title: Propionyl-L-carnitine corrects metabolic and cardiovascular alterations in diet-induced obese mice and improves liver respiratory chain activity.
abstract: OBJECTIVE
  Obesity is a primary contributor to acquired insulin resistance leading to the development of type 2 diabetes and cardiovascular alterations. The carnitine derivate, propionyl-L-carnitine (PLC), plays a key role in energy control. Our aim was to evaluate metabolic and cardiovascular effects of PLC in diet-induced obese mice.
  
  
  METHODS
  C57BL/6 mice were fed a high-fat diet for 9 weeks and then divided into two groups, receiving either free- (vehicle-HF) or PLC-supplemented water (200 mg/kg/day) during 4 additional weeks. Standard diet-fed animals were used as lean controls (vehicle-ST). Body weight and food intake were monitored. Glucose and insulin tolerance tests were assessed, as well as the HOMA(IR), the serum lipid profile, the hepatic and muscular mitochondrial activity and the tissue nitric oxide (NO) liberation. Systolic blood pressure, cardiac and endothelial functions were also evaluated.
  
  
  RESULTS
  Vehicle-HF displayed a greater increase of body weight compared to vehicle-ST that was completely reversed by PLC treatment without affecting food intake. PLC improved the insulin-resistant state and reversed the increased total cholesterol but not the increase in free fatty acid, triglyceride and HDL/LDL ratio induced by high-fat diet. Vehicle-HF exhibited a reduced cardiac output/body weight ratio, endothelial dysfunction and tissue decrease of NO production, all of them being improved by PLC treatment. Finally, the decrease of hepatic mitochondrial activity by high-fat diet was reversed by PLC.
  
  
  CONCLUSIONS
  Oral administration of PLC improves the insulin-resistant state developed by obese animals and decreases the cardiovascular risk associated to this metabolic alteration probably via correction of mitochondrial function.
authors.affiliation: Department of Pharmacology, School of Pharmacy, University of Sevilla, Sevilla, Spain.
authors.forename: Carmen
authors.initials: C
authors.lastname: Mingorance
authors.forename: Lucie
authors.initials: L
authors.lastname: Duluc
authors.forename: Matthieu
authors.initials: M
authors.lastname: Chalopin
authors.forename: Gilles
authors.initials: G
authors.lastname: Simard
authors.forename: Pierre-Henri
authors.initials: PH
authors.lastname: Ducluzeau
authors.forename: Maria Dolores
authors.initials: MD
authors.lastname: Herrera
authors.forename: Maria
authors.initials: M
authors.lastname: Alvarez de Sotomayor
authors.forename: Ramaroson
authors.initials: R
authors.lastname: Andriantsitohaina
mesh_terms: D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002331:Carnitine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004032:Diet; D004579:Electron Transport / Q000187:drug effects*; D005247:Feeding Behavior / Q000187:drug effects; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009929:Organ Size / Q000187:drug effects
chemical_list: C003223:propionylcarnitine; D002331:Carnitine