Mediterranean Diet: The Beneficial Effects of Lycopene in Non-Alcoholic Fatty Liver Disease

Abenavoli, Ludovico; Procopio, Anna; Paravati, Maria Rosaria; Costa, Giosuè; Milić, Nataša; Alcaro, Stefano; Luzza, Francesco

doi:10.3390/jcm11123477

Cited by 21 publications

(17 citation statements)

References 86 publications

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“…In this study, the transcriptome combined with KEGG analysis further identified a significant regulatory role for lycopene in pathways associated with lipid metabolism, inflammation, fibrosis, and apoptosis. Particularly, there was pronounced enrichment in inflammation-related pathways, aligning with prior research demonstrating lycopene’s inflammation-reducing effects in organism induced by a HFD through ROS regulation . KEGG pathway analysis additionally revealed significant regulation of advanced glycation end products and TH17 cell differentiation, indicating the insulin resistance and immunomodulatory effects of lycopene.…”

Section: Discussionmentioning

confidence: 99%

“…Currently, several phytochemicals exhibiting potential anti-inflammatory properties, such as curcumin, diosmetin, quercetin, and astaxanthin (a type of carotenoid), have emerged as promising candidates for NASH treatment. − It is worth noting that some of these compounds have been reported to regulate the phosphorylation of ASK. , Lycopene, as a highly potent antioxidant carotenoid, possesses diverse pharmacological characteristics, including anti-inflammatory, antioxidant, and photoprotective effects. − Its efficacy in controlling lipid metabolism has rendered it advantageous in the treatment of NAFLD. ,, Previous research has proven that a high intake of lycopene (12 mg/kg/day) can alleviate atherogenic high-fat-induced liver inflammation in a mouse model, including restoring dyslipidemia and hepatic dysfunction . The beneficial effects of lycopene are often attributed to its antioxidant stress; however, its underlying mechanisms for improving ER stress in the progression of NASH remain unclear.…”

Section: Introductionmentioning

confidence: 99%

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Lycopene Alleviates Endoplasmic Reticulum Stress in Steatohepatitis through Inhibition of the ASK1–JNK Signaling Pathway

Song,

Sun,

Liu

et al. 2024

J. Agric. Food Chem.

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Lycopene has been proven to alleviate nonalcoholic steatohepatitis (NASH), but the precise mechanisms are inadequately elucidated. In this study, we found a previously unknown regulatory effect of lycopene on the apoptosis signalregulating kinase 1 (ASK1) signaling pathway in both in vivo and in vitro models. Lycopene supplementation (3 and 6 mg/kg/day) exhibited a significant reduction in lipid accumulation, inflammation, and fibrosis of the liver in mice fed with a high-fat/highcholesterol diet or a methionine-choline-deficient diet. RNA sequencing uncovered that the mitogen-activated protein kinases signaling pathway, which is closely associated with inflammation and endoplasmic reticulum (ER) stress, was significantly downregulated by lycopene. Furthermore, we found lycopene ameliorated ER swelling and decreased the expression levels of ER stress markers (i.e., immunoglobulin heavy chain binding protein, C/EBP homologous protein, and X-box binding protein 1s). Especially, the inositol-requiring enzyme 1α involved in the ASK1 phosphorylation was inhibited by lycopene, resulting in the decline of the subsequent c-Jun N-terminal kinase (JNK) signaling cascade. ASK1 inhibitor DQOP-1 eliminated the lycopeneinduced inhibition of the ASK1−JNK pathway in oleic acid and palmitic acid-induced HepG2 cells. Molecular docking further indicated hydrophobic interactions between lycopene and ASK1. Collectively, our research indicates that lycopene can alleviate ER stress and attenuate inflammation cascades and lipid accumulation by inhibiting the ASK1−JNK pathway.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Lycopene Alleviates Endoplasmic Reticulum Stress in Steatohepatitis through Inhibition of the ASK1–JNK Signaling Pathway

Song,

Sun,

Liu

et al. 2024

J. Agric. Food Chem.

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“…Studies have reported that lycopene can activate the essential signaling pathway in redox homeostasis (nuclear factor erythroid 2-related factor 2 pathway) to promote the expression of antioxidant genes, reduce oxidative stress, and repair liver damage [ 9 , 10 ]. Additionally, several preclinical and clinical studies have been conducted to validate the protective and preventive effects of lycopene on NAFLD [ 11 ].…”

Section: Introductionmentioning

confidence: 99%

Identification and Evaluation of Hub Long Noncoding RNAs and mRNAs in High Fat Diet Induced Liver Steatosis

