What is it about?

Obesity (OB) is one of the major risk factors of non-alcoholic fatty liver disease (NAFLD), however, the reliable diagnostic markers are not fully known. The purpose of this study is to clarify the shared pathophysiological diagnostic markers of OB and NAFLD. We analyzed mRNA expression profiles of NAFLD and OB from the GEO database using WGCNA to identify gene modules. Lasso regression and ROC curve helped construct predictive models. Key genes were examined for function via multiple analyses, including in vivo experiments and immune infiltration. BBOX1, SSTR1, MMP7, and LACC1 emerged as common predictors for OB and NAFLD through animal experimentation and predictive model analysis.

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Why is it important?

Obesity is defined as abnormal or excessive body fat accumulation leading to impairment of health. Representing a worldwide major health challenge, OB is associated with the decrease in life expectancy and is correlated with many metabolic diseases including liver disease and insulin resistance. The prevalence of NAFLD among adults worldwide is about one-fourth. With 20% of individuals developing cirrhosis, NAFLD has been linked to higher risks of both overall and liver-specific mortality1. OB is one of the main risk factors of NAFLD, which is correlated with pro-inflammatory factors such as IL-1 and TNF. Over time, hepatic fat accumulation is promoted by a synergistic interaction between hepatic lipid dysregulation, oxidative stress, and pro-inflammatory cytokines, which results in the development of NAFLD2. However, critical steps and valid diagnostic markers in the disease progress are incompletely understood. Therefore, our study constructed and evaluated the predictive models, consisting of four key genes for NAFLD and OB that were elucidated from the GEO database, to further explore the mechanism between NAFLD and OB as well as to offer new ideas for clinical treatment.

Perspectives

In summary, BBOX1, SSTR1, MMP7, and LACC1 are identified as diagnostic markers of OB and NAFLD. Our clinical prediction model and in vivo experiments in mice confirm that these four genes are common predictors for OB and NAFLD, and they likely play crucial roles in the development and onset of the diseases. Consequently, further research is necessary to explore the interplay between drug treatments and gene expression, potentially paving the way for new clinical treatment strategies.

Yiyuan Zheng

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This page is a summary of: BBOX1, LACC1, MMP7 and SSTR1 as common predictors in obesity and non-alcoholic fatty liver disease, Genes & Diseases, March 2025, Tsinghua University Press,
DOI: 10.1016/j.gendis.2024.101310.
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