The Experts below are selected from a list of 195 Experts worldwide ranked by ideXlab platform
Antonella Gorini - One of the best experts on this subject based on the ideXlab platform.
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Functional proteomics of synaptic plasma membrane ATP-ases of rat hippocampus: Effect of l-Acetylcarnitine and relationships with Dementia and Depression pathophysiology
European journal of pharmacology, 2015Co-Authors: Federica Ferrari, Antonella Gorini, Roberto Federico VillaAbstract:Abstract Synaptic energy state and mitochondrial dysfunction are crucial factors in many brain pathologies. l -Acetylcarnitine, a natural derivative of carnitine, improves brain energy metabolism, and has been proposed for the Therapy of many neurological and psychiatric diseases. The effects of the drug on the maximum rate (Vmax) of enzymatic activities related to hippocampal synaptic energy utilization were evaluated, in the perspective of its employment for Dementias and Depression Therapy. Two types of synaptic plasma membranes (SPM1 and SPM2) were isolated from the hippocampus of rats treated with l -Acetylcarnitine (30 and 60 mg/kg i.p., 28 days, 5 days/week). Acetylcholinesterase (AChE); Na+, K+, Mg2+-ATP-ase; ouabain-insensitive Mg2+-ATP-ase; Na+, K+-ATP-ase; Ca2+, Mg2+-ATP-ase activities were evaluated. In control animals, enzymatic activities were differently expressed in SPM1 , being the evaluated enzymatic activities higher in SPM2. Subchronic treatment with l -Acetylcarnitine (i) did not modify AChE on both SPMs; (ii) increased Na+, K+, Mg2+-ATP-ase, ouabain-insensitive Mg2+-ATP-ase and Na+, K+-ATP-ase at the dose of 30 and 60 mg/kg on SPM1 and SPM2; (iii) increased Ca2+, Mg2+-ATP-ase activity on both SPMs at the dose of 60 mg/kg. These results have been discussed considering the pathophysiology and treatment of Dementias and Depression because, although referred to normal healthy animals, they support the notion that l -Acetylcarnitine may have positive effects in these pathologies.
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Action of L-Acetylcarnitine on Different Cerebral Mitochondrial Populations from Cerebral Cortex
Neurochemical research, 1998Co-Authors: Antonella Gorini, Angela D'angelo, Roberto Federico VillaAbstract:The maximum rate (Vmax) of some mitochondrial enzymatic activities related to the energy transduction (citrate synthase, α-ketoglutarate dehydrogenase, succinate dehydrogenase, malate dehydrogenase, cytochrome oxidase) and amino acid metabolism (glutamate dehydrogenase, glutamate-pyruvate-transaminase, glutamate-oxaloacetate-transaminase) was evaluated in non-synaptic (free) and intra-synaptic mitochondria from rat brain cerebral cortex. Three types of mitochondria were isolated from rats subjected to i.p. treatment with L-Acetylcarnitine at two different doses (30 and 60 mg·kg−1, 28 days, 5 days/week). In control (vehicle-treated) animals, enzyme activities are differently expressed in non-synaptic mitochondria respect to intra-synaptic “light” and “heavy” ones. In fact, α-ketoglutarate dehydrogenase, succinate dehydrogenase, malate dehydrogenase, glutamate-pyruvate-transaminase and glutamate-oxaloacetate-transaminase are lower, while citrate synthase, cytochrome oxidase and glutamate dehydrogenase are higher in intra-synaptic mitochondria than in non-synaptic ones. This confirms that in various types of brain mitochondria a different metabolic machinery exists, due to their location in vivo. Treatment with L-Acetylcarnitine decreased citrate synthase and glutamate dehydrogenase activities, while increased cytochrome oxidase and α-ketoglutarate dehydrogenase activities only in intra-synaptic mitochondria. Therefore in vivo administration of L-Acetylcarnitine mainly affects some specific enzyme activities, suggesting a specific molecular trigger mode of action and only of the intra-synaptic mitochondria, suggesting a specific subcellular trigger site of action.
