Abnormal metabolic processes involved in the pathogenesis of non‑alcoholic fatty liver disease (Review)

Shao, Mingmei; Ye, Zixiang; Qin, Yanhong; Wu, Tao

doi:10.3892/etm.2020.9154

Cited by 40 publications

(31 citation statements)

References 145 publications

(160 reference statements)

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“…Supplementation with carnitine may have a positive effect on the β-oxidation of fatty acids in mitochondria, thereby promoting lipid metabolism by boosting the uptake of fatty acids and eventually reducing fat accumulation in hepatocytes. It is known that NAFLD is associated with an imbalance in a variety of metabolic networks, among which abnormal lipid metabolism is the core pathological metabolic process ( 49 ). The immediate cause of NAFLD is high levels of triglycerides (TG) and serum free fatty acids (FFAs).…”

Section: Role Of Carnitine In the Pathogenesis Of Nafld And Associated Diseasesmentioning

confidence: 99%

“…An important mechanism by which carnitine improves IR is enhancing the oxidation of mitochondrial long-chain acyl-CoAs ( Figure 2 ) ( 55 ). Accumulation of long-chain acyl-CoAs and other FA metabolites impairs insulin signaling and leads to the development of IR, a crucial pathophysiological factor for carbohydrate metabolism disorders consistent with the development of NAFLD ( 49 ). Since abnormal mitochondrial function is associated with IR ( 56 ), carnitine therapy can also reduce IR by improving mitochondrial function ( 56 ).…”

Section: Role Of Carnitine In the Pathogenesis Of Nafld And Associated Diseasesmentioning

confidence: 99%

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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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Section: Role Of Carnitine In the Pathogenesis Of Nafld And Associated Diseasesmentioning

confidence: 99%

Section: Role Of Carnitine In the Pathogenesis Of Nafld And Associated Diseasesmentioning

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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“…The reduction in hepcidin expression may also cause ineffective erythropoiesis, leading to iron-loading anaemia deficiency as previously reported elsewhere [ 18 ]. The dysregulation of hepcidin levels is also associated with non-alcoholic fatty liver disease (NAFLD), a metabolic disorder that is closely associated with hyperglycaemia and insulin resistance [ 19 , 20 ]. The elevated levels of hepcidin in NALFD leads to the excessive accumulation of hepatic iron stores coupled with a deficiency in serum levels [ 21 ].…”

Section: Introductionmentioning

confidence: 99%

Body weight and its influence on hepcidin levels in patients with type 2 diabetes: A systematic review and meta-analysis of clinical studies

Ndevahoma

Mukesi

Dludla

et al. 2021

Heliyon

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Introduction: Iron profiles in patients with type 2 diabetes (T2D) are inconsistent. In this study, we assessed the levels of hepcidin, a regulatory protein involved in iron homoeostasis, in patients with T2D. We further evaluated the surrogate markers of hepcidin action, particularly those associated with erythropoiesis. Methods: This systematic review and meta-analysis was reported following the Meta-analysis Of Observational Studies in Epidemiology (MOOSE) guidelines. We searched for relevant studies in electronic databases from inception until 31 October 2020 without any language restriction. The random effects model was used to calculate effect estimates, and outcomes were reported as either standardised mean difference (SMD) or mean differences (MD), 95 percent confidence interval (95% CI). Results: Eleven studies involving 2 620 participants were included in this study. Patients with T2D had a slight increase in hepcidin levels when compared to controls SMD: 0.07 [95% CI:-0.30, 0.44]. The subgroup analysis showed that studies involving patients with T2D who were overweight reported elevated hepcidin levels SMD: 0.35 [95% CI: 0.07, 0.62] whilst those with grade I obesity described reduced levels SMD:-0.42 [95% CI:-1.21, 0.38]. All T2D patients had low levels of haemoglobin MD:-0.23 g/dl [95% CI:-0.46,-0.01] irrespective of body weight. Conclusion: The levels of hepcidin are altered in patients with T2D and are disproportionately influenced by weight. Moreover, patients with T2D present with subclinical anaemia despite elevated iron stores. The regulation of hepcidin in patients with T2D is dependent on several factors and vary greatly, thus its sole use in clinical settings may be less beneficial.

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“…Nonalcoholic fatty liver disease (NAFLD) is one of the most commonly occurring chronic liver disorders [ 1 ]. It is caused by inadequate lipid metabolism without alcohol consumption [ 2 ]. In general, lipid metabolism is regulated through various pathways such as uptake of circulating lipids, de novo lipogenesis, fatty acid oxidation (lipolysis), and secretion [ 2 ].…”

Section: Introductionmentioning

confidence: 99%

“…It is caused by inadequate lipid metabolism without alcohol consumption [ 2 ]. In general, lipid metabolism is regulated through various pathways such as uptake of circulating lipids, de novo lipogenesis, fatty acid oxidation (lipolysis), and secretion [ 2 ]. However, dysregulated lipid metabolism results in excessive lipid accumulation in the form of triglycerides (TG) in the liver, that plays a major role in the development of NAFLD [ 2 ].…”

Section: Introductionmentioning

confidence: 99%

Methyl Brevifolincarboxylate Attenuates Free Fatty Acid-Induced Lipid Metabolism and Inflammation in Hepatocytes through AMPK/NF-κB Signaling Pathway

Geethangili

Lin

Mersmann

et al. 2021

IJMS

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The prevalence of non-alcoholic fatty liver disease (NAFLD) is one of the leading causes of chronic liver diseases worldwide. This study examined the potential protective effects of a naturally occurring polyphenolic compound, methyl brevifolincarboxylate (MBC) on fatty liver injury in vitro. The results showed that MBC at its non-cytotoxic concentrations, reduced lipid droplet accumulation and triglyceride (TG) levels in the oleic acid (OA)-treated human hepatocarcinoma cell line, SK-HEP-1 and murine primary hepatocytes. In OA-treated SK-HEP-1 cells and primary murine hepatocytes, MBC attenuated the mRNA expression levels of the de novo lipogenesis molecules, acetyl-coenzyme A carboxylase (Acc1), fatty acid synthase (Fasn) and sterol regulatory element binding protein 1c (Srebp1c). MBC promoted the lipid oxidation factor peroxisome proliferator activated receptor-α (Pparα), and its target genes, carnitine palmitoyl transferase 1 (Cpt1) and acyl-coenzyme A oxidase 1 (Acox1) in both the SK-HEP-1 cells and primary murine hepatocytes. The mRNA results were further supported by the attenuated protein expression of lipogenesis and lipid oxidation molecules in OA-treated SK-HEP-1 cells. The MBC increased the expression of AMP activated protein kinase (AMPK) phosphorylation. On the other hand, MBC treatment dampened the inflammatory mediator’s, tumor necrosis factor (TNF)-α, interleukin-6 (IL-6), IL-8, and IL-1β secretion, and nuclear factor (NF)-κB expression (mRNA and protein) through reduced reactive oxygen species production in OA-treated SK-HEP-1 cells. Taken together, our results demonstrated that MBC possessed potential protective effects against NAFLD in vitro by amelioration of lipid metabolism and inflammatory markers through the AMPK/NF-κB signaling pathway.

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Abnormal metabolic processes involved in the pathogenesis of non‑alcoholic fatty liver disease (Review)

Cited by 40 publications

References 145 publications

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

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

Body weight and its influence on hepcidin levels in patients with type 2 diabetes: A systematic review and meta-analysis of clinical studies

Methyl Brevifolincarboxylate Attenuates Free Fatty Acid-Induced Lipid Metabolism and Inflammation in Hepatocytes through AMPK/NF-κB Signaling Pathway

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