Abstract
AimsObesity 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.MethodsC57BL/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 HOMAIR, 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.ResultsVehicle-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.ConclusionsOral 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.
Highlights
Obesity is a fast growing problem that is reaching epidemic proportions worldwide, and is associated with an increased risk of premature death [1]
L-carnitine plays an important role in the transport of long-chain fatty acids into the mitochondrial matrix, since it serves as an essential substrate for the enzyme which catalyses the initial step of b-oxidation, carnitine palmitoyltransferase 1
The selected dose of PLC has been previously reported to improve endothelial function in spontaneously hypertensive rats [7,8,9] and to prevent obesity development and insulin resistance in fatty Zucker rats [10]. This dose assures the increase of L-carnitine tissue levels since a similar dose of PLC (180 mg/kg/day) administered in the drinking water during two weeks led to an increase in the cardiac total carnitine content [14]
Summary
Obesity is a fast growing problem that is reaching epidemic proportions worldwide, and is associated with an increased risk of premature death [1]. Propionyl-L-carnitine (PLC) is a short chain fatty acid esterified to carnitine that is rapidly transported into cells, in particular to the mitochondria, where it is transformed into free carnitine and propionyl coenzyme A [4,5]. The latter is converted into succinyl coenzyme A and to succinate, which is involved in the citric acid cycle. L-carnitine plays an important role in the transport of long-chain fatty acids into the mitochondrial matrix, since it serves as an essential substrate for the enzyme which catalyses the initial step of b-oxidation, carnitine palmitoyltransferase 1 Both carnitine and PLC play significant roles in fatty acid oxidation and energy expenditure. Both compounds exert protective effects on vascular endothelium [7,8,9]
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