Publications (2)7.96 Total impact
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Article: Increased intramyocellular lipids but unaltered in vivo mitochondrial oxidative phosphorylation in skeletal muscle of adipose triglyceride lipase-deficient mice.
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ABSTRACT: Adipose triglyceride lipase (ATGL) is a lipolytic enzyme that is highly specific for triglyceride hydrolysis. The ATGL-knockout mouse (ATGL(-/-)) accumulates lipid droplets in various tissues, including skeletal muscle, and has poor maximal running velocity and endurance capacity. In this study, we tested whether abnormal lipid accumulation in skeletal muscle impairs mitochondrial oxidative phosphorylation, and hence, explains the poor muscle performance of ATGL(-/-) mice. In vivo ¹H magnetic resonance spectroscopy of the tibialis anterior of ATGL(-/-) mice revealed that its intramyocellular lipid pool is approximately sixfold higher than in WT controls (P = 0.0007). In skeletal muscle of ATGL(-/-) mice, glycogen content was decreased by 30% (P < 0.05). In vivo ³¹P magnetic resonance spectra of resting muscles showed that WT and ATGL(-/-) mice have a similar energy status: [PCr], [P(i)], PCr/ATP ratio, PCr/P(i) ratio, and intracellular pH. Electrostimulated muscles from WT and ATGL(-/-) mice showed the same PCr depletion and pH reduction. Moreover, the monoexponential fitting of the PCr recovery curve yielded similar PCr recovery times (τPCr; 54.1 ± 6.1 s for the ATGL(-/-) and 58.1 ± 5.8 s for the WT), which means that overall muscular mitochondrial oxidative capacity was comparable between the genotypes. Despite similar in vivo mitochondrial oxidative capacities, the electrostimulated muscles from ATGL(-/-) mice displayed significantly lower force production and increased muscle relaxation time than the WT. These findings suggest that mechanisms other than mitochondrial dysfunction cause the impaired muscle performance of ATGL(-/-) mice.AJP Endocrinology and Metabolism 04/2012; 303(1):E71-81. · 4.75 Impact Factor -
Article: Gated dynamic 31P MRS shows reduced contractile phosphocreatine breakdown in mice deficient in cytosolic creatine kinase and adenylate kinase.
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ABSTRACT: We developed a new dedicated measurement protocol for dynamic (31)P MRS analysis in contracting calf muscles of the mouse, using minimally invasive assessment of the contractile force combined with the acquisition of spectroscopic data gated to muscle contraction and determination of phosphocreatine (PCr) recovery rate and ATP contractile cost. This protocol was applied in a comparative study of six wild type (WT) mice and six mice deficient in cytosolic creatine kinase and adenylate kinase isoform 1 (MAK(-/-) mice) using 70 repeated tetanic contractions at two contractions per minute. Force levels during single contractions, and metabolite levels and tissue pH during resting conditions were similar in muscles of MAK(-/-) and WT mice. Strikingly, muscle relaxation after contraction was significantly delayed in MAK(-/-) mice, but during repeated contractions, the decrease in the force was similar in both mouse types. Gated data acquisition showed a negligible PCr breakdown in MAK(-/-) immediately after contraction, without a concomitant decrease in ATP or tissue pH. This protocol enabled the determination of rapid PCr changes that would otherwise go unnoticed due to intrinsic low signal-to-noise ratio (SNR) in mouse skeletal muscles combined with an assessment of the PCr recovery rate. Our results suggest that MAK(-/-) mice use alternative energy sources to maintain force during repeated contractions when PCr breakdown is reduced. Furthermore, the absence of large increases in adenosine diphosphate (ADP) or differences in force compared to WT mice in our low-intensity protocol indicate that creatine kinase (CK) and adenylate kinase (AK) are especially important in facilitating energy metabolism during very high energy demands.NMR in Biomedicine 01/2009; 22(5):523-31. · 3.21 Impact Factor
