Physiological Disturbance in Fatty Liver Energy Metabolism Converges on IGFBP2 Abundance and Regulation in Mice and Men

Fahlbusch, Pia; Knebel, Birgit; Hörbelt, Tina; Barbosa, David; Nikolic, Aleksandra; Shvero, Jacob; Al-Hasani, Hadi; Velde, Frederique Van de; Nieuwenhove, Yves Van; Müller‐Wieland, Dirk; Lapauw, Bruno; Ouwens, D.M.; Kotzka, Jörg

doi:10.3390/ijms21114144

Cited by 29 publications

(23 citation statements)

References 48 publications

(90 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…This observation is in line with human studies, as serum/plasma levels of IGFBP2 decreased in obese males and females and obese men with NAFLD and NASH compared with the non-obese control group [60,58]. Reduced level of IGFBP2 is along with decreased oxidation of fatty acids and enhanced de novo lipogenesis in hepatocytes [58].…”

Section: Discussionsupporting

confidence: 88%

“…The IGFBP2 promoter was hypermethylated, and its mRNA expression downregulated in a mouse model of fatty liver; therefore, secretion of hepatic IGFBP2 and plasma level of IGFBP2 reduced [58]. This observation is in line with human studies, as serum/plasma levels of IGFBP2 decreased in obese males and females and obese men with NAFLD and NASH compared with the non-obese control group [60,58]. Reduced level of IGFBP2 is along with decreased oxidation of fatty acids and enhanced de novo lipogenesis in hepatocytes [58].…”

Section: Discussionmentioning

confidence: 99%

“…IGFBPs are a family of secreted proteins binding to insulin-like growth factors (IGFs), regulating IGFs bioavailability and its function [57]. Recently evidence introduced this protein as a non-invasive biomarker for the development and pathogenesis of fatty liver disease [58,59]. The IGFBP2 promoter was hypermethylated, and its mRNA expression downregulated in a mouse model of fatty liver; therefore, secretion of hepatic IGFBP2 and plasma level of IGFBP2 reduced [58].…”

Section: Discussionmentioning

confidence: 99%

“…Recently evidence introduced this protein as a non-invasive biomarker for the development and pathogenesis of fatty liver disease [58,59]. The IGFBP2 promoter was hypermethylated, and its mRNA expression downregulated in a mouse model of fatty liver; therefore, secretion of hepatic IGFBP2 and plasma level of IGFBP2 reduced [58]. This observation is in line with human studies, as serum/plasma levels of IGFBP2 decreased in obese males and females and obese men with NAFLD and NASH compared with the non-obese control group [60,58].…”

Section: Discussionmentioning

confidence: 99%

See 3 more Smart Citations

Identification of Shared Gene Signatures in Different Stages of Non-Alcoholic Fatty Liver Disease Using Integrated Microarray Dataset

Gh¹,

Arabfard²

2020

Preprint

View full text Add to dashboard Cite

Purpose: Non-alcoholic fatty liver disease (NAFLD) is the most preventable type of chronic liver disease worldwide and a risk factor for developing cirrhosis or hepatocellular carcinoma (HCC) if untreated. Although experts have performed lots of efforts to find the underlying mechanisms of NAFLD, it remains a challenge to recognize them. The aim of this study is to distinguish common gene signature and pathways in the human liver during NAFLD progression through the systems biology method.Methods: In this study, the three microarray datasets, GSE48452, GSE63067 and GSE89632, were selected from the NCBI GEO database to explore differentially expressed genes (DEGs) among healthy controls, simple steatosis and non-alcoholic steatohepatitis (NASH) patients. Furthermore, protein-protein interaction (PPI) networks and pathway enrichment analysis were used to detect common genes and biological pathways in different stages of NAFLD.Results: The current study was included 47 healthy subjects, 36 patients with simple steatosis and 46 NASH patients. Common high degree genes among all three sets were CHI3L1, GFBP2, NRG1, PEG10 and FADS2. The top five genes in the hepatic PPI networks of three datasets were STAT3, JUN, CANX, FN1 and MYC. Signal transduction, immune response, and anti-apoptosis were the most important biological pathways between healthy vs. NASH, while cell communication, signal transduction and immune response were three top biological pathways between healthy vs. simple steatosis. Also, the most eminent biological pathways between NASH vs. simple steatosis were metabolism and energy pathways. Conclusion: The present study represented the unique and shared key genes and pathways between different stages of NAFLD, which may facilitate the understanding of the NAFLD mechanism and identify potential therapeutic targets in this disease.

show abstract

Section: Discussionsupporting

confidence: 88%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Identification of Shared Gene Signatures in Different Stages of Non-Alcoholic Fatty Liver Disease Using Integrated Microarray Dataset

