title: Imaging mass spectrometry reveals fiber-specific distribution of acetylcarnitine and contraction-induced carnitine dynamics in rat skeletal muscles.
abstract: Carnitine is well recognized as a key regulator of long-chain fatty acyl group translocation into the mitochondria. In addition, carnitine, as acetylcarnitine, acts as an acceptor of excess acetyl-CoA, a potent inhibitor of pyruvate dehydrogenase. Here, we provide a new methodology for accurate quantification of acetylcarnitine content and determination of its localization in skeletal muscles. We used matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI-IMS) to visualize acetylcarnitine distribution in rat skeletal muscles. MALDI-IMS and immunohistochemistry of serial cross-sections showed that acetylcarnitine was enriched in the slow-type muscle fibers. The concentration of ATP was lower in muscle regions with abundant acetylcarnitine, suggesting a relationship between acetylcarnitine and metabolic activity. Using our novel method, we detected an increase in acetylcarnitine content after muscle contraction. Importantly, this increase was not detected using traditional biochemical assays of homogenized muscles. We also demonstrated that acetylation of carnitine during muscle contraction was concomitant with glycogen depletion. Our methodology would be useful for the quantification of acetylcarnitine and its contraction-induced kinetics in skeletal muscles.
authors.affiliation: Department of Health Promotion Sciences, Graduate School of Human Health Sciences, Tokyo Metropolitan University, Tokyo, Japan.
authors.forename: Yasuro
authors.initials: Y
authors.lastname: Furuichi
authors.affiliation: Department of Health Promotion Sciences, Graduate School of Human Health Sciences, Tokyo Metropolitan University, Tokyo, Japan; Department of Cell Biology and Anatomy, Hamamatsu University School of Medicine, Hamamatsu, Japan. Electronic address: naokog@tmu.ac.jp.
authors.forename: Naoko
authors.initials: N
authors.lastname: Goto-Inoue
authors.affiliation: Department of Health Promotion Sciences, Graduate School of Human Health Sciences, Tokyo Metropolitan University, Tokyo, Japan.
authors.forename: Yasuko
authors.initials: Y
authors.lastname: Manabe
authors.affiliation: Department of Cell Biology and Anatomy, Hamamatsu University School of Medicine, Hamamatsu, Japan.
authors.forename: Mitsutoshi
authors.initials: M
authors.lastname: Setou
authors.affiliation: Faculty of Human Sciences, Kanazawa University, Kanazawa, Japan.
authors.forename: Kazumi
authors.initials: K
authors.lastname: Masuda
authors.affiliation: Department of Health Promotion Sciences, Graduate School of Human Health Sciences, Tokyo Metropolitan University, Tokyo, Japan. Electronic address: fujiin@tmu.ac.jp.
authors.forename: Nobuharu L
authors.initials: NL
authors.lastname: Fujii
mesh_terms: D000108:Acetylcarnitine / Q000378:metabolism*; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002331:Carnitine / Q000378:metabolism*; D008297:Male; D009119:Muscle Contraction; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D053719:Tandem Mass Spectrometry
chemical_list: D000108:Acetylcarnitine; D000255:Adenosine Triphosphate; D002331:Carnitine
keywords: Carnitine; Fiber type; Muscle contraction