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Contractile function and energy metabolism of skeletal muscle in rats with secondary carnitine deficiency

Roberts, Paul A. and Bouitbir, Jamal and Bonifacio, Annalisa and Singh, François and Kaufmann, Priska and Urwyler, Albert and Krähenbühl, Stephan. (2015) Contractile function and energy metabolism of skeletal muscle in rats with secondary carnitine deficiency. American Journal of Physiology. Endocrinology and Metabolism, 309 (3). E265-E274.

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Official URL: http://edoc.unibas.ch/41411/

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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).
Faculties and Departments:03 Faculty of Medicine > Bereich Medizinische Fächer (Klinik) > Klinische Pharmakologie > Klinische Pharmakologie (Krähenbühl)
03 Faculty of Medicine > Departement Klinische Forschung > Bereich Medizinische Fächer (Klinik) > Klinische Pharmakologie > Klinische Pharmakologie (Krähenbühl)
05 Faculty of Science > Departement Pharmazeutische Wissenschaften > Ehemalige Einheiten Pharmazie > Pharmakologie (Krähenbühl)
05 Faculty of Science > Departement Pharmazeutische Wissenschaften
UniBasel Contributors:Krähenbühl, Stephan and Bouitbir, Jamal and Singh, François and Urwyler, Albert
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:American Physiological Society
ISSN:0193-1849
e-ISSN:1522-1555
Note:Publication type according to Uni Basel Research Database: Journal article
Identification Number:
Last Modified:26 Aug 2020 14:34
Deposited On:25 Aug 2016 09:03

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