The Regulation of Energy Metabolism Pathways Through L-Carnitine Homeostasis

Liepinsh, Edgars; Kalvinsh, Ivars; Dambrova, Maija

doi:10.5772/22478

Cited by 11 publications

(12 citation statements)

References 81 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…L-carnitine is an important factor that regulates fatty acid (FA) and glucose metabolism to achieve balanced cellular energy metabolism1. L-carnitine can be synthesized naturally from lysine and methionine in microorganisms, plants and animals2.…”

mentioning

confidence: 99%

Systemic regulation of L-carnitine in nutritional metabolism in zebrafish, Danio rerio

Qin

et al. 2017

Sci Rep

View full text Add to dashboard Cite

Excess fat accumulation has been observed widely in farmed fish; therefore, efficient lipid-lowering factors have obtained high attention in the current fish nutrition studies. Dietary L-carnitine can increase fatty acid β-oxidation in mammals, but has produced contradictory results in different fish species. To date, the mechanisms of metabolic regulation of L-carnitine in fish have not been fully determined. The present study used zebrafish to investigate the systemic regulation of nutrient metabolism by dietary L-carnitine supplementation. L-carnitine significantly decreased the lipid content in liver and muscle, accompanied by increased concentrations of total and free carnitine in tissues. Meanwhile, L-carnitine enhanced mitochondrial β-oxidation activities and the expression of carnitine palmitoyltransferase 1 mRNA significantly, whereas it depressed the mRNA expression of adipogenesis-related genes. In addition, L-carnitine caused higher glycogen deposition in the fasting state, and increased and decreased the mRNA expressions of gluconeogenesis-related and glycolysis-related genes, respectively. L-carnitine also increased the hepatic expression of mTOR in the feeding state. Taken together, dietary L-carnitine supplementation decreased lipid deposition by increasing mitochondrial fatty acid β-oxidation, and is likely to promote protein synthesis. However, the L-carnitine-enhanced lipid catabolism would cause a decrease in glucose utilization. Therefore, L-carnitine has comprehensive effects on nutrient metabolism in fish.

show abstract

mentioning

confidence: 99%

Systemic regulation of L-carnitine in nutritional metabolism in zebrafish, Danio rerio

Qin

et al. 2017

Sci Rep

View full text Add to dashboard Cite

show abstract

“…According to our data, L‐carnitine has the capacity to significantly reduce choline‐deficient diet‐induced myocardial fibrosis and to maintain cardiac function . The fact that L‐carnitine has no significant effect on MMP‐9, MMP‐2, TIMP‐1, or TIMP‐2 activities in both choline‐deprived and control rats suggests that the beneficial effects of L‐carnitine are not mediated through modulation of tissue expression of MMPs and TIMPs, key enzymes in the regulation of interstitial tissue composition , but probably through alternative mechanisms , such as nitric oxide , oxidative stress , inflammation or PPAR activity modulation. It is unlikely that longer exposure to L‐carnitine might change the expression of MMPs and TIMPs substantially, since at this time, functional changes are already evident .…”

Section: Discussionmentioning

confidence: 74%

Immunohistochemical determination of the extracellular matrix modulation in a rat model of choline‐deprived myocardium: the effects of carnitine

Strilakou

Perelas

Lazaris

et al. 2015

Fundamemntal Clinical Pharma

View full text Add to dashboard Cite

Choline has been identified as an essential nutrient with crucial role in many vital biological functions. Recent studies have demonstrated that heart dysfunction can develop in the setting of choline deprivation even in the absence of underlying heart disease. Matrix metalloproteinases (MMPs) are responsible for extracellular matrix degradation, and the dysregulation of MMP-2 and MMP-9 has been involved in the pathogenesis of various cardiovascular disorders. The aim of the study was to investigate the role of MMPs and their inhibitors (TIMPs), in the pathogenesis of choline deficiency-induced cardiomyopathy, and the way they are affected by carnitine supplementation. Male Wistar Albino adult rats were divided into four groups and received standard or choline-deficient diet with or without L-carnitine in drinking water (0.15% w/v) for 1 month. Heart tissue immunohistochemistry for MMP-2, MMP-9, TIMP-1, and TIMP-2 was performed. Choline deficiency was associated with suppressed immunohistochemical expression of MMP-2 and an increased expression of TIMP-2 compared to control, while it had no impact on TIMP-1. MMP-9 expression was decreased without, however, reaching statistical significance. Carnitine did not affect MMP-2, MMP-9, TIMP-1 or TIMP-2 expression. The pattern of TIMP and MMP modulation observed in a choline deficiency setting appears to promote fibrosis. Carnitine, although shown to suppress fibrosis, does not seem to affect MMP-2, MMP-9, TIMP-1 or TIMP-2 expression. Further studies will be required to identify the mechanism underlying the beneficial effects of carnitine.

