| Acipimox reduces circulating levels of insulin and associated neutrophilic inflammation in metabolic syndrome. | |
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MedLine Citation:
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PMID: 21266669 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Metabolic syndrome is a pro-atherosclerotic condition clustering cardiovascular risk factors, including glucose and lipid profile alterations. The pathophysiological mechanisms favoring atherosclerotic inflammation in metabolic syndrome remain elusive. Here, we investigated the potential role of the anti-lipolytic drug Acipimox on neutrophil- and monocyte-mediated inflammation in metabolic syndrome. Acipimox (500 mg) was orally administered to metabolic syndrome patients (n=11) or healthy controls (n=8). Serum and plasma was collected before Acipimox administration (time 0) as well as 2h-5h after to assess metabolic and hematologic parameters. In vitro, the effects of the incubation with metabolic syndrome serum were assessed on human neutrophil and monocyte migration towards the pro-atherosclerotic chemokine CCL3. 2h-5h after Acipimox administration, a significant reduction of circulating levels of insulin and nonesterified fatty acid (NEFA) was shown in metabolic syndrome patients. At time 0 and 2h after Acipimox administration, metabolic syndrome serum increased neutrophil migration to CCL3 as compared to healthy controls. No effect was shown in human monocytes. At these time points, serum-induced neutrophil migration positively correlated with serum levels of insulin and NEFA. Metabolic syndrome serum or recombinant insulin did not up regulate CCR5 expression on neutrophil surface membrane, but increased intracellular JNK 1/2 phosphorylation. Insulin immunodepletion blocked serum-induced neutrophil migration and associated JNK1/2 phosphorylation. Although mRNA expression of Acipimox receptor (GPR109) was shown in human neutrophils, 5-500 μM Acipimox did not affect insulin-induced neutrophil migration. In conclusion, results suggest that Acipimox inhibited neutrophil pro-atherosclerotic functions in metabolic syndrome through the reduction of circulating levels of insulin. |
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Authors:
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Fabrizio Montecucco; Maria Bertolotto; Nicolas Vuilleumier; Ulisse Franciosi; Alessandra Puddu; Silvia Minetti; Andrea Delrio; Alessandra Quercioli; Ettore Bergamini; Luciano Ottonello; Aldo Pende; Sébastien Lenglet; Graziano Pelli; François Mach; Franco Dallegri; Giorgio Viviani |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-1-25 |
Journal Detail:
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Title: American journal of physiology. Endocrinology and metabolism Volume: - ISSN: 1522-1555 ISO Abbreviation: - Publication Date: 2011 Jan |
Date Detail:
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Created Date: 2011-1-26 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 100901226 Medline TA: Am J Physiol Endocrinol Metab Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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1University of Geneva. |
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