Gh¹,

Arabfard²

2020

Preprint

View full text Add to dashboard Cite

show abstract

“…These results are also supported by a recent cohort study indicating that IGFBP2 levels are inversely associated with the risk of NAFLD [ 91 ]. Similarly, Fahlbusch et al demonstrated that circulating levels of IGFBP2 are lower in patients with NAFLD and NASH, and are restored after weight loss following bariatric surgery along with reductions in hepatic fat content [ 92 ]. A recent epigenomic study suggested that differentially methylated genes might distinguish patients with advanced NASH from simple steatosis [ 93 ].…”

Section: Epigenetic Mechanisms Underlying the Link Between Nutrition And Aberrant Gene Expression In Nafldmentioning

confidence: 99%

Dietary Patterns Influence Target Gene Expression through Emerging Epigenetic Mechanisms in Nonalcoholic Fatty Liver Disease

et al. 2021

View full text Add to dashboard Cite

Nonalcoholic fatty liver disease (NAFLD) refers to the pathologic buildup of extra fat in the form of triglycerides in liver cells without excessive alcohol intake. NAFLD became the most common cause of chronic liver disease that is tightly associated with key aspects of metabolic disorders, including insulin resistance, obesity, diabetes, and metabolic syndrome. It is generally accepted that multiple mechanisms and pathways are involved in the pathogenesis of NAFLD. Heredity, sedentary lifestyle, westernized high sugar saturated fat diet, metabolic derangements, and gut microbiota, all may interact on a on genetically susceptible individual to cause the disease initiation and progression. While there is an unquestionable role for gene-diet interaction in the etiopathogenesis of NAFLD, it is increasingly apparent that epigenetic processes can orchestrate many aspects of this interaction and provide additional mechanistic insight. Exciting research demonstrated that epigenetic alterations in chromatin can influence gene expression chiefly at the transcriptional level in response to unbalanced diet, and therefore predispose an individual to NAFLD. Thus, further discoveries into molecular epigenetic mechanisms underlying the link between nutrition and aberrant hepatic gene expression can yield new insights into the pathogenesis of NAFLD, and allow innovative epigenetic-based strategies for its early prevention and targeted therapies. Herein, we outline the current knowledge of the interactive role of a high-fat high-calories diet and gene expression through DNA methylation and histone modifications on the pathogenesis of NAFLD. We also provide perspectives on the advancement of the epigenomics in the field and possible shortcomings and limitations ahead.

show abstract

Transcriptomic profiling of a multiethnic pediatric NAFLD cohort reveals genes and pathways associated with disease

et al. 2022

View full text Add to dashboard Cite

Nonalcoholic fatty liver disease (NAFLD) is the most common type of chronic liver disease in children. The mechanisms that drive NAFLD disease progression in this specific patient population remain poorly defined. In this study, we obtained liver biopsy samples from a multiethnic cohort of pediatric patients with NAFLD (n = 52, mean age = 13.6 years) and healthy liver controls (n = 5). We analyzed transcriptomic changes associated with NAFLD stages using high-throughput RNA sequencing. Unsupervised clustering as well as pairwise transcriptome comparison distinguished NAFLD from healthy livers.We identified perturbations in pathways including calcium and insulin/glucose signaling occurring early in NAFLD disease, before the presence of histopathologic evidence of advanced disease. Transcriptomic comparisons identified a 25-gene signature associated with the degree of liver fibrosis. We also identified expression of the insulin-like growth factor binding protein (IGFBP) gene family (1/2/3/7) as correlating with disease stages, and it has the potential to be used as a peripheral biomarker in NAFLD. Comparing our data set with publicly available adult and adolescent transcriptomic data, we identified similarities and differences in pathway enrichment and gene-expression profiles between adult and pediatric patients with NAFLD. Regulation of genes including interleukin-32, IGFBP1, IGFBP2, and IGFBP7 was consistently

show abstract

Physiological Disturbance in Fatty Liver Energy Metabolism Converges on IGFBP2 Abundance and Regulation in Mice and Men

Cited by 29 publications

References 48 publications

Identification of Shared Gene Signatures in Different Stages of Non-Alcoholic Fatty Liver Disease Using Integrated Microarray Dataset

Identification of Shared Gene Signatures in Different Stages of Non-Alcoholic Fatty Liver Disease Using Integrated Microarray Dataset

Dietary Patterns Influence Target Gene Expression through Emerging Epigenetic Mechanisms in Nonalcoholic Fatty Liver Disease

Transcriptomic profiling of a multiethnic pediatric NAFLD cohort reveals genes and pathways associated with disease

Contact Info

Product

Resources

About