title: Contractile function and energy metabolism of skeletal muscle in rats with secondary carnitine deficiency.
abstract: The consequences of carnitine depletion upon metabolic and contractile characteristics of skeletal muscle remain largely unexplored. Therefore, we investigated the effect of N-trimethyl-hydrazine-3-propionate (THP) administration, a carnitine analog inhibiting carnitine biosynthesis and renal reabsorption of carnitine, on skeletal muscle function and energy metabolism. Male Sprague-Dawley rats were fed a standard rat chow in the absence (CON; n = 8) or presence of THP (n = 8) for 3 wk. Following treatment, rats were fasted for 24 h prior to excision of their soleus and EDL muscles for biochemical characterization at rest and following 5 min of contraction in vitro. THP treatment reduced the carnitine pool by ∼80% in both soleus and EDL muscles compared with CON. Carnitine depletion was associated with a 30% decrease soleus muscle weight, whereas contractile function (expressed per gram of muscle), free coenzyme A, and water content remained unaltered from CON. Muscle fiber distribution and fiber area remained unaffected, whereas markers of apoptosis were increased in soleus muscle of THP-treated rats. In EDL muscle, carnitine depletion was associated with reduced free coenzyme A availability (-25%, P < 0.05), impaired peak tension development (-44%, P < 0.05), and increased glycogen hydrolysis (52%, P < 0.05) during muscle contraction, whereas PDC activation, muscle weight, and water content remained unaltered from CON. In conclusion, myopathy associated with carnitine deficiency can have different causes. Although muscle atrophy, most likely due to increased apoptosis, is predominant in muscle composed predominantly of type I fibers (soleus), disturbance of energy metabolism appears to be the major cause in muscle composed of type II fibers (EDL).
authors.affiliation: Division of Clinical Pharmacology and Toxicology, Department of Biomedicine, and.
authors.forename: Paul A
authors.initials: PA
authors.lastname: Roberts
authors.affiliation: Division of Clinical Pharmacology and Toxicology, Department of Biomedicine, and.
authors.forename: Jamal
authors.initials: J
authors.lastname: Bouitbir
authors.affiliation: Division of Clinical Pharmacology and Toxicology, Department of Biomedicine, and.
authors.forename: Annalisa
authors.initials: A
authors.lastname: Bonifacio
authors.affiliation: Division of Clinical Pharmacology and Toxicology, Department of Biomedicine, and.
authors.forename: François
authors.initials: F
authors.lastname: Singh
authors.affiliation: Division of Clinical Pharmacology and Toxicology, Department of Biomedicine, and.
authors.forename: Priska
authors.initials: P
authors.lastname: Kaufmann
authors.affiliation: Department of Biomedicine, and Department of Anesthesia, University Hospital Basel, Basel, Switzerland.
authors.forename: Albert
authors.initials: A
authors.lastname: Urwyler
authors.affiliation: Division of Clinical Pharmacology and Toxicology, Department of Biomedicine, and stephan.kraehenbuehl@usb.ch.
authors.forename: Stephan
authors.initials: S
authors.lastname: Krähenbühl
mesh_terms: D000818:Animals; D017209:Apoptosis; D015415:Biomarkers / Q000378:metabolism; D002331:Carnitine / Q000037:antagonists & inhibitors / Q000172:deficiency*; D003677:Deficiency Diseases / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D004195:Disease Models, Animal; D004734:Energy Metabolism; D050261:Glycogenolysis; D008297:Male; D008763:Methylhydrazines; D009119:Muscle Contraction; D024510:Muscle Development; D018656:Muscle Fibers, Fast-Twitch / Q000378:metabolism / Q000473:pathology; D018657:Muscle Fibers, Slow-Twitch / Q000378:metabolism / Q000473:pathology; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D009133:Muscular Atrophy / Q000209:etiology*; D011897:Random Allocation; D017207:Rats, Sprague-Dawley
chemical_list: D015415:Biomarkers; D008763:Methylhydrazines; C050147:3-(2,2,2-trimethylhydrazine)propionate; D002331:Carnitine
keywords: N-trimethyl-hydrazine-3-propionate; apoptosis; carbohydrate metabolism; muscle atrophy; secondary carnitine deficiency