolas Marsollier |
title |
Deregulation of hepatic insulin sensitivity induced by central lipid infusion in rats is mediated by nitric oxide. |
title_short |
Deregulation of hepatic insulin sensitivity induced by central lipid infusion in rats is mediated by nitric oxide. |
title_full |
Deregulation of hepatic insulin sensitivity induced by central lipid infusion in rats is mediated by nitric oxide. |
title_fullStr |
Deregulation of hepatic insulin sensitivity induced by central lipid infusion in rats is mediated by nitric oxide. |
title_full_unstemmed |
Deregulation of hepatic insulin sensitivity induced by central lipid infusion in rats is mediated by nitric oxide. |
title_sort |
deregulation of hepatic insulin sensitivity induced by central lipid infusion in rats is mediated by nitric oxide. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2009-08-01 |
description |
Deregulation of hypothalamic fatty acid sensing lead to hepatic insulin-resistance which may partly contribute to further impairment of glucose homeostasis.We investigated here whether hypothalamic nitric oxide (NO) could mediate deleterious peripheral effect of central lipid overload. Thus we infused rats for 24 hours into carotid artery towards brain, either with heparinized triglyceride emulsion (Intralipid, IL) or heparinized saline (control rats).Lipids infusion led to hepatic insulin-resistance partly related to a decreased parasympathetic activity in the liver assessed by an increased acetylcholinesterase activity. Hypothalamic nitric oxide synthases (NOS) activities were significantly increased in IL rats, as the catalytically active neuronal NOS (nNOS) dimers compared to controls. This was related to a decrease in expression of protein inhibitor of nNOS (PIN). Effect of IL infusion on deregulated hepatic insulin-sensitivity was reversed by carotid injection of non selective NOS inhibitor NG-monomethyl-L-arginine (L-NMMA) and also by a selective inhibitor of the nNOS isoform, 7-Nitro-Indazole (7-Ni). In addition, NO donor injection (L-arginine and SNP) within carotid in control rats mimicked lipid effects onto impaired hepatic insulin sensitivity. In parallel we showed that cultured VMH neurons produce NO in response to fatty acid (oleic acid).We conclude that cerebral fatty acid overload induces an enhancement of nNOS activity within hypothalamus which is, at least in part, responsible fatty acid increased hepatic glucose production. |
url |
http://europepmc.org/articles/PMC2721417?pdf=render |
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