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Acetylcholinesterase Activity of Synaptic Plasma Membranes during Ageing: Effect of L-Acetylcarnitine
Dementia (Basel Switzerland), 1996Co-Authors: Antonella Gorini, B. Ghigini, R.f. VillaAbstract:A physiopathological role for acetylcholine (ACh) was hypothesized during ageing and related neurodegenerative diseases, e.g. dementia. This research was aimed to study acetylcholinesterase (AChE) activity during development and ageing of the frontal cerebral cortex of 4-, 8-, 12-, 16-, 20- and 24-month-old rats. This study was performed on synaptic plasma membranes, the specific subcellular compartment where the enzyme is located in vivo both in control animals and after in vivo acute treatment with L-Acetylcarnitine. Maximum AChE activity was unaffected by age, and L-Acetylcarnitine treatment increased enzyme activity in synaptic plasma membranes of 8-month-old rats. A comprehensive analysis of these results suggests: (a) the observed alterations in protein can substantially affect neurochemical data if results are presented as specific activities per unit protein; (b) energy metabolism plays the major role in the disturbed ACh metabolism during ageing and (c) the understanding of the mode of action of L-Acetylcarnitine in treatment of dementia.
Roberto Federico Villa - One of the best experts on this subject based on the ideXlab platform.
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Functional proteomics of synaptic plasma membrane ATP-ases of rat hippocampus: Effect of l-Acetylcarnitine and relationships with Dementia and Depression pathophysiology
European journal of pharmacology, 2015Co-Authors: Federica Ferrari, Antonella Gorini, Roberto Federico VillaAbstract:Abstract Synaptic energy state and mitochondrial dysfunction are crucial factors in many brain pathologies. l -Acetylcarnitine, a natural derivative of carnitine, improves brain energy metabolism, and has been proposed for the Therapy of many neurological and psychiatric diseases. The effects of the drug on the maximum rate (Vmax) of enzymatic activities related to hippocampal synaptic energy utilization were evaluated, in the perspective of its employment for Dementias and Depression Therapy. Two types of synaptic plasma membranes (SPM1 and SPM2) were isolated from the hippocampus of rats treated with l -Acetylcarnitine (30 and 60 mg/kg i.p., 28 days, 5 days/week). Acetylcholinesterase (AChE); Na+, K+, Mg2+-ATP-ase; ouabain-insensitive Mg2+-ATP-ase; Na+, K+-ATP-ase; Ca2+, Mg2+-ATP-ase activities were evaluated. In control animals, enzymatic activities were differently expressed in SPM1 , being the evaluated enzymatic activities higher in SPM2. Subchronic treatment with l -Acetylcarnitine (i) did not modify AChE on both SPMs; (ii) increased Na+, K+, Mg2+-ATP-ase, ouabain-insensitive Mg2+-ATP-ase and Na+, K+-ATP-ase at the dose of 30 and 60 mg/kg on SPM1 and SPM2; (iii) increased Ca2+, Mg2+-ATP-ase activity on both SPMs at the dose of 60 mg/kg. These results have been discussed considering the pathophysiology and treatment of Dementias and Depression because, although referred to normal healthy animals, they support the notion that l -Acetylcarnitine may have positive effects in these pathologies.
