Identification of transcriptomic signatures and crucial pathways involved in non-alcoholic steatohepatitis

He, Wei; Huang, Caoxin; Zhang, Xiaofang; Wang, Dongmei; Chen, Yin-ling; Zhao, Yan; Li, Xuejun

doi:10.1007/s12020-021-02716-y

Cited by 21 publications

(21 citation statements)

References 60 publications

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“…Among the most studied adipokines released from white adipose tissue are adiponectin, leptin, resistin, plasminogen activator inhibitor-1 (PAI-1), and tumor necrosis factor α (TNFα). Additionally, FABP4 has been proposed as a potential biomarker/causal agent for ectopic fat deposition in non-adipose tissues [ 58 ], including the liver [ 18 , 20 , 21 , 22 , 23 , 24 , 25 , 30 , 59 , 60 , 61 , 62 , 63 ].…”

Section: Etiopathogenesis Of Mafld: Role Of White Adipose Tissuementioning

confidence: 99%

“…FABP4, also termed adipocyte FABP (A-FABP) or adipocyte P2 (aP2), is an intracellular lipid-binding protein mainly expressed in adipocytes [ 64 ], but also in macrophages [ 65 ], and dendritic [ 66 ] and endothelial cells [ 67 ] to a lesser extent. Additionally, the FABP4 gene expression has been found to be upregulated in the livers of morbidly obese patients in the context of insulin resistance [ 68 ] and in patients with different MAFLD severities [ 59 , 60 , 61 , 62 , 63 ].…”

Section: Fatty Acid Binding Proteinmentioning

confidence: 99%

“…Actually, the FABP4 expression was higher in visceral adipose tissue from MASH than non-MASH patients [ 115 ]. Additionally, FABP4 mRNA levels were found to be upregulated in the livers from MASH patients [ 61 , 62 , 63 ], and it has been proposed as an efficient classifier of mild-MAFL and MASH [ 63 ]. Moreover, a high liver expression of FABP4 has been associated with increased risk for progression to MASH [ 59 ].…”

Section: Fabp4 As Potential Biomarker For Mafldmentioning

confidence: 99%

“…It has been proposed that FABP4 is able to integrate both metabolic and immune responses to link inflammatory and lipid-mediated pathways [ 124 ]. FABP4 was found to be one of the top 10 up-regulated genes in a transcriptome signature study performed in MASH patients [ 62 ], suggesting a relevant role not only for liver fat deposition, but also for MASH progression. The liver expression of FABP4 was reduced in the absence of cathepsin B, a cysteine protease found to be upregulated in the livers of MASH mice, supporting its role as an active player in the disease [ 125 ].…”

Section: Fabp4 As Active Player In the Mafldmentioning

confidence: 99%

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Unveiling the Role of the Fatty Acid Binding Protein 4 in the Metabolic-Associated Fatty Liver Disease

et al. 2022

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Metabolic-associated fatty liver disease (MAFLD), the main cause of chronic liver disease worldwide, is a progressive disease ranging from fatty liver to steatohepatitis (metabolic-associated steatohepatitis; MASH). Nevertheless, it remains underdiagnosed due to the lack of effective non-invasive methods for its diagnosis and staging. Although MAFLD has been found in lean individuals, it is closely associated with obesity-related conditions. Adipose tissue is the main source of liver triglycerides and adipocytes act as endocrine organs releasing a large number of adipokines and pro-inflammatory mediators involved in MAFLD progression into bloodstream. Among the adipocyte-derived molecules, fatty acid binding protein 4 (FABP4) has been recently associated with fatty liver and additional features of advanced stages of MAFLD. Additionally, emerging data from preclinical studies propose FABP4 as a causal actor involved in the disease progression, rather than a mere biomarker for the disease. Therefore, the FABP4 regulation could be considered as a potential therapeutic strategy to MAFLD. Here, we review the current knowledge of FABP4 in MAFLD, as well as its potential role as a therapeutic target for this disease.

