Carnitine: a nutritional, biosynthetic, and functional perspective

Steiber, Alison; Kerner, János; Hoppel, Charles L.

doi:10.1016/j.mam.2004.06.006

Cited by 345 publications

(235 citation statements)

References 96 publications

(104 reference statements)

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“…In omnivorous humans, animal products provide an estimated 75% of whole body carnitine reserves (23). Conversely, vegetarians meet most of their carnitine needs via endogenous production (23).…”

Section: Discussionmentioning

confidence: 99%

Carnitine Insufficiency Caused by Aging and Overnutrition Compromises Mitochondrial Performance and Metabolic Control

Noland¹,

Koves²,

Seiler³

et al. 2009

Journal of Biological Chemistry

282

338

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In addition to its essential role in permitting mitochondrial import and oxidation of long chain fatty acids, carnitine also functions as an acyl group acceptor that facilitates mitochondrial export of excess carbons in the form of acylcarnitines. Recent evidence suggests carnitine requirements increase under conditions of sustained metabolic stress. Accordingly, we hypothesized that carnitine insufficiency might contribute to mitochondrial dysfunction and obesity-related impairments in glucose tolerance. Consistent with this prediction whole body carnitine dimunition was identified as a common feature of insulin-resistant states such as advanced age, genetic diabetes, and diet-induced obesity. In rodents fed a lifelong (12 month) high fat diet, compromised carnitine status corresponded with increased skeletal muscle accumulation of acylcarnitine esters and diminished hepatic expression of carnitine biosynthetic genes. Diminished carnitine reserves in muscle of obese rats was accompanied by marked perturbations in mitochondrial fuel metabolism, including low rates of complete fatty acid oxidation, elevated incomplete ␤-oxidation, and impaired substrate switching from fatty acid to pyruvate. These mitochondrial abnormalities were reversed by 8 weeks of oral carnitine supplementation, in concert with increased tissue efflux and urinary excretion of acetylcarnitine and improvement of whole body glucose tolerance. Acetylcarnitine is produced by the mitochondrial matrix enzyme, carnitine acetyltransferase (CrAT). A role for this enzyme in combating glucose intolerance was further supported by the finding that CrAT overexpression in primary human skeletal myocytes increased glucose uptake and attenuated lipid-induced suppression of glucose oxidation. These results implicate carnitine insufficiency and reduced CrAT activity as reversible components of the metabolic syndrome.Disturbances in mitochondrial genesis, morphology, and function are increasingly recognized as components of insulin resistance and the metabolic syndrome (1-3). Still unclear is whether poor mitochondrial performance is a predisposing factor or a consequence of the disease process. The latter view is supported by recent animal studies linking diet-induced insulin resistance to a dysregulated mitochondrial phenotype in skeletal muscle, marked by excessive ␤-oxidation, impaired substrate switching during the fasted to fed transition, and coincident reduction of organic acid intermediates of the tricarboxylic acid cycle (4, 5). In these studies, both diet-induced and genetic forms of insulin resistance were specifically linked to high rates of incomplete fat oxidation and intramuscular accumulation of fatty acylcarnitines, byproducts of lipid catabolism that are produced under conditions of metabolic stress (5, 6). Most compelling, we showed that genetically engineered inhibition of fat oxidation lowered intramuscular acylcarnitine levels and preserved glucose tolerance in mice fed a high fat diet (5, 7). In aggregate, the findings established a stron...

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Section: Discussionmentioning

confidence: 99%

Carnitine Insufficiency Caused by Aging and Overnutrition Compromises Mitochondrial Performance and Metabolic Control

Noland¹,

Koves²,

Seiler³

et al. 2009

Journal of Biological Chemistry

282

338

View full text Add to dashboard Cite

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“…Na medida em que é fundamental para a produção de ATP, a L-carnitina é tema recorrente na área de exercício físico. 107,108 Constituintes químicos principais, responsáveis pela atividade antioxidante Em muitos dos trabalhos relatados, identificou-se o princípio antioxidante principal, como no caso do azeite de oliva, o hidroxitirosol, 109 ou apenas isolaram-se frações detentoras de atividade antioxidante. Deve-se ressaltar que a atribuição inequívoca de atividade antioxidante biológica, mesmo que in vitro ou ex vivo, a compostos isolados e identificados de um extrato não é tarefa fácil, pois vários fatores têm de ser avaliados.…”

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Fontes vegetais naturais de antioxidantes

et al. 2009

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“…This hypothesis postulates that emerging FAO dysregulating prior to insulin resistance and glucose deterioration may provide a unique window to discover novel biomarkers for early detection of diabetes. Carnitine is known to play a pivotal role in transporting longchain fatty acids across the mitochondrial inner membrane for b-oxidation (5). As intermediates of carnitine metabolism, acylcarnitines were previously used to screen for genetic defects in FAO (6).…”

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confidence: 99%

Early Prediction of Developing Type 2 Diabetes by Plasma Acylcarnitines: A Population-Based Study

et al. 2016

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OBJECTIVEAcylcarnitines were suggested as early biomarkers even prior to insulin resistance in animal studies, but their roles in predicting type 2 diabetes were unknown. Therefore, we aimed to determine whether acylcarnitines could independently predict type 2 diabetes by using a targeted metabolic profiling approach. RESEARCH DESIGN AND METHODSA population-based prospective study was conducted among 2,103 communityliving Chinese individuals aged 50-70 years from Beijing and Shanghai with a mean follow-up duration of 6 years. Fasting glucose, glycohemoglobin, and insulin were determined at baseline and in a follow-up survey. Baseline plasma acylcarnitines were profiled by liquid chromatography-tandem mass spectrometry. RESULTSOver the 6-year period, 507 participants developed diabetes. A panel of acylcanitines, especially with long chain, was significantly associated with increased risk of type 2 diabetes. The relative risks of type 2 diabetes per SD increase of the predictive model score were 2.48 (95% CI 2.20-2.78) for the conventional and 9.41 (95% CI 7.62-11.62) for the full model including acylcarnitines, respectively. Moreover, adding selected acylcarnitines substantially improved predictive ability for incident diabetes, as area under the receiver operator characteristic curve improved to 0.89 in the full model compared with 0.73 in the conventional model. Similar associations were obtained when the predictive models were established separately among Beijing or Shanghai residents. CONCLUSIONSA panel of acylcarnitines, mainly involving mitochondrial lipid dysregulation, significantly improved predictive ability for type 2 diabetes beyond conventional risk factors. These findings need to be replicated in other populations, and the underlying mechanisms should be elucidated.The escalating global epidemic of type 2 diabetes has contributed considerably to socioeconomic burdens in both developed and developing countries (1). To understand biological mechanisms and improve clinical predictions, it is essential to identify novel biomarkers to enhance the capability to predict early pathophysiological changes (2). As a largely preventable disease, early prediction is the key to control the epidemic trend of type 2 diabetes, particularly in those countries with

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Carnitine: a nutritional, biosynthetic, and functional perspective

Cited by 345 publications

References 96 publications

Carnitine Insufficiency Caused by Aging and Overnutrition Compromises Mitochondrial Performance and Metabolic Control

Carnitine Insufficiency Caused by Aging and Overnutrition Compromises Mitochondrial Performance and Metabolic Control

Fontes vegetais naturais de antioxidantes

Early Prediction of Developing Type 2 Diabetes by Plasma Acylcarnitines: A Population-Based Study

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