Oral supplementation of propionyl-l-carnitine reduces body weight and hyperinsulinaemia in obese Zucker rats.
Propionyl-L-carnitine (PLC) is an SCFA esterified to carnitine that plays an important role in fatty acid oxidation and energy expenditure, in addition to having a protective effect on the endothelium. In order to evaluate the effect of PLC on an animal model of obesity, insulin resistance and, consequently, endothelial dysfunction, lean and obese Zucker rats (OZR) received either vehicle- or PLC-supplemented drinking water (200 mg/kg per d) for 20 weeks. Body weight, food intake, systolic blood pressure and heart rate were controlled weekly and an oral glucose tolerance test was performed. Fasting glucose, TAG, cholesterol, HDL, NEFA, adiponectin and insulin were analysed in serum. Visceral adipose tissue and liver were weighed and liver TAG liver composition was evaluated. Endothelial and vascular functions were assessed in the aorta and small mesenteric arteries by response to acetylcholine, sodium nitroprusside and phenylephrine (Phe); NO participation was evaluated after incubation with the NO synthase (NOS) inhibitor NG-nitro-L-arginine methyl ester (L-NAME) and endothelial NOS protein expression by Western blotting. PLC decreased body-weight gain, food intake, adiposity, insulin serum concentration and TAG liver content and improved insulin resistance. Aortae from OZR receiving either vehicle or PLC exhibited a lower contractile response to Phe. PLC-treated OZR showed an enhanced release of endothelial NO upon the adrenergic stimulation. The protection of vascular function found after treatment with PLC in an animal model of insulin resistance supports the necessity of clinical trials showing the effect of L-carnitine supplements on metabolic disorders.
Mingorance
Carmen
C
Departamento de Farmacología, Facultad de Farmacia, Universidad de Sevilla, 41012 Seville, Spain.
Gonzalez del Pozo
Maria
M
Dolores Herrera
Maria
M
Alvarez de Sotomayor
Maria
M
D000818:Animals; D002331:Carnitine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D019587:Dietary Supplements; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004435:Eating / Q000187:drug effects; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology; D005951:Glucose Tolerance Test; D006439:Hemodynamics / Q000187:drug effects; D006946:Hyperinsulinism / Q000178:diet therapy / Q000503:physiopathology; D007333:Insulin Resistance; D008055:Lipids / Q000097:blood; D024821:Metabolic Syndrome / Q000178:diet therapy* / Q000503:physiopathology; D009765:Obesity / Q000178:diet therapy / Q000503:physiopathology; D051381:Rats; D011924:Rats, Zucker; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology; D015430:Weight Gain / Q000187:drug effects
D008055:Lipids; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; C003223:propionylcarnitine; D002331:Carnitine