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Section: Etiopathogenesis Of Mafld: Role Of White Adipose Tissuementioning

confidence: 99%

Section: Fatty Acid Binding Proteinmentioning

confidence: 99%

Section: Fabp4 As Potential Biomarker For Mafldmentioning

confidence: 99%

Section: Fabp4 As Active Player In the Mafldmentioning

confidence: 99%

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Unveiling the Role of the Fatty Acid Binding Protein 4 in the Metabolic-Associated Fatty Liver Disease

et al. 2022

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“…Furthermore, FLI was reported to be positively associated with FABP4 level 42,43 , which was confirmed in the present study. Transcriptome analyses showed that FABP4 in the liver is upregulated in patients with NAFLD 44 and patients with non-alcoholic steatohepatitis 45 , and that FABP4 is a predictive factor for poor prognosis in patients with NAFLD 46 . Therefore, it is possible that modulations of FABP4 might contribute to the prognosis of MAFLD and its related metabolic and cardiovascular diseases in humans.…”

Section: Discussionmentioning

confidence: 99%

Circulating level of fatty acid‐binding protein 4 is an independent predictor of metabolic dysfunction‐associated fatty liver disease in middle‐aged and elderly individuals

Tanaka

Takahashi

Higashiura

et al. 2022

J of Diabetes Invest

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Aims/Introduction Metabolic dysfunction‐associated fatty liver disease (MAFLD), defined as hepatosteatosis with type 2 diabetes mellitus, overweight/obesity or metabolic dysregulation, has been proposed as a new feature of chronic liver disease. Fatty acid‐binding protein 4 (FABP4) is expressed in adipose tissue, and secreted FABP4 is associated with the development of insulin resistance and atherosclerosis. However, the relationship between MAFLD and FABP4 has not been fully addressed. Materials and Methods Associations of MAFLD with metabolic markers, including FABP4, fibroblast growth factor 21 and adiponectin, were investigated in 627 individuals (men/women 292/335) in the Tanno‐Sobetsu Study, a population‐based cohort. Results The mean age was 65 years (range 19–98 years, median [interquartile range] 68 [56–76] years). Hepatosteatosis was determined by the fatty liver index (FLI), and FLI ≥35 for men and FLI ≥16 for women were used for detection of fatty liver, as previously reported using 14,471 Japanese individuals. FLI was positively correlated with systolic blood pressure and levels of FABP4 (r = 0.331, P < 0.001), fibroblast growth factor 21, homeostasis model assessment of insulin resistance as an insulin resistance index and uric acid, and was negatively correlated with levels of high‐density lipoprotein cholesterol and adiponectin. FABP4 concentration was independently associated with FLI after adjustment of age, sex, systolic blood pressure and levels of uric acid, high‐density lipoprotein cholesterol, homeostasis model assessment of insulin resistance, adiponectin and fibroblast growth factor 21 in multivariable regression analysis. Logistic regression analysis showed that FABP4 was an independent predictor of MAFLD after adjustment of age, sex, presence of diabetes mellitus, hypertension and dyslipidemia, and levels of uric acid, homeostasis model assessment of insulin resistance, adiponectin and fibroblast growth factor 21. Conclusions FABP4 concentration is independently associated with FLI and is an independent predictor of MAFLD in middle‐aged and elderly individuals.

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Hydrodynamic Injection for Developing NASH Model

Wang

2022

Methods in Molecular Biology

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Identification of transcriptomic signatures and crucial pathways involved in non-alcoholic steatohepatitis

Cited by 21 publications

References 60 publications

Unveiling the Role of the Fatty Acid Binding Protein 4 in the Metabolic-Associated Fatty Liver Disease

Unveiling the Role of the Fatty Acid Binding Protein 4 in the Metabolic-Associated Fatty Liver Disease

Circulating level of fatty acid‐binding protein 4 is an independent predictor of metabolic dysfunction‐associated fatty liver disease in middle‐aged and elderly individuals

Hydrodynamic Injection for Developing NASH Model

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