title: Trimetazidine reduces endogenous free fatty acid oxidation and improves myocardial efficiency in obese humans.
abstract: BACKGROUND
  The metabolic modulator trimetazidine (TMZ) has been suggested to induce a metabolic shift from myocardial fatty acid oxidation (FAO) to glucose utilization, but this mechanism remains unproven in humans. The oxidation of plasma derived FA is commonly measured in humans, whereas the contribution of FA from triglycerides stored in the myocardium has been poorly characterized.
  
  
  OBJECTIVE
  To verify the hypothesis that TMZ induces a metabolic shift, we combined positron emission tomography (PET) and magnetic resonance spectroscopy ((1)H-MRS) to measure myocardial FAO from plasma and intracellular lipids, and myocardial glucose metabolism. Nine obese subjects were studied before and after 1 month of TMZ treatment. Myocardial glucose and FA metabolism were assessed by PET with (18)F-fluorodeoxyglucose and (11)C-palmitate. (1)H-MRS was used to measure myocardial lipids, the latter being integrated into the PET data analysis to quantify myocardial triglyceride turnover.
  
  
  RESULTS
  Myocardial FAO derived from intracellular lipids was at least equal to that of plasma FAs (P = NS). BMI and cardiac work were positively associated with the oxidation of plasma derived FA (P ≤ 0.01). TMZ halved total and triglyceride-derived myocardial FAO (32.7 ± 8.0 to 19.6 ± 4.0 μmol/min and 23.7 ± 7.5 to 10.3 ± 2.7 μmol/min, respectively; P ≤ 0.05). These changes were accompanied by increased cardiac efficiency since unchanged LV work (1.6 ± 0.2 to 1.6 ± 0.1 Watt/g × 10(2), NS) was associated with decreased work energy from the intramyocardial triglyceride oxidation (1.6 ± 0.5 to 0.4 ± 0.1 Watt/g × 10(2), P = 0.036).
  
  
  CONCLUSIONS
  In obese subjects, we demonstrate that myocardial intracellular triglyceride oxidation significantly provides FA-derived energy for mechanical work. TMZ reduced the oxidation of triglyceride-derived myocardial FAs improving myocardial efficiency.
authors: Turku PET Centre, University of Turku, Turku, Finland.
authors: Marco
authors: M
authors: Bucci
authors: Ronald
authors: R
authors: Borra
authors: Kjell
authors: K
authors: Någren
authors: Jussi P
authors: JP
authors: Pärkkä
authors: Silvia
authors: S
authors: Del Ry
authors: Romina
authors: R
authors: Maggio
authors: Helena
authors: H
authors: Tuunanen
authors: Tapio
authors: T
authors: Viljanen
authors: Manuela
authors: M
authors: Cabiati
authors: Sara
authors: S
authors: Rigazio
authors: Markku
authors: M
authors: Taittonen
authors: Uberto
authors: U
authors: Pagotto
authors: Riitta
authors: R
authors: Parkkola
authors: Lionel H
authors: LH
authors: Opie
authors: Pirjo
authors: P
authors: Nuutila
authors: Juhani
authors: J
authors: Knuuti
authors: Patricia
authors: P
authors: Iozzo
mesh_terms: D000328:Adult; D000368:Aged; D015992:Body Mass Index; D005230:Fatty Acids, Nonesterified / Q000378:metabolism*; D005260:Female; D005947:Glucose / Q000378:metabolism; D006334:Heart Function Tests; D006439:Hemodynamics; D006801:Humans; D050356:Lipid Metabolism / Q000187:drug effects; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000188:drug therapy*; D010168:Palmitates / Q000378:metabolism; D049268:Positron-Emission Tomography; D014292:Trimetazidine / Q000494:pharmacology*; D014665:Vasodilator Agents / Q000494:pharmacology*
chemical_list: D005230:Fatty Acids, Nonesterified; D010168:Palmitates; D014665:Vasodilator Agents; D005947:Glucose; D014292:Trimetazidine