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The expression levels of the hepatic Morc4 associated with hepatic lipid metabolism phenotypes. (A) hepatic Morc4 expression levels across 41 BXD mouse strains. (B) Manhattan plots from ePWAS emphasizing the metabolic phenotypes associated with Morc4 expression in BXD mice. Each point represents a distinct metabolic phenotype, with the red horizontal line denoting the threshold for statistical significance (log10 p > 2). (C,D) Scatterplots depicting the correlation between Morc4 expression and plasma lipid metabolism levels in the liver of BXD mice. Each point corresponds to an individual BXD strain. Pearson correlation coefficients were calculated to evaluate the relationship.

Journal: Frontiers in Cardiovascular Medicine

Article Title: Morc4 is a novel functional gene associated with lipid metabolism in BXD recombinant inbred population

doi: 10.3389/fcvm.2025.1570729

Figure Lengend Snippet: The expression levels of the hepatic Morc4 associated with hepatic lipid metabolism phenotypes. (A) hepatic Morc4 expression levels across 41 BXD mouse strains. (B) Manhattan plots from ePWAS emphasizing the metabolic phenotypes associated with Morc4 expression in BXD mice. Each point represents a distinct metabolic phenotype, with the red horizontal line denoting the threshold for statistical significance (log10 p > 2). (C,D) Scatterplots depicting the correlation between Morc4 expression and plasma lipid metabolism levels in the liver of BXD mice. Each point corresponds to an individual BXD strain. Pearson correlation coefficients were calculated to evaluate the relationship.

Article Snippet: The lipid metabolism-related phenotype data in Morc4 knockout mice were obtained from the International Mouse Phenotyping Consortium (IMPC) ( https://www.mousephenotype.org/ ).

Techniques: Expressing, Clinical Proteomics

The role of MORC4 on lipid metabolism in THLE-2 and HepG2 cells. The knockdown and overexpression of MORC4 in THLE-2 cells (A) and HepG2 cells (C) were analyzed using qPCR experiment. The total cholesterol (TC) and triglyceride (TG) levels following MOCR4 knockdown and overexpression in THLE-2 cells (B) and HepG2 cells (D) were measured by assay kits. The accumulation of lipid droplets in THLE-2 cells (E) and HepG2 cells (F) after MOCR4 knockdown and overexpression were detected with Oil Red O staining. OA, oleic acid; * P < 0.05, ** P < 0.01, *** P < 0.001; n = 3.

Journal: Frontiers in Cardiovascular Medicine

Article Title: Morc4 is a novel functional gene associated with lipid metabolism in BXD recombinant inbred population

doi: 10.3389/fcvm.2025.1570729

Figure Lengend Snippet: The role of MORC4 on lipid metabolism in THLE-2 and HepG2 cells. The knockdown and overexpression of MORC4 in THLE-2 cells (A) and HepG2 cells (C) were analyzed using qPCR experiment. The total cholesterol (TC) and triglyceride (TG) levels following MOCR4 knockdown and overexpression in THLE-2 cells (B) and HepG2 cells (D) were measured by assay kits. The accumulation of lipid droplets in THLE-2 cells (E) and HepG2 cells (F) after MOCR4 knockdown and overexpression were detected with Oil Red O staining. OA, oleic acid; * P < 0.05, ** P < 0.01, *** P < 0.001; n = 3.

Article Snippet: The lipid metabolism-related phenotype data in Morc4 knockout mice were obtained from the International Mouse Phenotyping Consortium (IMPC) ( https://www.mousephenotype.org/ ).

Techniques: Knockdown, Over Expression, Measured Assay, Staining

The relationship between Morc4 and cholesterol metabolism pathways. The GO enrichment bubble plot (A) and KEGG enrichment bubble plot (B) of the top 2,000 genes related to Morc4.The x -axis represents the enrichment ratio, the y -axis lists the GO terms, the bubble size reflects the gene count, and the color indicates the FDR value. (C) The protein-protein interaction (PPI) network related to the cholesterol metabolism pathway highlights genes with an interaction score greater than 0.4 (indicating moderate confidence), (D) sourced from the STRING database ( https://www.string-db.org/ ). In the cholesterol metabolism pathway, Morc4 shows significant correlations with eight key lipid metabolism genes, with negative correlations shown in blue and positive correlations shown in red. (E–L) A scatter plot of the correlation between these eight genes and MORC4 is provided, along with the correlation coefficient (r) and corresponding p -values for each plot.

