L-carnitine ameliorated fatty liver in high-calorie diet/STZ-induced type 2 diabetic mice by improving mitochondrial function

Xia, Yu; Li, Qing; Zhong, Weizhen; Dong, Jing; Zhu-lin, Wang; Wang, Chunbo

doi:10.1186/1758-5996-3-31

Cited by 45 publications

(48 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We added a mixture of 10 mM L-carnitine (Sigmatau Inc., Gaithersburg, MD) and 50 nM exendin-4 (Sigma Aldrich, St. Louis, MO) to the perfusate upon commencement of NELP. The chosen doses were based on previous reports (21)(22)(23)(24)(25) with effective protocols for reducing hepatocyte IRI and steatosis. Cholesterol, triglyceride (TG), and low-density lipoprotein (LDL) levels were then measured in the blood perfusate.…”

Section: Defatting Protocolmentioning

confidence: 99%

“…We selected L-carnitine (21) and exendin-4 (22)(23)(24) to increase the rate of fatty acid metabolism within the cytoplasm and mitochondria of hepatocytes. L-carnitine increases the rate of fatty acid transport to the mitochondria and, in fact, has been shown to be essential to b-oxidation of quarried fatty acids from the mitochondrial membrane.…”

Section: Reduction Of Iri and Steatosis With Nelpmentioning

confidence: 99%

See 1 more Smart Citation

Development of a normothermic extracorporeal liver perfusion system toward improving viability and function of human extended criteria donor livers

Banan¹,

Watson²,

Xu³

et al. 2016

Liver Transpl

View full text Add to dashboard Cite

Donor organ shortages have led to an increased interest in finding new approaches to recover organs from extended criteria donors (ECD). Normothermic extracorporeal liver perfusion (NELP) has been proposed as a superior preservation method to reduce ischemia/reperfusion injury (IRI), precondition suboptimal grafts, and treat ECD livers so that they can be successfully used for transplantation. The aim of this study was to investigate the beneficial effects of a modified NELP circuit on discarded human livers. Seven human livers that were rejected for transplantation were placed on a modified NELP circuit for 8 hours. Perfusate samples and needle core biopsies were obtained at hourly intervals. A defatting solution that contained exendin-4 (50 nM) and L-carnitine (10 mM) was added to the perfusate for 2 steatotic livers. NELP provided normal temperature, electrolytes, and pH and glucose levels in the perfusate along with physiological vascular flows and pressures. Functional, biochemical, and microscopic evaluation revealed no additional injuries to the grafts during NELP with an improved oxygen extraction ratio (>0.5) and stabilized markers of hepatic injury. All livers synthesized adequate amounts of bile and coagulation factors. We also demonstrated a mild reduction (10%) of macroglobular steatosis with the use of the defatting solution. Histology demonstrated normal parenchymal architecture and a minimal to complete lack of IRI at the end of NELP. In conclusion, a modified NELP circuit preserved hepatocyte architecture, recovered synthetic functions, and hepatobiliary parameters of ECD livers without additional injuries to the grafts. This approach has the potential to increase the donor pool for clinical transplantation. The major limiting factor of using extended criteria donor (ECD) grafts is their greater susceptibility to injury during cold preservation and lower tolerance for ischemia/reperfusion injury (IRI) upon reperfusion. Therefore, ECD grafts have been associated with a higher risk of posttransplant complications such as primary graft nonfunction and chronic cholangiopathy.(1-4) Machine perfusion has been investigated both as a preservation method to reduce IRI in ECD livers and as a method to assess the viability and function of suboptimal grafts prior to transplantation.(5-7)Currently, there are 3 variants of liver machine perfusion that are distinguished by the perfusate temperature: hypothermic, subnormothermic, and normothermic.

show abstract

Section: Defatting Protocolmentioning

confidence: 99%

Section: Reduction Of Iri and Steatosis With Nelpmentioning

confidence: 99%

Development of a normothermic extracorporeal liver perfusion system toward improving viability and function of human extended criteria donor livers

