Molecular Mechanisms: Connections between Nonalcoholic Fatty Liver Disease, Steatohepatitis and Hepatocellular Carcinoma

Kanda, Tatsuo; Goto, Taichiro; Hirotsu, Yosuke; Masuzaki, Ryota; Moriyama, Mitsuhiko; Omata, Masao

doi:10.3390/ijms21041525

Cited by 71 publications

(58 citation statements)

References 114 publications

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“…Ultrasonic diagnosis criteria were (1) diffuse enhancement of near-field echo in the hepatic region (stronger than in the kidney and spleen region) and gradual attenuation of the far-field echo; (2) unclear display of the intra-hepatic lacuna structure; 3…”

Section: Supplementary Materialsmentioning

confidence: 99%

“…Nonalcoholic fatty liver disease (NAFLD) is characterized by hepatic lipid accumulation and is strongly associated with obesity, diabetes, and other features of the metabolic syndrome [1]. NAFLD has a wide spectrum ranging from hepatic steatosis to histological evidence of necroinflammation and nonalcoholic steatohepatitis (NASH), which may evolve into cirrhosis, final-stage liver disease, or hepatocellular carcinoma [2]. NAFLD has now been considered a serious worldwide health problem.…”

Section: Introductionmentioning

confidence: 99%

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The role of SAMM50 in non‐alcoholic fatty liver disease: from genetics to mechanisms

Shen

et al. 2021

FEBS Open Bio

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Nonalcoholic fatty liver disease (NAFLD) is characterized by hepatic lipid accumulation. SAMM50 encodes Sam50, a mitochondrial outer membrane protein involved in the removal of reactive oxygen species, mitochondrial morphology, and regulation of mitophagy. Certain single nucleotide polymorphisms (SNPs) of SAMM50 have been reported to be correlated with NAFLD. However, the contribution of SAMM50 polymorphisms to the occurrence and severity of fatty liver in the Chinese Han cohort has rarely been reported. Here, we investigated the association between SAMM50 polymorphisms (rs738491 and rs2073082) and NAFLD in a Chinese Han cohort, as well as the mechanistic basis of this association. Clinical information and blood samples were collected from 380 NAFLD cases and 380 normal subjects for the detection of genotypes and biochemical parameters. Carriers of the rs738491 T-allele or rs2073082 G-allele of SAMM50 exhibit increased susceptibility to NAFLD (OR=1.39; 95% CI=1.14-1.71, P=0.001; OR=1.31; 95% CI=1.05-1.62, P=0.016, respectively) and are correlated with elevated serum TG, ALT, and AST levels. The presence of the T allele (TT+CT) of rs738491 (P<0.01) or G allele (AG+GG) of rs2073082 (P=0.03) is correlated with the severity of fatty liver in the NAFLD cohort. In vitro studies indicated that SAMM50 gene polymorphisms decrease its expression and SAMM50 deficiency results in increased lipid

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Section: Supplementary Materialsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The role of SAMM50 in non‐alcoholic fatty liver disease: from genetics to mechanisms

Shen

et al. 2021

FEBS Open Bio

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“…A total of 5–20% of patients with steatosis will develop a more severe non-alcoholic steatohepatitis (NASH), which is characterized by liver inflammation, fibrosis, and tissue damage [ 4 ]. Patients with NASH who do not receive medical treatment and regulate their unhealthy lifestyle and eating habits will develop irreversible liver fibrosis, cirrhosis, liver failure, and liver cancer [ 5 ]. In addition, NAFLD is thought to increase the risk of cardiovascular disease (coronary atherosclerosis) [ 6 ].…”

Section: Introductionmentioning

confidence: 99%

Phloretin ameliorates hepatic steatosis through regulation of lipogenesis and Sirt1/AMPK signaling in obese mice

Liou

Shen

et al. 2020

Cell Biosci

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Background Phloretin is isolated from apple trees and could increase lipolysis in 3T3-L1 adipocytes. Previous studies have found that phloretin could prevent obesity in mice. In this study, we investigated whether phloretin ameliorates non-alcoholic fatty liver disease (NAFLD) in high-fat diet (HFD)-induced obese mice, and evaluated the regulation of lipid metabolism in hepatocytes. Methods HepG2 cells were treated with 0.5 mM oleic acid to induce lipid accumulation, and then treated with phloretin to evaluate the molecular mechanism of lipogenesis. In another experiment, male C57BL/6 mice were fed normal diet or HFD (60% fat, w/w) for 16 weeks. After the fourth week, mice were treated with or without phloretin by intraperitoneal injection for 12 weeks. Results Phloretin significantly reduced excessive lipid accumulation and decreased sterol regulatory element-binding protein 1c, blocking the expression of fatty acid synthase in oleic acid-induced HepG2 cells. Phloretin increased Sirt1, and phosphorylation of AMP activated protein kinase to suppress acetyl-CoA carboxylase expression, reducing fatty acid synthesis in hepatocytes. Phloretin also reduced body weight and fat weight compared to untreated HFD-fed mice. Phloretin also reduced liver weight and liver lipid accumulation and improved hepatocyte steatosis in obese mice. In liver tissue from obese mice, phloretin suppressed transcription factors of lipogenesis and fatty acid synthase, and increased lipolysis and fatty acid β-oxidation. Furthermore, phloretin regulated serum leptin, adiponectin, triglyceride, low-density lipoprotein, and free fatty acid levels in obese mice. Conclusions These findings suggest that phloretin improves hepatic steatosis by regulating lipogenesis and the Sirt-1/AMPK pathway in the liver.

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“…The recent advancements in sequencing technology are remarkable. Next-generation sequencers, the performance of which is several magnitudes higher than that of the sequencers used for human genome sequencing in the 1990s, have been put into practical use [15][16][17][18]. Combined with this technology, the data obtained using 16S rRNA gene sequencing and metagenomic analyses have become more comprehensible, faster, and less expensive, which has further boosted microbiome research.…”

Section: Microbiomes In the Lung And Bronchimentioning

confidence: 99%

Airway Microbiota as a Modulator of Lung Cancer

Goto

2020

IJMS

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Recent research on cancer-associated microbial communities has elucidated the interplay between bacteria, immune cells, and tumor cells; the bacterial pathways involved in the induction of carcinogenesis; and their clinical significance. Although accumulating evidence shows that a dysbiotic condition is associated with lung carcinogenesis, the underlying mechanisms remain unclear. Microorganisms possibly trigger tumor initiation and progression, presumably via the production of bacterial toxins and other pro-inflammatory factors. The purpose of this review is to discuss the basic role of the airway microbiome in carcinogenesis and the underlying molecular mechanisms, with the aim of developing anticancer strategies involving the airway microbiota. In addition, the mechanisms via which the microbiome acts as a modulator of immunotherapies in lung cancer are summarized.

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Molecular Mechanisms: Connections between Nonalcoholic Fatty Liver Disease, Steatohepatitis and Hepatocellular Carcinoma

Cited by 71 publications

References 114 publications

The role of SAMM50 in non‐alcoholic fatty liver disease: from genetics to mechanisms

The role of SAMM50 in non‐alcoholic fatty liver disease: from genetics to mechanisms

Phloretin ameliorates hepatic steatosis through regulation of lipogenesis and Sirt1/AMPK signaling in obese mice

Airway Microbiota as a Modulator of Lung Cancer

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