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Action of L-Acetylcarnitine on Different Cerebral Mitochondrial Populations from Cerebral Cortex
Neurochemical research, 1998Co-Authors: Antonella Gorini, Angela D'angelo, Roberto Federico VillaAbstract:The maximum rate (Vmax) of some mitochondrial enzymatic activities related to the energy transduction (citrate synthase, α-ketoglutarate dehydrogenase, succinate dehydrogenase, malate dehydrogenase, cytochrome oxidase) and amino acid metabolism (glutamate dehydrogenase, glutamate-pyruvate-transaminase, glutamate-oxaloacetate-transaminase) was evaluated in non-synaptic (free) and intra-synaptic mitochondria from rat brain cerebral cortex. Three types of mitochondria were isolated from rats subjected to i.p. treatment with L-Acetylcarnitine at two different doses (30 and 60 mg·kg−1, 28 days, 5 days/week). In control (vehicle-treated) animals, enzyme activities are differently expressed in non-synaptic mitochondria respect to intra-synaptic “light” and “heavy” ones. In fact, α-ketoglutarate dehydrogenase, succinate dehydrogenase, malate dehydrogenase, glutamate-pyruvate-transaminase and glutamate-oxaloacetate-transaminase are lower, while citrate synthase, cytochrome oxidase and glutamate dehydrogenase are higher in intra-synaptic mitochondria than in non-synaptic ones. This confirms that in various types of brain mitochondria a different metabolic machinery exists, due to their location in vivo. Treatment with L-Acetylcarnitine decreased citrate synthase and glutamate dehydrogenase activities, while increased cytochrome oxidase and α-ketoglutarate dehydrogenase activities only in intra-synaptic mitochondria. Therefore in vivo administration of L-Acetylcarnitine mainly affects some specific enzyme activities, suggesting a specific molecular trigger mode of action and only of the intra-synaptic mitochondria, suggesting a specific subcellular trigger site of action.
Lucas Lindeboom - One of the best experts on this subject based on the ideXlab platform.
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Carnitine supplementation improves metabolic flexibility and skeletal muscle Acetylcarnitine formation in volunteers with impaired glucose tolerance: A randomised controlled trial.
EBioMedicine, 2019Co-Authors: Yvonne M. H. Bruls, Lucas Lindeboom, Esther Phielix, Matthijs K. C. Hesselink, Joachim E. Wildberger, Marlies De Ligt, Bas Havekes, Gert Schaart, Esther Kornips, Deborah M. MuoioAbstract:Abstract Background Type 2 diabetes patients and individuals at risk of developing diabetes are characterized by metabolic inflexibility and disturbed glucose homeostasis. Low carnitine availability may contribute to metabolic inflexibility and impaired glucose tolerance. Here, we investigated whether carnitine supplementation improves metabolic flexibility and insulin sensitivity in impaired glucose tolerant (IGT) volunteers. Methods Eleven IGT- volunteers followed a 36-day placebo- and L -carnitine treatment (2 g/day) in a randomised, placebo-controlled, double blind crossover design. A hyperinsulinemic-euglycemic clamp (40 mU/m2/min), combined with indirect calorimetry (ventilated hood) was performed to determine insulin sensitivity and metabolic flexibility. Furthermore, metabolic flexibility was assessed in response to a high-energy meal. Skeletal muscle Acetylcarnitine concentrations were measured in vivo using long echo time proton magnetic resonance spectroscopy (1H-MRS, TE=500 ms) in the resting state (7:00AM and 5:00PM) and after a 30-min cycling exercise. Twelve normal glucose tolerant (NGT) volunteers were included without any intervention as control group. Results Metabolic flexibility of IGT-subjects completely restored towards NGT control values upon carnitine supplementation, measured during a hyperinsulinemic-euglycemic clamp and meal test. In muscle, carnitine supplementation enhanced the increase in resting Acetylcarnitine concentrations over the day (delta 7:00 AM versus 5:00 PM) in IGT-subjects. Furthermore, carnitine supplementation increased post-exercise Acetylcarnitine concentrations and reduced long-chain acylcarnitine species in IGT-subjects, suggesting the stimulation of a more complete fat oxidation in muscle. Whole-body insulin sensitivity was not affected. Conclusion Carnitine supplementation improves Acetylcarnitine formation and rescues metabolic flexibility in IGT-subjects. Future research should investigate the potential of carnitine in prevention/treatment of type 2 diabetes.
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Longitudinal relaxation time editing for Acetylcarnitine detection with 1 H-MRS.
