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Basic Research
Carnitine Orotate Complex Ameliorates Insulin Resistance and Hepatic Steatosis Through Carnitine Acetyltransferase Pathway
Jung-Hee Hong, Moon-Kyu Lee
Diabetes Metab J. 2021;45(6):933-947.   Published online August 19, 2021
DOI: https://doi.org/10.4093/dmj.2020.0223
  • 5,922 View
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  • 3 Web of Science
  • 3 Crossref
Graphical AbstractGraphical Abstract AbstractAbstract PDFPubReader   ePub   
Background
Carnitine orotate complex (Godex) has been shown to decrease glycated hemoglobin levels and improve steatosis in patients with type 2 diabetes mellitus with non-alcoholic fatty liver disease. However, the mechanisms of Godex in glucose metabolism remain unclear.
Methods
Male C57BL/6J mice were divided into four groups: normal-fat diet, high-fat diet, a high-fat diet supplemented with intraperitoneal injection of (500 mg or 2,000 mg/kg/day) Godex for 8 weeks. Computed tomography, indirect calorimetry, and histological analyses including electron microscopy of the liver were performed, and biochemical profiles and oral glucose tolerance test and insulin tolerance test were undertaken. Expressions of genes in the lipid and glucose metabolism, activities of oxidative phosphorylation enzymes, carnitine acetyltransferase, pyruvate dehydrogenase, and acetyl-coenzyme A (CoA)/CoA ratio were evaluated.
Results
Godex improved insulin sensitivity and significantly decreased fasting plasma glucose, homeostatic model assessment for insulin resistance, steatosis, and gluconeogenesis, with a marked increase in fatty acid oxidation as well as better use of glucose in high-fat diet-fed mice. It preserved mitochondrial function and ultrastructure, restored oxidative phosphorylation enzyme activities, decreased acetyl-CoA/CoA ratio, and increased carnitine acetyltransferase content and pyruvate dehydrogenase activity. Carnitine acetyltransferase knockdown partially reversed the effects of Godex in liver and in vitro.
Conclusion
Godex improved insulin resistance and steatosis by regulating carnitine acetyltransferase in liver in high-fat diet-fed mice.

Citations

Citations to this article as recorded by  
  • Impact of l-Carnitine Supplementation on Liver Enzyme Normalization in Patients with Chronic Liver Disease: A Meta-Analysis of Randomized Trials
    Hyunwoo Oh, Chan Hyuk Park, Dae Won Jun
    Journal of Personalized Medicine.2022; 12(7): 1053.     CrossRef
  • Prolonged Use of Carnitine-Orotate Complex (Godex®) Is Associated with Improved Mortality: A Nationwide Cohort Study
    Kye-Yeung Park, Sangmo Hong, Kyung-Soo Kim, Kyungdo Han, Cheol-Young Park
    Journal of Personalized Medicine.2022; 12(12): 1970.     CrossRef
  • The Role of Carnitine Orotate Complex in Fatty Liver
    Hyon-Seung Yi
    Diabetes & Metabolism Journal.2021; 45(6): 866.     CrossRef
Metabolic Risk/Epidemiology
Plasma Targeted Metabolomics Analysis for Amino Acids and Acylcarnitines in Patients with Prediabetes, Type 2 Diabetes Mellitus, and Diabetic Vascular Complications
Xin Li, Yancheng Li, Yuanhao Liang, Ruixue Hu, Wenli Xu, Yufeng Liu
Diabetes Metab J. 2021;45(2):195-208.   Published online March 9, 2021
DOI: https://doi.org/10.4093/dmj.2019.0209
  • 6,386 View
  • 204 Download
  • 14 Web of Science
  • 13 Crossref
Graphical AbstractGraphical Abstract AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
We hypothesized that specific amino acids or acylcarnitines would have benefits for the differential diagnosis of diabetes. Thus, a targeted metabolomics for amino acids and acylcarnitines in patients with diabetes and its complications was carried out.
Methods
A cohort of 54 normal individuals and 156 patients with type 2 diabetes mellitus and/or diabetic complications enrolled from the First Affiliated Hospital of Jinzhou Medical University was studied. The subjects were divided into five main groups: normal individuals, impaired fasting glucose, overt diabetes, diabetic microvascular complications, and diabetic peripheral vascular disease. The technique of tandem mass spectrometry was applied to obtain the plasma metabolite profiles. Metabolomics multivariate statistics were applied for the metabolic data analysis and the differential metabolites determination.
Results
A total of 10 cross-comparisons within diabetes and its complications were designed to explore the differential metabolites. The results demonstrated that eight comparisons existed and yielded significant metabolic differences. A total number of 24 differential metabolites were determined from six selected comparisons, including up-regulated amino acids, down-regulated medium-chain and long-chain acylcarnitines. Altered differential metabolites provided six panels of biomarkers, which were helpful in distinguishing diabetic patients.
Conclusion
Our results demonstrated that the biomarker panels consisted of specific amino acids and acylcarnitines which could reflect the metabolic variations among the different stages of diabetes and might be useful for the differential diagnosis of prediabetes, overt diabetes and diabetic complications.

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Review
Regulation of Muscle Pyruvate Dehydrogenase Complex in Insulin Resistance: Effects of Exercise and Dichloroacetate
Dumitru Constantin-Teodosiu
Diabetes Metab J. 2013;37(5):301-314.   Published online October 17, 2013
DOI: https://doi.org/10.4093/dmj.2013.37.5.301
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  • 80 Download
  • 47 Crossref
AbstractAbstract PDFPubReader   

Since the mitochondrial pyruvate dehydrogenase complex (PDC) controls the rate of carbohydrate oxidation, impairment of PDC activity mediated by high-fat intake has been advocated as a causative factor for the skeletal muscle insulin resistance, metabolic syndrome, and the onset of type 2 diabetes (T2D). There are also situations where muscle insulin resistance can occur independently from high-fat dietary intake such as sepsis, inflammation, or drug administration though they all may share the same underlying mechanism, i.e., via activation of forkhead box family of transcription factors, and to a lower extent via peroxisome proliferator-activated receptors. The main feature of T2D is a chronic elevation in blood glucose levels. Chronic systemic hyperglycaemia is toxic and can lead to cellular dysfunction that may become irreversible over time due to deterioration of the pericyte cell's ability to provide vascular stability and control to endothelial proliferation. Therefore, it may not be surprising that T2D's complications are mainly macrovascular and microvascular related, i.e., neuropathy, retinopathy, nephropathy, coronary artery, and peripheral vascular diseases. However, life style intervention such as exercise, which is the most potent physiological activator of muscle PDC, along with pharmacological intervention such as administration of dichloroacetate or L-carnitine can prove to be viable strategies for treating muscle insulin resistance in obesity and T2D as they can potentially restore whole body glucose disposal.

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