Dataset Information

Clinical characterization and proteomic profiling of lean nonalcoholic fatty liver disease

ABSTRACT: To investigate the proteomic features in lean subjects with NAFLD, and to identify possible plasma proteins that provide potential application for diagnosing of NAFLD in lean individuals. Participants with or without NAFLD were divided into an overweight NAFLD group, an overweight control group, a lean NAFLD group, and a lean control group according to body mass index. Samples of 20 subjects in each group were used for plasma proteomic profiling.

ORGANISM(S): Homo Sapiens

SUBMITTER: Cheng Hu

PROVIDER: PXD035514 | iProX | Thu Jul 21 00:00:00 BST 2022

REPOSITORIES: iProX

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Clinical characterization and proteomic profiling of lean nonalcoholic fatty liver disease.

Jiang Yuanye Y Zhuang Xiaoyu X Zhang Jiaqi J Li Meng M Du Shengnan S Tian Jiyun J Yuan Yifu Y Ji Guang G Hu Cheng C

Frontiers in endocrinology 20231116

<h4>Introduction</h4>Obesity has been historically associated with nonalcoholic fatty liver disease (NAFLD), but it can also occur in lean individuals. However, limited data is available on this special group. To investigate the clinical and proteomic characteristics of lean subjects with NAFLD, and to identify potential clinical variables and plasma proteins for diagnosing NAFLD in lean individuals, we collected clinical data from a large cohort of 2,236 subjects.<h4>Methods</h4>Diagnosis of NA ...[more]

PMID: 38034020

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Project description:Background & Aims: Overnutrition is one of the major causes of non-alcoholic fatty liver disease (NAFLD) and its advanced form non-alcoholic steatohepatitis (NASH). Besides the quantity of consumed calories, distinct dietary components are increasingly recognized as important contributor to the pathogenesis of NASH. We aimed to develop and characterize a hitherto missing murine model which resembles both the pathology and nutritional situation of NASH-patients in Western societies. Methods: We developed a NASH-inducing diet (ND) enriched with sucrose, cholesterol and a high concentration of fats rich in saturated fatty acids in a composition which mimics Western food. C57Bl6/N mice were fed with the ND or control chow for 12 weeks. Biochemical, real-time polymerase chain reaction, Western Blot and immunohistochemical analyses were performed to characterize systemic and hepatic changes induced by ND-feeding. Immunohistochemistry was used to assess c-Jun levels and activation in 110 human NAFLD and control liver specimens applying tissue micro array technology. Results: ND-fed mice showed significant body weight gain, impaired glucose tolerance, elevated fasting blood glucose levels as well as decreased adiponectin and increased leptin serum levels compared to control mice. In the liver, ND-feeding led to marked steatosis, enhanced cholesterol levels, distinct signs of oxidative stress, hepatocellular damage, inflammation, activation of hepatic stellate cells, and beginning fibrosis. Transcriptome-wide hepatic gene expression analysis comparing ND-fed mice and control mice indicated main alterations in lipid metabolism and inflammatory processes. Search for over-represented transcription factor target sites among the differentially expressed genes identified AP-1 as the most likely factor to cause the transcriptional changes in ND-livers. Combining differentially expressed gene and protein-protein interaction network analysis identified c-Jun (a component of the AP-1 complex) as hub in the largest connected deregulated sub-network in ND-livers. In accordance, ND-livers revealed c-Jun-phosphorylation and nuclear translocation. Moreover, hepatic c-Jun RNA and protein expression was enhanced in ND-fed compared to control mice. Also NAFLD-patients showed enhanced hepatic c-Jun levels, which correlated with inflammation, and notably, with the degree of hepatic steatosis. Conclusions: The new dietary mouse-model shows important pathological changes also found in human NASH and indicates c-jun/AP-1 activation as critical regulator of hepatic alterations. Abundance of c-jun in NAFLD likely facilitates development and progression of NASH, and thus, c-jun appears as attractive prognostic and therapeutic target of NAFLD progression. 14-weeks old male C57BL/6N mice were fed with either regular diet or a newly designed NASH-inducing diet for 12 weeks. Hepatic gene expression levels were measured thereafter.

Dataset Information

Clinical characterization and proteomic profiling of lean nonalcoholic fatty liver disease

Publications

Clinical characterization and proteomic profiling of lean nonalcoholic fatty liver disease.

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