Magnetic resonance in medicine, 2016Co-Authors: Lucas Lindeboom, Matthijs K. C. Hesselink, Joachim E. Wildberger, Yvonne M. H. Bruls, Petronella A. Van Ewijk, Patrick Schrauwen, Vera B. Schrauwen-hinderlingAbstract:PURPOSE Acetylcarnitine formation is suggested to be crucial in sustaining metabolic flexibility and glucose homeostasis. Recently, we introduced a method to detect Acetylcarnitine in vivo with long TE 1 H-MRS. Differences in T1 relaxation time between lipids and Acetylcarnitine can be exploited for additional lipid suppression in subjects with high myocellular lipid levels. METHODS Acquisition of spectra with an inversion recovery sequence was alternated with standard signal acquisition to suppress short T1 metabolite signals. A proof of principle experiment was conducted in a lean subject and the new approach was subsequently tested in four overweight/obese subjects. RESULTS Using the new T1 editing approach, lipid signals in spectra of skeletal muscle can be (additionally) suppressed by a factor of 10 using a TI of 900 ms. Combination of the long TE protocol with the T1 editing resulted in a well-resolved Acetylcarnitine peak in the obese subjects. CONCLUSION The T1 editing approach suppresses short T1 metabolites and offers a new contrast in 1 H-MRS. The approach should be used in combination with a long TE in subjects with high lipid contamination for accurate quantification of the Acetylcarnitine concentration. Magn Reson Med 77:505-510, 2017. © 2016 International Society for Magnetic Resonance in Medicine.
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long echo time mr spectroscopy for skeletal muscle Acetylcarnitine detection
Journal of Clinical Investigation, 2014Co-Authors: Lucas Lindeboom, Christine I. H. C. Nabuurs, Joris Hoeks, Bram Brouwers, Esther Phielix, Matthijs K. C. Hesselink, Joachim E. Wildberger, Robert Stevens, Eline M Kooi, Timothy R. KovesAbstract:1 H-MRS) to measure skeletal muscle Acetylcarnitine concentrations on a clinical 3T scanner. We applied long-TE 1 H-MRS to measure Acetylcarnitine in endurance- trained athletes, lean and obese sedentary subjects, and type 2 diabetes mellitus (T2DM) patients to cover a wide spectrum in insulin sensitivity. A long-TE 1 H-MRS protocol was implemented for successful detection of skeletal muscle Acetylcarnitine in these individuals. There were pronounced differences in insulin sensitivity, as measured by hyperinsulinemic-euglycemic clamp, and skeletal muscle mitochondrial function, as measured by phosphorus-MRS ( 31 P-MRS), across groups. Insulin sensitivity and mitochondrial function were highest in trained athletes and lowest in T2DM patients. Skeletal muscle Acetylcarnitine concentration showed a reciprocal distribution, with mean Acetylcarnitine concentration correlating with mean insulin sensitivity in each group. These results demonstrate that measuring Acetylcarnitine concentrations with 1 H-MRS is feasible on clinical MR scanners and support the hypothesis that T2DM patients are characterized by a decreased formation of Acetylcarnitine, possibly underlying decreased insulin sensitivity.
