title: Influence of fenofibrate treatment on triacylglycerides, diacylglycerides and fatty acids in fructose fed rats.
abstract: Fenofibrate (FF) lowers plasma triglycerides via PPARα activation. Here, we analyzed lipidomic changes upon FF treatment of fructose fed rats. Three groups with 6 animals each were defined as control, fructose-fed and fructose-fed/FF treated. Male Wistar Unilever Rats were subjected to 10% fructose-feeding for 20 days. On day 14, fenofibrate treatment (100 mg/kg p.o.) was initiated and maintained for 7 days. Lipid species in serum were analyzed using mass spectrometry (ESI-MS/MS; LC-FT-MS, GC-MS) on days 0, 14 and 20 in all three groups. In addition, lipid levels in liver and intestine were determined. Short-chain TAGs increased in serum and liver upon fructose-feeding, while almost all TAG-species decreased under FF treatment. Long-chain unsaturated DAG-levels (36:1, 36:2, 36:4, 38:3, 38:4, 38:5) increased upon FF treatment in rat liver and decreased in rat serum. FAs, especially short-chain FAs (12:0, 14:0, 16:0) increased during fructose-challenge. VLDL secretion increased upon fructose-feeding and together with FA-levels decreased to control levels during FF treatment. Fructose challenge of de novo fatty acid synthesis through fatty acid synthase (FAS) may enhance the release of FAs ≤ 16:0 chain length, a process reversed by FF-mediated PPARα-activation.
authors.affiliation: Institute for Clinical Chemistry and Laboratory Medicine, University Hospital Regensburg, Regensburg, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Kopf
authors.affiliation: Sanofi-Aventis Germany, R&D DIAB Div./Biomarker & Diagnostics, Frankfurt, Germany.
authors.forename: Hans-Ludwig
authors.initials: HL
authors.lastname: Schaefer
authors.affiliation: Core Facility Mass Spectrometry, ZMF, Medical University Graz, Graz, Austria.
authors.forename: Martin
authors.initials: M
authors.lastname: Troetzmueller
authors.affiliation: Core Facility Mass Spectrometry, ZMF, Medical University Graz, Graz, Austria.
authors.forename: Harald
authors.initials: H
authors.lastname: Koefeler
authors.affiliation: Sanofi-Aventis Germany, R&D DIAB Div./Biomarker & Diagnostics, Frankfurt, Germany.
authors.forename: Mark
authors.initials: M
authors.lastname: Broenstrup
authors.affiliation: Institute for Clinical Chemistry and Laboratory Medicine, University Hospital Regensburg, Regensburg, Germany.
authors.forename: Tatiana
authors.initials: T
authors.lastname: Konovalova
authors.affiliation: Institute for Clinical Chemistry and Laboratory Medicine, University Hospital Regensburg, Regensburg, Germany.
authors.forename: Gerd
authors.initials: G
authors.lastname: Schmitz
mesh_terms: D000818:Animals; D004075:Diglycerides / Q000097:blood*; D005227:Fatty Acids / Q000097:blood*; D011345:Fenofibrate / Q000008:administration & dosage*; D005632:Fructose / Q000008:administration & dosage*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D014280:Triglycerides / Q000097:blood*
chemical_list: D004075:Diglycerides; D005227:Fatty Acids; D014280:Triglycerides; D005632:Fructose; D011345:Fenofibrate