The Importance of the Fatty Acid Transporter L-Carnitine in Non-Alcoholic Fatty Liver Disease (NAFLD)

Savić, Dragana; Hodson, Leanne; Neubauer, Stefan; Pavlides, Michael

doi:10.3390/nu12082178

Cited by 46 publications

(38 citation statements)

References 112 publications

(137 reference statements)

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“…Carnitine is involved in the transportation of long-chain fatty acids from the cytoplasm into mitochondria in which fatty acids can be catabolized via β-oxidation ( Longo et al., 2016 ). The low intake of essential amino acids, particularly methionine and lysine, results in decreased level of carnitine to cause NAFLD ( Krajcovicova-Kudlackova et al., 2000 ; Savic et al., 2020 ). Methionine can be converted to S-adenosylmethionine, a primary methyl donor transferring its methyl group to other molecules, such as phospholipids, nucleic acids, and proteins ( Noureddin et al., 2015 ).…”

Section: Discussionmentioning

confidence: 99%

A novel chicken model of fatty liver disease induced by high cholesterol and low choline diets

Lin¹,

Huang²,

Peng³

et al. 2021

Poultry Science

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Fatty liver diseases, common metabolic diseases in chickens, can lead to a decrease in egg production and sudden death of chickens. To solve problems caused by the diseases, reliable chicken models of fatty liver disease are required. To generate chicken models of fatty liver, 7-week-old ISA female chickens were fed with a control diet (17% protein, 5.3% fat, and 1,300 mg/kg choline), a low protein and high fat diet ( LPHF , 13% protein, 9.1% fat, and 1,300 mg/kg choline), a high cholesterol with low choline diet ( CLC , 17% protein, 7.6% fat with additional 2% cholesterol, and 800 mg/kg choline), a low protein, high fat, high cholesterol, and low choline diet ( LPHFCLC , 13% protein, 12.6% fat with additional 2% cholesterol, and 800 mg/kg choline) for 4 wk. Our data showed that the CLC and LPHFCLC diets induced hyperlipidemia. Histological examination and the content of hepatic lipids indicated that the CLC and LPHFCLC diets induced hepatic steatosis. Plasma dipeptidyl peptidase 4, a biomarker of fatty liver diseases in laying hens, increased in chickens fed with the CLC or LPHFCLC diets. Hepatic ballooning and immune infiltration were observed in these livers accompanied by elevated interleukin 1 beta and lipopolysaccharide induced tumor necrosis factor mRNAs suggesting that the CLC and LPHFCLC diets also caused steatohepatitis in these livers. These diets also induced hepatic steatosis in Plymouth Rock chickens. Thus, the CLC and LPHFCLC diets can be used to generate models for fatty liver diseases in different strains of chickens. In ISA chickens fed with the CLC diet, peroxisome proliferator-activated receptor γ, sterol regulatory element binding transcription factor 1, and fatty acid synthase mRNAs increased in the livers, suggesting that lipogenesis was enhanced by the CLC treatment. Our data show that treatment with CLC or LPHFCLC for 4 wk induces fatty liver disease in chickens. These diets can be utilized to rapidly generate chicken models for fatty liver research.

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Section: Discussionmentioning

confidence: 99%

A novel chicken model of fatty liver disease induced by high cholesterol and low choline diets

Lin¹,

Huang²,

Peng³

et al. 2021

Poultry Science

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show abstract

“…Fatty acid oxidation depends on internal mitochondrial transport, which is mediated by different mitochondrial membrane proteins (CPTs, CAT, and CACT) and by L-carnitine. Reduced levels of L-carnitine have been reported in NAFLD patients, which may contribute to reduced fatty acid oxidation and subsequent mitochondrial impairment and concomitant ROS production [54]. Supplementation with L-carnitine was shown to be associated with the improvement of liver inflammation and histological parameters in patients with NASH [55].…”

Section: Lipid Metabolism and Oxidative Stressmentioning

confidence: 99%

Role of Oxidative Stress in the Pathogenesis of Non-Alcoholic Fatty Liver Disease: Implications for Prevention and Therapy

et al. 2021

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Oxidative stress (OxS) is considered a major factor in the pathophysiology of inflammatory chronic liver diseases, including non-alcoholic liver disease (NAFLD). Chronic impairment of lipid metabolism is closely related to alterations of the oxidant/antioxidant balance, which affect metabolism-related organelles, leading to cellular lipotoxicity, lipid peroxidation, chronic endoplasmic reticulum (ER) stress, and mitochondrial dysfunction. Increased OxS also triggers hepatocytes stress pathways, leading to inflammation and fibrogenesis, contributing to the progression of non-alcoholic steatohepatitis (NASH). The antioxidant response, regulated by the Nrf2/ARE pathway, is a key component in this process and counteracts oxidative stress-induced damage, contributing to the restoration of normal lipid metabolism. Therefore, modulation of the antioxidant response emerges as an interesting target to prevent NAFLD development and progression. This review highlights the link between disturbed lipid metabolism and oxidative stress in the context of NAFLD. In addition, emerging potential therapies based on antioxidant effects and their likely molecular targets are discussed.

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“…When there is persistent excess or underutilization of certain fatty acids, non-metabolizable acyl-CoAs accumulate. In such situations, carnitine acts as a receiver for these acyl groups by removing them from the tissues and excreting them in the urine ( 20 ), or they get separated from carnitine and reused ( 34 ). Carnitine regulation of acetyl-CoA/CoA reduces the inhibition of many intramitochondrial enzymes involved in glucose and amino acid catabolism ( 35 ).…”

Section: Biological Characteristics Of Carnitinementioning

confidence: 99%

Role of Carnitine in Non-alcoholic Fatty Liver Disease and Other Related Diseases: An Update

Zhao

2021

Front. Med.

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Carnitine is an amino acid-derived substance that coordinates a wide range of biological processes. Such functions include transport of long-chain fatty acids from the cytoplasm to the mitochondrial matrix, regulation of acetyl-CoA/CoA, control of inter-organellar acyl traffic, and protection against oxidative stress. Recent studies have found that carnitine plays an important role in several diseases, including non-alcoholic fatty liver disease (NAFLD). However, its effect is still controversial, and its mechanism is not clear. Herein, this review provides current knowledge on the biological functions of carnitine, the “multiple hit” impact of carnitine on the NAFLD progression, and the downstream mechanisms. Based on the “multiple hit” hypothesis, carnitine inhibits β-oxidation, improves mitochondrial dysfunction, and reduces insulin resistance to ameliorate NAFLD. L-carnitine may have therapeutic role in liver diseases including non-alcoholic steatohepatitis, cirrhosis, hepatocellular carcinoma, alcoholic fatty liver disease, and viral hepatitis. We also discuss the prospects of L-carnitine supplementation as a therapeutic strategy in NAFLD and related diseases, and the factors limiting its widespread use.

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The Importance of the Fatty Acid Transporter L-Carnitine in Non-Alcoholic Fatty Liver Disease (NAFLD)

Cited by 46 publications

References 112 publications

A novel chicken model of fatty liver disease induced by high cholesterol and low choline diets

A novel chicken model of fatty liver disease induced by high cholesterol and low choline diets

Role of Oxidative Stress in the Pathogenesis of Non-Alcoholic Fatty Liver Disease: Implications for Prevention and Therapy

Role of Carnitine in Non-alcoholic Fatty Liver Disease and Other Related Diseases: An Update

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