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Long–echo time MR spectroscopy for skeletal muscle Acetylcarnitine detection
The Journal of clinical investigation, 2014Co-Authors: Lucas Lindeboom, Christine I. H. C. Nabuurs, Joris Hoeks, Bram Brouwers, Esther Phielix, M. Eline Kooi, Matthijs K. C. Hesselink, Joachim E. Wildberger, Robert Stevens, Timothy R. KovesAbstract:1 H-MRS) to measure skeletal muscle Acetylcarnitine concentrations on a clinical 3T scanner. We applied long-TE 1 H-MRS to measure Acetylcarnitine in endurance- trained athletes, lean and obese sedentary subjects, and type 2 diabetes mellitus (T2DM) patients to cover a wide spectrum in insulin sensitivity. A long-TE 1 H-MRS protocol was implemented for successful detection of skeletal muscle Acetylcarnitine in these individuals. There were pronounced differences in insulin sensitivity, as measured by hyperinsulinemic-euglycemic clamp, and skeletal muscle mitochondrial function, as measured by phosphorus-MRS ( 31 P-MRS), across groups. Insulin sensitivity and mitochondrial function were highest in trained athletes and lowest in T2DM patients. Skeletal muscle Acetylcarnitine concentration showed a reciprocal distribution, with mean Acetylcarnitine concentration correlating with mean insulin sensitivity in each group. These results demonstrate that measuring Acetylcarnitine concentrations with 1 H-MRS is feasible on clinical MR scanners and support the hypothesis that T2DM patients are characterized by a decreased formation of Acetylcarnitine, possibly underlying decreased insulin sensitivity.
Matthijs K. C. Hesselink - One of the best experts on this subject based on the ideXlab platform.
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Carnitine supplementation improves metabolic flexibility and skeletal muscle Acetylcarnitine formation in volunteers with impaired glucose tolerance: A randomised controlled trial.
EBioMedicine, 2019Co-Authors: Yvonne M. H. Bruls, Lucas Lindeboom, Esther Phielix, Matthijs K. C. Hesselink, Joachim E. Wildberger, Marlies De Ligt, Bas Havekes, Gert Schaart, Esther Kornips, Deborah M. MuoioAbstract:Abstract Background Type 2 diabetes patients and individuals at risk of developing diabetes are characterized by metabolic inflexibility and disturbed glucose homeostasis. Low carnitine availability may contribute to metabolic inflexibility and impaired glucose tolerance. Here, we investigated whether carnitine supplementation improves metabolic flexibility and insulin sensitivity in impaired glucose tolerant (IGT) volunteers. Methods Eleven IGT- volunteers followed a 36-day placebo- and L -carnitine treatment (2 g/day) in a randomised, placebo-controlled, double blind crossover design. A hyperinsulinemic-euglycemic clamp (40 mU/m2/min), combined with indirect calorimetry (ventilated hood) was performed to determine insulin sensitivity and metabolic flexibility. Furthermore, metabolic flexibility was assessed in response to a high-energy meal. Skeletal muscle Acetylcarnitine concentrations were measured in vivo using long echo time proton magnetic resonance spectroscopy (1H-MRS, TE=500 ms) in the resting state (7:00AM and 5:00PM) and after a 30-min cycling exercise. Twelve normal glucose tolerant (NGT) volunteers were included without any intervention as control group. Results Metabolic flexibility of IGT-subjects completely restored towards NGT control values upon carnitine supplementation, measured during a hyperinsulinemic-euglycemic clamp and meal test. In muscle, carnitine supplementation enhanced the increase in resting Acetylcarnitine concentrations over the day (delta 7:00 AM versus 5:00 PM) in IGT-subjects. Furthermore, carnitine supplementation increased post-exercise Acetylcarnitine concentrations and reduced long-chain acylcarnitine species in IGT-subjects, suggesting the stimulation of a more complete fat oxidation in muscle. Whole-body insulin sensitivity was not affected. Conclusion Carnitine supplementation improves Acetylcarnitine formation and rescues metabolic flexibility in IGT-subjects. Future research should investigate the potential of carnitine in prevention/treatment of type 2 diabetes.
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Longitudinal relaxation time editing for Acetylcarnitine detection with 1 H-MRS.