Sui

Pan

et al. 2023

Nutrients

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Nonalcoholic fatty liver disease (NAFLD) is considered the most prevalent chronic liver disease, but the understanding of the mechanism of NAFLD is still limited. The aim of our study was to explore hub lncRNAs and mRNAs and pathological processes in high-fat diet (HFD)-induced and lycopene-intervened liver steatosis. We analyzed the gene profiles in the GSE146627 dataset from the Gene Expression Omnibus (GEO) database to identify differentially expressed lncRNAs and mRNAs, and we constructed coexpression networks based on weighted gene coexpression network analysis (WGCNA). The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases were utilized for functional enrichment analysis. We found that the turquoise, blue, brown, yellow, green, and black modules were significantly correlated with NAFLD. Functional enrichment analysis revealed that some hub lncRNAs (Smarca2, Tacc1, Flywch1, and Mef2c) might be involved in the regulation of the inflammatory and metabolic pathways (such as TNF signaling, metabolic, mTOR signaling, MAPK signaling, and p53 signaling pathways) in NAFLD. The establishment of an NAFLD mouse model confirmed that lycopene supply attenuated hepatic steatosis in HFD-induced NAFLD. Our analysis revealed that the inflammatory and metabolic pathways may be crucially involved in the pathogenesis of NAFLD, and hub lncRNAs provide novel biomarkers, therapeutic ideas, and targets for NAFLD. Moreover, lycopene has the potential to be a phytochemical for the prevention of HFD-induced liver steatosis.

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“…( 19 ). Some animal studies have reported LY supplementation ameliorated hepatic steatosis and decreased serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels in obese rodents ( 20 ), indicating the protective effect of LY on NAFLD. However, the potential mechanisms are largely unknown.…”

Section: Introductionmentioning

confidence: 99%

Lycopene prevents non-alcoholic fatty liver disease through regulating hepatic NF-κB/NLRP3 inflammasome pathway and intestinal microbiota in mice fed with high-fat and high-fructose diet

et al. 2023

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Lycopene (LY) belongs to carotenoids and is abundant in red fruits and vegetables. Several previous studies suggested that LY is beneficial for ameliorating non-alcoholic fatty liver disease (NAFLD), while the potential mechanisms are unclear. The present study aimed to clarify the potential mechanisms of LY in preventing NAFLD via exploring the hepatic NF-κB/NLRP3 inflammasome pathway and intestinal microbiota composition in high-fat and high-fructose diet (HFFD)-fed mice. Fifty eight-week-old male C57BL/6J mice were randomly assigned into 5 groups: Normal control group (NC); HFFD group; HFFD with low dose of lycopene group (LLY, 20 mg/kg/d); HFFD with high dose of lycopene group (HLY, 60 mg/kg/d) and HFFD with resveratrol group (RSV, 50 mg/kg/d, positive control). After 8 weeks, feces were collected and the 12 h fasted mice were sacrificed to acquire tissues and blood for parameters measurement. The results showed that the mice in LLY, HLY and RSV groups had significantly lower body weight gain, weight of white adipose tissue, serum levels of high density lipoprotein-cholesterol (HDL-C), low density lipoprotein-cholesterol (LDL-C), lipopolysaccharide (LPS), alanine aminotransferase (ALT), and hepatic concentrations of triglyceride (TG) and interleukin-6 (IL-6) than that in the HFFD group (p < 0.05). HLY and RSV groups also displayed lower serum levels of TG, total cholesterol (TC) and hepatic levels of tumor necrosis factor-α (TNF-α) than the HFFD group (p < 0.05). Liver protein expressions of NLRP3, Pro-Caspase-1, Caspase-1 and NF-κB were lower in the LLY, HLY and RSV groups than those in the HFFD group (p < 0.05). The feces of LY -treated mice had higher relative levels of SCFAs producing bacteria Allobaculum and lower destructive bacteria, including Firmicutes, Lachnospiraceae_NK4A136_group, Desulfovibrio, and Alistipes over the HFFD group (p < 0.05). RSV group also displayed lower fecal levels of Lachnospiraceae_NK4A136_group, Desulfovibrio, and Alistipes than the HFFD group (p < 0.05). In conclusion, LY might prevent NAFLD by suppressing hepatic NF-κB/NLRP3 inflammasome pathway and attenuating gut microbiota dysbiosis.

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Mediterranean Diet: The Beneficial Effects of Lycopene in Non-Alcoholic Fatty Liver Disease

Cited by 21 publications

References 86 publications

Lycopene Alleviates Endoplasmic Reticulum Stress in Steatohepatitis through Inhibition of the ASK1–JNK Signaling Pathway

Lycopene Alleviates Endoplasmic Reticulum Stress in Steatohepatitis through Inhibition of the ASK1–JNK Signaling Pathway

Identification and Evaluation of Hub Long Noncoding RNAs and mRNAs in High Fat Diet Induced Liver Steatosis

Lycopene prevents non-alcoholic fatty liver disease through regulating hepatic NF-κB/NLRP3 inflammasome pathway and intestinal microbiota in mice fed with high-fat and high-fructose diet

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