UNIGE document Scientific Article
previous document  unige:84728  next document
add to browser collection
Title

Acipimox reduces circulating levels of insulin and associated neutrophilic inflammation in metabolic syndrome

Authors
Bertolotto, Maria
Franciosi, Ulisse
Puddu, Alessandra
Minetti, Silvia
Delrio, Andrea
show hidden authors show all authors [1 - 16]
Published in American Journal of Physiology. Endocrinology and Metabolism. 2011, vol. 300, no. 4, p. E681-90
Abstract Metabolic syndrome is a proatherosclerotic condition clustering cardiovascular risk factors, including glucose and lipid profile alterations. The pathophysiological mechanisms favoring atherosclerotic inflammation in the metabolic syndrome remain elusive. Here, we investigated the potential role of the antilipolytic drug acipimox on neutrophil- and monocyte-mediated inflammation in the 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 2-5 h afterward 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 toward the proatherosclerotic chemokine CCL3. Two to five hours after acipimox administration, a significant reduction in circulating levels of insulin and nonesterified fatty acid (NEFA) was shown in metabolic syndrome patients. At time 0 and 2 h after acipimox administration, metabolic syndrome serum increased neutrophil migration to CCL3 compared with 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 upregulate CCR5 expression on neutrophil surface membrane, but it increased intracellular JNK1/2 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 proatherosclerotic functions in the metabolic syndrome through the reduction in circulating levels of insulin.
Keywords Administration, OralAdultAlgorithmsCells, CulturedDown-Regulation/drug effectsFemaleHumansHypolipidemic Agents/administration & dosage/pharmacologyInflammation/blood/complications/immunology/prevention & controlInsulin/blood/metabolismMaleMetabolic Syndrome X/blood/complications/drug therapy/immunologyMiddle AgedNeutrophils/immunology/physiologyPyrazines/administration & dosage/pharmacologyTime Factors
Identifiers
PMID: 21266669
Full text
Article (Published version) (489 Kb) - document accessible for UNIGE members only Limited access to UNIGE
Structures
Research group Chimie et protéomique clinique (270)
Citation
(ISO format)
MONTECUCCO, Fabrizio et al. Acipimox reduces circulating levels of insulin and associated neutrophilic inflammation in metabolic syndrome. In: American Journal of Physiology. Endocrinology and Metabolism, 2011, vol. 300, n° 4, p. E681-90. https://archive-ouverte.unige.ch/unige:84728

225 hits

0 download

Update

Deposited on : 2016-06-24

Export document
Format :
Citation style :