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Our working hypothesis postulates that lipolysis is a determinant of inflammation in adipose tissue (AT). Inhibition of lipolysis, e.g. using the oldest normolipidemic drug, nicotinic acid, has proved valuable to combat the metabolic syndrome. Our proposal will determine whether part of the beneficial effects of this antilipolytic compound is due to a diminution of AT inflammation.
To this aim, the effect of nicotinic acid or placebo will be studied in male obese subjects with or without a training program which goal is to enhance lipolysis.
24 male obese insulin resistant subjects will receive nicotinic acid or placebo for 16 weeks. The last 8 weeks, the subjects will follow a training program calculated to optimize use of lipid. Insulin sensitivity and glucose tolerance will be assessed using, respectively, fasting-based estimates of insulin sensitivity (plasma and muscle) and oral glucose tolerance test. Plasma parameters of adipokines and, inflammatory and metabolic parameters will be determined. As an index of AT inflammation, the percentage and the phenotype of macrophages will be determined using flow cytometry of cells of the stromavascular fraction of subcutaneous AT. Macrophage infiltration will be investigated by light microscopy. The characterization of the inflammatory profile of AT will be completed by measurements of the expression of genes that are either specific markers of human AT macrophages or inflammatory and anti-inflammatory adipokines. This combination of approaches has never been carried out during a pharmacological intervention in humans. The following points will be addressed:
- determine the influence of lipolysis on AT inflammation, specifically on macrophage activation and adipokine production.
- examine the causal relationship between adipocyte FA metabolism, AT inflammation and insulin sensitivity.
- establish whether the beneficial effect of antilipolytic drugs may be attributable at least in part to a decrease in AT inflammation.
Allocation: Randomized, Control: Placebo Control, Endpoint Classification: Pharmacodynamics Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Basic Science
training, nicotinic acid, Placebo
Centre d'Investigation Clinique, Purpan University Toulouse Hospital
University Hospital, Toulouse
Published on BioPortfolio: 2014-08-27T03:15:23-0400
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