Banan¹,

Watson²,

Xu³

et al. 2016

Liver Transpl

View full text Add to dashboard Cite

show abstract

“…Recent studies have shown that L -carnitine plays an important role in reducing steatosis in patients with hepatitis C treated with IFN-α and ribavirin [33]. L -Carnitine supplements greatly improved glucose plasma levels, lipid profiles, and histological manifestations in patients with nonalcoholic steatohepatitis [34]. Therefore, β-HPC appears to retain the pharmacological effects of L -carnitine and treat disturbances in the hepatic lipid metabolism of obese rats.…”

Section: Discussionmentioning

confidence: 99%

Pharmacokinetic and Pharmacological Effects of β-Hydroxyphosphocarnitine in Animal Models

et al. 2014

View full text Add to dashboard Cite

The purpose of this research was to describe the pharmacokinetic parameters of β-hydroxyphosphocarnitine (β-HPC; CAS No. 1220955-20-3) after a single oral dose in rats and rabbits as well as to assess the impact of 14 weeks of β-HPC (100 mg/kg) treatment on the serum metabolites and liver enzymes, body weight, and hepatic steatosis of lean and obese Zucker fa/fa rats. In the case of the rat and rabbit study, the β-HPC area under the curve, biological half-life, and clearance were 2,174.4 versus 3,128 μg∙h/ml, 23.7 versus 8.87 h, and 13.9 versus 151.1 ml/h in the rats versus the rabbits, respectively. The values for the time of maximal concentration were 0.58 versus 1.53 h, for the maximal concentration, they were 62.4 versus 221.4 μg/ml, and for the absorption rate constant 0.02 versus 2.40 h^-1, respectively. In the case of the Zucker fa/fa rat study, β-HPC administered orally once a day reduced insulin, triglyceride, and cholesterol levels in the liver and serum; it also reduced weight gain and decreased liver steatosis in obese rats after 14 weeks. β-HPC could therefore potentially be used in the treatment of metabolic syndrome.

show abstract

“…L-carnitine supplementation reduces the chance of long-chain acylcarnitine accumulation in mitochondria space and therefore, protects membrane against destruction. Diabetes is along with oxidative stress which affects antioxidative defense against RoS [11,21]. Therefore, mitochondria protective effects of L-carnitine can be considered as Lcarnitine beneficial effects observed in STZ-induced diabetic rats.…”

Section: T a B L E 2 Body Weight Glucose Insulin And Adiponectin mentioning

confidence: 99%

“…Also, it has been reported that high dose of L-carnitine reduced diabetes severity and also improved cardiac function [10]. Xia Y. et al showed that oral administration of L-carnitine to mice was increased β-oxidation of fatty acids and also in liver maintained mitochondrial function [11].…”

mentioning

confidence: 99%

Effect of L-carnitine administration on serum insulin and adiponectin levels, and AMPK, APPL1 and PPAR? gene expression in STZ-induced diabetic rat liver

Shahouzehi¹,

Barkhordari²,

Aminizadeh³

et al. 2017

Ukr.Biochem.J.

View full text Add to dashboard Cite

show abstract

L-carnitine ameliorated fatty liver in high-calorie diet/STZ-induced type 2 diabetic mice by improving mitochondrial function

Cited by 45 publications

References 38 publications

Development of a normothermic extracorporeal liver perfusion system toward improving viability and function of human extended criteria donor livers

Development of a normothermic extracorporeal liver perfusion system toward improving viability and function of human extended criteria donor livers

Pharmacokinetic and Pharmacological Effects of β-Hydroxyphosphocarnitine in Animal Models

Effect of L-carnitine administration on serum insulin and adiponectin levels, and AMPK, APPL1 and PPAR? gene expression in STZ-induced diabetic rat liver

Contact Info

Product

Resources

About