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Molecular effect of fenofibrate on PBMC gene transcription related to lipid metabolism in patients with metabolic syndrome
Author(s) -
MorenoIndias I.,
Tinahones F.J.,
ClementePostigo M.,
CastellanoCastillo D.,
FernándezGarcía J.C.,
MaciasGonzalez M.,
QueipoOrtuño M.I.,
Cardona F.
Publication year - 2017
Publication title -
clinical endocrinology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.055
H-Index - 147
eISSN - 1365-2265
pISSN - 0300-0664
DOI - 10.1111/cen.13320
Subject(s) - fenofibrate , postprandial , medicine , endocrinology , hypertriglyceridemia , metabolic syndrome , triglyceride , lipid metabolism , fibrate , apolipoprotein b , peroxisome proliferator activated receptor , peripheral blood mononuclear cell , cholesterol , biology , receptor , diabetes mellitus , in vitro , biochemistry
Summary 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 ( PPAR α). 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. Materials and 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 PPAR α and RXR α expression and changes in genes regulated by PPAR α, both baseline and postprandial. Furthermore, in vitro experiments showed that a PPAR α agonist changed the expression of genes related with lipid metabolism. Conclusion Treatment with fenofibrate reduced fasting and postprandial serum triglyceride levels, possibly through a mechanism related with an increase in the expression of RXR α and PPAR α, 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.