The disruption of l-carnitine metabolism by aluminum toxicity and oxidative stress promotes dyslipidemia in human astrocytic and hepatic cells

Lemire, Joseph; Mailloux, Ryan J.; Darwich, Rami; Auger, Christopher; Appanna, Vasu D.

doi:10.1016/j.toxlet.2011.03.019

Cited by 41 publications

(38 citation statements)

References 47 publications

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“…L-carnitine is a metabolite that is critical for lipid metabolism, as it facilitates the transport of fatty acids into the mitochondrion, where β-oxidation occurs [56] . Hepatic damage causes a decrease in L-carnitine levels [57] , which was observed in the livers from rats in the OP group. The decrease in carnitine levels may prevent β-oxidation of lipids in the OP group, which in turn contributed to the observed energy insufficiency and liver damage.…”

Section: Energy Metabolismmentioning

confidence: 88%

Cordyceps sinensis protects against liver and heart injuries in a rat model of chronic kidney disease: a metabolomic analysis

et al. 2014

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Aim: To test the hypothesis that the traditional Chinese medicine Cordyceps sinensis could improve the metabolic function of extrarenal organs to achieve its anti-chronic kidney disease (CKD) effects. Methods: Male SD rats were divided into CKD rats (with 5/6-nephrectomy), CKD rats treated with Cordyceps sinensis (4 mg·kg -1 ·d -1 , po), and sham-operated rats. After an 8-week treatment, metabolites were extracted from the hearts and livers of the rats, and then subjected to 1 H-NMR-based metabolomic analysis. Results: Oxidative stress, energy metabolism, amino acid and protein metabolism and choline metabolism were considered as links between CKD and extrarenal organ dysfunction. Within the experimental period of 8 weeks, the metabolic disorders in the liver were more pronounced than in the heart, suggesting that CKD-related extrarenal organ dysfunctions occurred sequentially rather than simultaneously. Oral administration of Cordyceps sinensis exerted statistically significant rescue effects on the liver and heart by reversely regulating levels of those metabolites that are typically perturbed in CKD. Conclusion: Oral administration of Cordyceps sinensis significantly attenuates the liver and heart injuries in CKD rats. The 1 H NMRbased metabolomic approach has provided a systematic view for understanding of CKD and the drug treatment, which can also be used to elucidate the mechanisms of action of other traditional Chinese medicines.

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Section: Energy Metabolismmentioning

confidence: 88%

Cordyceps sinensis protects against liver and heart injuries in a rat model of chronic kidney disease: a metabolomic analysis

et al. 2014

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“…Like other ketoacids such as pyruvate and oxaloacetate, KG reacts with and nullifies ROS releasing succinate (KG's respective product) and CO 2 , by a process referred to as non-enzymatic decarboxylation. As KG is being syphoned towards ROS sequestration, Lcarnitine synthesis decreases due to a lack of this pivotal cofactor (Figure 11) (Lemire et al, 2011b). Fig.…”

Section: Anemia 416mentioning

confidence: 99%

“…The synthesis of L-carnitine is a multistep enzymatic process that requires the participation of lysine, methionine andketoglutarate (KG). The decrease in L-carnitine levels appear to be triggered by the diminished activity and expression of two key enzymes involved in its synthesis, namelybutyrobetainealdehyde dehydrogenase (BADH) and butyrobetaine dioxygenase (BBDOX) (Lemire et al, 2011b). Along with the downregulated enzymes, the impeded TCA cycle blocks the steady supply of KG needed for L-carnitine synthesis.…”

Section: Aluminum and Dyslipidemia: A Metabolic Perspectivementioning

confidence: 99%

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The Molecular Connection Between Aluminum Toxicity, Anemia, Inflammation and Obesity: Therapeutic Cues

Bignucolo¹,

Lemire²,

Auger³

et al. 2012

Anemia

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“…Indeed, ROS-exposed astrocytes are highly lipogenic and ineffective in performing β oxidation, a metabolic network dedicated to the catabolism of lipids (40). The channeling of αKG to quell oxidative stress is known to further arrest lipid degradation (41).…”

Section: Brain Metabolism and Alzheimer's Disease: The Prospect Of A mentioning

confidence: 99%

Brain metabolism and Alzheimer's disease: The prospect of a metabolite-based therapy

Thomas

Alhasawi

Auger

et al. 2015

The Journal of nutrition, health and aging

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The brain is one of the most energy-demanding organs in the body. It has evolved intricate metabolic networks to fulfill this need and utilizes a variety of substrates to generate ATP, the universal energy currency. Any disruption in the supply of energy results in various abnormalities including Alzheimer's disease (AD), a condition with markedly diminished cognitive ability. Astrocytes are an important participant in maintaining the cerebral ATP budget. However, under oxidative stress induced by numerous factors including aluminum toxicity, the ability of astroctyes to generate ATP is impaired due to dysfunctional mitochondria. This leads to globular, glycolytic, lipogenic and ATP-deficient astrocytes, cerebral characteristics common in AD patients. The reversal of these perturbations by such natural metabolites as pyruvate, α-ketoglutarate, acetoacetate and L-carnitine provides valuable therapeutic cues against AD.

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The disruption of l-carnitine metabolism by aluminum toxicity and oxidative stress promotes dyslipidemia in human astrocytic and hepatic cells

Cited by 41 publications

References 47 publications

Cordyceps sinensis protects against liver and heart injuries in a rat model of chronic kidney disease: a metabolomic analysis

Cordyceps sinensis protects against liver and heart injuries in a rat model of chronic kidney disease: a metabolomic analysis

The Molecular Connection Between Aluminum Toxicity, Anemia, Inflammation and Obesity: Therapeutic Cues

Brain metabolism and Alzheimer's disease: The prospect of a metabolite-based therapy

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