Magnetic resonance in medicine, 2016Co-Authors: Lucas Lindeboom, Matthijs K. C. Hesselink, Joachim E. Wildberger, Yvonne M. H. Bruls, Petronella A. Van Ewijk, Patrick Schrauwen, Vera B. Schrauwen-hinderlingAbstract:PURPOSE Acetylcarnitine formation is suggested to be crucial in sustaining metabolic flexibility and glucose homeostasis. Recently, we introduced a method to detect Acetylcarnitine in vivo with long TE 1 H-MRS. Differences in T1 relaxation time between lipids and Acetylcarnitine can be exploited for additional lipid suppression in subjects with high myocellular lipid levels. METHODS Acquisition of spectra with an inversion recovery sequence was alternated with standard signal acquisition to suppress short T1 metabolite signals. A proof of principle experiment was conducted in a lean subject and the new approach was subsequently tested in four overweight/obese subjects. RESULTS Using the new T1 editing approach, lipid signals in spectra of skeletal muscle can be (additionally) suppressed by a factor of 10 using a TI of 900 ms. Combination of the long TE protocol with the T1 editing resulted in a well-resolved Acetylcarnitine peak in the obese subjects. CONCLUSION The T1 editing approach suppresses short T1 metabolites and offers a new contrast in 1 H-MRS. The approach should be used in combination with a long TE in subjects with high lipid contamination for accurate quantification of the Acetylcarnitine concentration. Magn Reson Med 77:505-510, 2017. © 2016 International Society for Magnetic Resonance in Medicine.
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long echo time mr spectroscopy for skeletal muscle Acetylcarnitine detection
Journal of Clinical Investigation, 2014Co-Authors: Lucas Lindeboom, Christine I. H. C. Nabuurs, Joris Hoeks, Bram Brouwers, Esther Phielix, Matthijs K. C. Hesselink, Joachim E. Wildberger, Robert Stevens, Eline M Kooi, Timothy R. KovesAbstract:1 H-MRS) to measure skeletal muscle Acetylcarnitine concentrations on a clinical 3T scanner. We applied long-TE 1 H-MRS to measure Acetylcarnitine in endurance- trained athletes, lean and obese sedentary subjects, and type 2 diabetes mellitus (T2DM) patients to cover a wide spectrum in insulin sensitivity. A long-TE 1 H-MRS protocol was implemented for successful detection of skeletal muscle Acetylcarnitine in these individuals. There were pronounced differences in insulin sensitivity, as measured by hyperinsulinemic-euglycemic clamp, and skeletal muscle mitochondrial function, as measured by phosphorus-MRS ( 31 P-MRS), across groups. Insulin sensitivity and mitochondrial function were highest in trained athletes and lowest in T2DM patients. Skeletal muscle Acetylcarnitine concentration showed a reciprocal distribution, with mean Acetylcarnitine concentration correlating with mean insulin sensitivity in each group. These results demonstrate that measuring Acetylcarnitine concentrations with 1 H-MRS is feasible on clinical MR scanners and support the hypothesis that T2DM patients are characterized by a decreased formation of Acetylcarnitine, possibly underlying decreased insulin sensitivity.
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Long–echo time MR spectroscopy for skeletal muscle Acetylcarnitine detection
The Journal of clinical investigation, 2014Co-Authors: Lucas Lindeboom, Christine I. H. C. Nabuurs, Joris Hoeks, Bram Brouwers, Esther Phielix, M. Eline Kooi, Matthijs K. C. Hesselink, Joachim E. Wildberger, Robert Stevens, Timothy R. KovesAbstract:1 H-MRS) to measure skeletal muscle Acetylcarnitine concentrations on a clinical 3T scanner. We applied long-TE 1 H-MRS to measure Acetylcarnitine in endurance- trained athletes, lean and obese sedentary subjects, and type 2 diabetes mellitus (T2DM) patients to cover a wide spectrum in insulin sensitivity. A long-TE 1 H-MRS protocol was implemented for successful detection of skeletal muscle Acetylcarnitine in these individuals. There were pronounced differences in insulin sensitivity, as measured by hyperinsulinemic-euglycemic clamp, and skeletal muscle mitochondrial function, as measured by phosphorus-MRS ( 31 P-MRS), across groups. Insulin sensitivity and mitochondrial function were highest in trained athletes and lowest in T2DM patients. Skeletal muscle Acetylcarnitine concentration showed a reciprocal distribution, with mean Acetylcarnitine concentration correlating with mean insulin sensitivity in each group. These results demonstrate that measuring Acetylcarnitine concentrations with 1 H-MRS is feasible on clinical MR scanners and support the hypothesis that T2DM patients are characterized by a decreased formation of Acetylcarnitine, possibly underlying decreased insulin sensitivity.
