title: Molecular effect of fenofibrate on PBMC gene transcription related to lipid metabolism in patients with metabolic syndrome.
abstract: BACKGROUND
  Both fasting and postprandial hypertriglyceridaemia are considered independent risk factors for atherosclerosis. Treatment of hypertriglyceridaemia is based on fibrates, which activate the peroxisome proliferator-activated receptor alpha (PPARα). However, the metabolic pathways that activate or inhibit fibrates, and how the postprandial triglyceride levels are modified, have not yet been fully described. Accordingly, the aim of this study was to determine the feasibility of peripheral blood mononuclear cells (PBMC) to study the effects of fenofibrate in patients with the metabolic syndrome.
  
  
  METHODS
  A fat overload was given to 50 patients before and after treatment with fenofibrate for 3 months. Anthropometric and biochemical variables as well as gene expression in PBMC were analysed.
  
  
  RESULTS
  After treatment with fenofibrate, we observed a decrease in both baseline and postprandial (3 h after the fat overload) levels of serum triglycerides, cholesterol and uric acid and an increase in HDL cholesterol and apolipoprotein AI levels. After treatment, there was also a rise in PPARα and RXRα expression and changes in genes regulated by PPARα, both baseline and postprandial. Furthermore, in vitro experiments showed that a PPARα agonist changed the expression of genes related with lipid metabolism.
  
  
  CONCLUSIONS
  Treatment with fenofibrate reduced fasting and postprandial serum triglyceride levels, possibly through a mechanism related with an increase in the expression of RXRα and PPARα, by activating the pathways involved in the uptake and degradation of triglycerides and increasing the synthesis of apolipoprotein. These results suggest that PBMC may be useful for the easy study of fenofibrate actions.
authors.affiliation: CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), CB06/03, Instituto de Salud Carlos III, Madrid, Spain.|Unidad Gestión Clínica Endocrinología y Nutrición, Instituto de Investigación Biomédica de Málaga (IBIMA), Universidad de Málaga, Málaga, Spain.|Hospital Clinico Universitario Virgen de la Victoria, Universidad de Malaga, Malaga, Spain.
authors.forename: I
authors.initials: I
authors.lastname: Moreno-Indias
authors.affiliation: CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), CB06/03, Instituto de Salud Carlos III, Madrid, Spain.|Unidad Gestión Clínica Endocrinología y Nutrición, Instituto de Investigación Biomédica de Málaga (IBIMA), Universidad de Málaga, Málaga, Spain.|Hospital Clinico Universitario Virgen de la Victoria, Universidad de Malaga, Malaga, Spain.
authors.forename: F J
authors.initials: FJ
authors.lastname: Tinahones
authors.affiliation: CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), CB06/03, Instituto de Salud Carlos III, Madrid, Spain.|Unidad Gestión Clínica Endocrinología y Nutrición, Instituto de Investigación Biomédica de Málaga (IBIMA), Universidad de Málaga, Málaga, Spain.|Hospital Clinico Universitario Virgen de la Victoria, Universidad de Malaga, Malaga, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Clemente-Postigo
authors.affiliation: CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), CB06/03, Instituto de Salud Carlos III, Madrid, Spain.|Unidad Gestión Clínica Endocrinología y Nutrición, Instituto de Investigación Biomédica de Málaga (IBIMA), Universidad de Málaga, Málaga, Spain.|Hospital Clinico Universitario Virgen de la Victoria, Universidad de Malaga, Malaga, Spain.
authors.forename: D
authors.initials: D
authors.lastname: Castellano-Castillo
authors.affiliation: CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), CB06/03, Instituto de Salud Carlos III, Madrid, Spain.|Unidad Gestión Clínica Endocrinología y Nutrición, Instituto de Investigación Biomédica de Málaga (IBIMA), Universidad de Málaga, Málaga, Spain.|Hospital Clinico Universitario Virgen de la Victoria, Universidad de Malaga, Malaga, Spain.
authors.forename: J C
authors.initials: JC
authors.lastname: Fernández-García
authors.affiliation: CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), CB06/03, Instituto de Salud Carlos III, Madrid, Spain.|Unidad Gestión Clínica Endocrinología y Nutrición, Instituto de Investigación Biomédica de Málaga (IBIMA), Universidad de Málaga, Málaga, Spain.|Hospital Clinico Universitario Virgen de la Victoria, Universidad de Malaga, Malaga, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Macias-Gonzalez
authors.affiliation: CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), CB06/03, Instituto de Salud Carlos III, Madrid, Spain.|Unidad Gestión Clínica Endocrinología y Nutrición, Instituto de Investigación Biomédica de Málaga (IBIMA), Universidad de Málaga, Málaga, Spain.|Hospital Clinico Universitario Virgen de la Victoria, Universidad de Malaga, Malaga, Spain.
authors.forename: M I
authors.initials: MI
authors.lastname: Queipo-Ortuño
authors.affiliation: CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), CB06/03, Instituto de Salud Carlos III, Madrid, Spain.|Unidad Gestión Clínica Endocrinología y Nutrición, Instituto de Investigación Biomédica de Málaga (IBIMA), Universidad de Málaga, Málaga, Spain.|Hospital Clinico Universitario Virgen de la Victoria, Universidad de Malaga, Malaga, Spain.
authors.forename: F
authors.identifier: http://orcid.org/0000-0003-4460-6824
authors.initials: F
authors.lastname: Cardona
mesh_terms: D000328:Adult; D001053:Apolipoproteins / Q000096:biosynthesis; D005260:Female; D011345:Fenofibrate / Q000494:pharmacology*; D006801:Humans; D000960:Hypolipidemic Agents / Q000494:pharmacology; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D050356:Lipid Metabolism / Q000235:genetics*; D008297:Male; D024821:Metabolic Syndrome / Q000188:drug therapy / Q000378:metabolism*; D008875:Middle Aged; D047493:PPAR alpha / Q000378:metabolism; D047490:Retinoid X Receptor alpha / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects*; D014280:Triglycerides / Q000097:blood
chemical_list: D001053:Apolipoproteins; D000960:Hypolipidemic Agents; D047493:PPAR alpha; D047490:Retinoid X Receptor alpha; D014280:Triglycerides; D011345:Fenofibrate