show abstract

“…L‐carnitine is a cofactor required by CPT I‐dependent LCFA transport, and a decreased cardiac content of L‐carnitine limits LCFA oxidation in heart mitochondria (Liepinsh et al ., ; Kuka et al ., ). Decreased availability of L‐carnitine can be achieved by the administration of 3‐(2,2,2‐trimethylhydrazinium)‐propionate (meldonium) (Liepinsh et al ., 2011a,b). As a result of decreased L‐carnitine content and inhibited CPT I‐dependent LCFA oxidation, an increase in glucose oxidation was observed.…”

Section: Introductionmentioning

confidence: 98%

Inhibition of L‐carnitine biosynthesis and transport by methyl‐γ‐butyrobetaine decreases fatty acid oxidation and protects against myocardial infarction

Liepinsh

Makrecka-Kūka

Kuka

et al. 2015

British J Pharmacology

View full text Add to dashboard Cite

BACKGROUND AND PURPOSEThe important pathological consequences of ischaemic heart disease arise from the detrimental effects of the accumulation of long-chain acylcarnitines in the case of acute ischaemia-reperfusion. The aim of this study is to test whether decreasing the L-carnitine content represents an effective strategy to decrease accumulation of long-chain acylcarnitines and to reduce fatty acid oxidation in order to protect the heart against acute ischaemia-reperfusion injury. KEY RESULTSIn this study, we used a novel compound, 4-[ethyl(dimethyl)ammonio]butanoate (Methyl-GBB), which inhibits γ-butyrobetaine dioxygenase (IC50 3 μM) and organic cation transporter 2 (OCTN2, IC50 3 μM), and, in turn, decreases levels of L-carnitine and acylcarnitines in heart tissue. Methyl-GBB reduced both mitochondrial and peroxisomal palmitate oxidation rates by 44 and 53% respectively. In isolated hearts treated with Methyl-GBB, uptake and oxidation rates of labelled palmitate were decreased by 40%, while glucose oxidation was increased twofold. Methyl-GBB (5 or 20 mg·kg ) attenuated the infarct size by 45% and improved 24 h survival of rats by 20-30%. CONCLUSIONS AND IMPLICATIONSReduction of L-carnitine and long-chain acylcarnitine content by the inhibition of OCTN2 represents an effective strategy to protect the heart against ischaemia-reperfusion-induced damage. Methyl-GBB treatment exerted cardioprotective effects and increased survival by limiting long-chain fatty acid oxidation and facilitating glucose metabolism. AbbreviationsAAR, area at risk; ACOX, acyl-CoA oxidase 1; ACSL, long-chain fatty acid CoA synthetase; AN, area of necrosis; BBOX, γ-butyrobetaine dioxygenase; CD36, fatty acid translocase; CPT I, carnitine palmitoyltransferase I; FABP, fatty acid binding protein; FAO, fatty acid oxidation; HR, heart rate; IHD, ischaemic heart disease; IS, infarct size; KH, Krebs-Henseleit; LAD, left anterior descending coronary artery; LCFA, long-chain fatty acids; LV, left ventricle; LVDP, left ventricle developed pressure; IntroductionIschaemic heart disease (IHD) is a major medical problem causing disability and death for millions of people annually (Lavie et al., 2009). The important pathological consequences of IHD arise from the detrimental effects of the accumulation of long-chain fatty acids (LCFAs) in the case of acute ischaemia-reperfusion (Wang and Lopaschuk, 2007;Liepinsh et al., 2013b). Therefore, pharmacological intervention that targets LCFA accumulation has been suggested for the development of novel treatment strategies to improve the clinical outcomes of patients with IHD (Horowitz et al., 2010;Lopaschuk et al., 2010). The main advantages of reduced LCFA oxidation are the reduction of energy waste through mitochondrial uncoupling induced by LCFA overload as well as the reduction of direct damage by LCFA metabolites on glucose metabolism and insulin signalling (Zhang et al., 2011). In addition, pharmacological manipulation of energy metabolism does not directly influence the haemodynamic parameters of th...

show abstract

The Regulation of Energy Metabolism Pathways Through L-Carnitine Homeostasis

Cited by 11 publications

References 81 publications

Systemic regulation of L-carnitine in nutritional metabolism in zebrafish, Danio rerio

Systemic regulation of L-carnitine in nutritional metabolism in zebrafish, Danio rerio

Immunohistochemical determination of the extracellular matrix modulation in a rat model of choline‐deprived myocardium: the effects of carnitine

Inhibition of L‐carnitine biosynthesis and transport by methyl‐γ‐butyrobetaine decreases fatty acid oxidation and protects against myocardial infarction

Contact Info

Product

Resources

About