Joachim E. Wildberger - One of the best experts on this subject based on the ideXlab platform.
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Carnitine supplementation improves metabolic flexibility and skeletal muscle Acetylcarnitine formation in volunteers with impaired glucose tolerance: A randomised controlled trial.
EBioMedicine, 2019Co-Authors: Yvonne M. H. Bruls, Lucas Lindeboom, Esther Phielix, Matthijs K. C. Hesselink, Joachim E. Wildberger, Marlies De Ligt, Bas Havekes, Gert Schaart, Esther Kornips, Deborah M. MuoioAbstract:Abstract Background Type 2 diabetes patients and individuals at risk of developing diabetes are characterized by metabolic inflexibility and disturbed glucose homeostasis. Low carnitine availability may contribute to metabolic inflexibility and impaired glucose tolerance. Here, we investigated whether carnitine supplementation improves metabolic flexibility and insulin sensitivity in impaired glucose tolerant (IGT) volunteers. Methods Eleven IGT- volunteers followed a 36-day placebo- and L -carnitine treatment (2 g/day) in a randomised, placebo-controlled, double blind crossover design. A hyperinsulinemic-euglycemic clamp (40 mU/m2/min), combined with indirect calorimetry (ventilated hood) was performed to determine insulin sensitivity and metabolic flexibility. Furthermore, metabolic flexibility was assessed in response to a high-energy meal. Skeletal muscle Acetylcarnitine concentrations were measured in vivo using long echo time proton magnetic resonance spectroscopy (1H-MRS, TE=500 ms) in the resting state (7:00AM and 5:00PM) and after a 30-min cycling exercise. Twelve normal glucose tolerant (NGT) volunteers were included without any intervention as control group. Results Metabolic flexibility of IGT-subjects completely restored towards NGT control values upon carnitine supplementation, measured during a hyperinsulinemic-euglycemic clamp and meal test. In muscle, carnitine supplementation enhanced the increase in resting Acetylcarnitine concentrations over the day (delta 7:00 AM versus 5:00 PM) in IGT-subjects. Furthermore, carnitine supplementation increased post-exercise Acetylcarnitine concentrations and reduced long-chain acylcarnitine species in IGT-subjects, suggesting the stimulation of a more complete fat oxidation in muscle. Whole-body insulin sensitivity was not affected. Conclusion Carnitine supplementation improves Acetylcarnitine formation and rescues metabolic flexibility in IGT-subjects. Future research should investigate the potential of carnitine in prevention/treatment of type 2 diabetes.
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Longitudinal relaxation time editing for Acetylcarnitine detection with 1 H-MRS.
Magnetic resonance in medicine, 2016Co-Authors: Lucas Lindeboom, Matthijs K. C. Hesselink, Joachim E. Wildberger, Yvonne M. H. Bruls, Petronella A. Van Ewijk, Patrick Schrauwen, Vera B. Schrauwen-hinderlingAbstract:PURPOSE Acetylcarnitine formation is suggested to be crucial in sustaining metabolic flexibility and glucose homeostasis. Recently, we introduced a method to detect Acetylcarnitine in vivo with long TE 1 H-MRS. Differences in T1 relaxation time between lipids and Acetylcarnitine can be exploited for additional lipid suppression in subjects with high myocellular lipid levels. METHODS Acquisition of spectra with an inversion recovery sequence was alternated with standard signal acquisition to suppress short T1 metabolite signals. A proof of principle experiment was conducted in a lean subject and the new approach was subsequently tested in four overweight/obese subjects. RESULTS Using the new T1 editing approach, lipid signals in spectra of skeletal muscle can be (additionally) suppressed by a factor of 10 using a TI of 900 ms. Combination of the long TE protocol with the T1 editing resulted in a well-resolved Acetylcarnitine peak in the obese subjects. CONCLUSION The T1 editing approach suppresses short T1 metabolites and offers a new contrast in 1 H-MRS. The approach should be used in combination with a long TE in subjects with high lipid contamination for accurate quantification of the Acetylcarnitine concentration. Magn Reson Med 77:505-510, 2017. © 2016 International Society for Magnetic Resonance in Medicine.
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long echo time mr spectroscopy for skeletal muscle Acetylcarnitine detection
Journal of Clinical Investigation, 2014Co-Authors: Lucas Lindeboom, Christine I. H. C. Nabuurs, Joris Hoeks, Bram Brouwers, Esther Phielix, Matthijs K. C. Hesselink, Joachim E. Wildberger, Robert Stevens, Eline M Kooi, Timothy R. KovesAbstract:1 H-MRS) to measure skeletal muscle Acetylcarnitine concentrations on a clinical 3T scanner. We applied long-TE 1 H-MRS to measure Acetylcarnitine in endurance- trained athletes, lean and obese sedentary subjects, and type 2 diabetes mellitus (T2DM) patients to cover a wide spectrum in insulin sensitivity. A long-TE 1 H-MRS protocol was implemented for successful detection of skeletal muscle Acetylcarnitine in these individuals. There were pronounced differences in insulin sensitivity, as measured by hyperinsulinemic-euglycemic clamp, and skeletal muscle mitochondrial function, as measured by phosphorus-MRS ( 31 P-MRS), across groups. Insulin sensitivity and mitochondrial function were highest in trained athletes and lowest in T2DM patients. Skeletal muscle Acetylcarnitine concentration showed a reciprocal distribution, with mean Acetylcarnitine concentration correlating with mean insulin sensitivity in each group. These results demonstrate that measuring Acetylcarnitine concentrations with 1 H-MRS is feasible on clinical MR scanners and support the hypothesis that T2DM patients are characterized by a decreased formation of Acetylcarnitine, possibly underlying decreased insulin sensitivity.
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Long–echo time MR spectroscopy for skeletal muscle Acetylcarnitine detection
The Journal of clinical investigation, 2014Co-Authors: Lucas Lindeboom, Christine I. H. C. Nabuurs, Joris Hoeks, Bram Brouwers, Esther Phielix, M. Eline Kooi, Matthijs K. C. Hesselink, Joachim E. Wildberger, Robert Stevens, Timothy R. KovesAbstract:1 H-MRS) to measure skeletal muscle Acetylcarnitine concentrations on a clinical 3T scanner. We applied long-TE 1 H-MRS to measure Acetylcarnitine in endurance- trained athletes, lean and obese sedentary subjects, and type 2 diabetes mellitus (T2DM) patients to cover a wide spectrum in insulin sensitivity. A long-TE 1 H-MRS protocol was implemented for successful detection of skeletal muscle Acetylcarnitine in these individuals. There were pronounced differences in insulin sensitivity, as measured by hyperinsulinemic-euglycemic clamp, and skeletal muscle mitochondrial function, as measured by phosphorus-MRS ( 31 P-MRS), across groups. Insulin sensitivity and mitochondrial function were highest in trained athletes and lowest in T2DM patients. Skeletal muscle Acetylcarnitine concentration showed a reciprocal distribution, with mean Acetylcarnitine concentration correlating with mean insulin sensitivity in each group. These results demonstrate that measuring Acetylcarnitine concentrations with 1 H-MRS is feasible on clinical MR scanners and support the hypothesis that T2DM patients are characterized by a decreased formation of Acetylcarnitine, possibly underlying decreased insulin sensitivity.