Journal: Frontiers in Cardiovascular Medicine

Article Title: Morc4 is a novel functional gene associated with lipid metabolism in BXD recombinant inbred population

doi: 10.3389/fcvm.2025.1570729

Figure Lengend Snippet: The relationship between Morc4 and cholesterol metabolism pathways. The GO enrichment bubble plot (A) and KEGG enrichment bubble plot (B) of the top 2,000 genes related to Morc4.The x -axis represents the enrichment ratio, the y -axis lists the GO terms, the bubble size reflects the gene count, and the color indicates the FDR value. (C) The protein-protein interaction (PPI) network related to the cholesterol metabolism pathway highlights genes with an interaction score greater than 0.4 (indicating moderate confidence), (D) sourced from the STRING database ( https://www.string-db.org/ ). In the cholesterol metabolism pathway, Morc4 shows significant correlations with eight key lipid metabolism genes, with negative correlations shown in blue and positive correlations shown in red. (E–L) A scatter plot of the correlation between these eight genes and MORC4 is provided, along with the correlation coefficient (r) and corresponding p -values for each plot.

Article Snippet: The lipid metabolism-related phenotype data in Morc4 knockout mice were obtained from the International Mouse Phenotyping Consortium (IMPC) ( https://www.mousephenotype.org/ ).

Techniques:

The role of MORC4 in regulating the expression levels of lipid metabolism-related genes. After changes in MORC4 expression levels, alterations in the expression of lipid metabolism-related genes in THLE-2 cells (A) and HepG2 cells (B) were observed. * P < 0.05, ** P < 0.01, *** P < 0.001; n = 3.

Journal: Frontiers in Cardiovascular Medicine

Article Title: Morc4 is a novel functional gene associated with lipid metabolism in BXD recombinant inbred population

doi: 10.3389/fcvm.2025.1570729

Figure Lengend Snippet: The role of MORC4 in regulating the expression levels of lipid metabolism-related genes. After changes in MORC4 expression levels, alterations in the expression of lipid metabolism-related genes in THLE-2 cells (A) and HepG2 cells (B) were observed. * P < 0.05, ** P < 0.01, *** P < 0.001; n = 3.

Article Snippet: The lipid metabolism-related phenotype data in Morc4 knockout mice were obtained from the International Mouse Phenotyping Consortium (IMPC) ( https://www.mousephenotype.org/ ).

Techniques: Expressing

Alterations in lipid metabolism phenotypes following Morc4 knockout in IMPC database. The residuals of whole-body lipid metabolism-related traits were adjusted for genotype and sex in mice that are heterozygous for a Morc4 gene-trap allele. (A) Body weight, (B) Fat mass, (C) Fat/body weight ratio, (D) Lean/body weight ratio, (E) Total cholesterol, (F) Cholesterol ratio, (G) Proposed model illustrating that MORC4 regulates hepatic lipid metabolism. The downregulation of Morc4 expression leads to reduced uptake of free fatty acids/cholesterol, as well as a decrease in triglyceride hydrolysis, while concurrently enhancing cholesterol synthesis. This interplay contributes to the dysfunction of lipid metabolism.

Journal: Frontiers in Cardiovascular Medicine

Article Title: Morc4 is a novel functional gene associated with lipid metabolism in BXD recombinant inbred population

doi: 10.3389/fcvm.2025.1570729

Figure Lengend Snippet: Alterations in lipid metabolism phenotypes following Morc4 knockout in IMPC database. The residuals of whole-body lipid metabolism-related traits were adjusted for genotype and sex in mice that are heterozygous for a Morc4 gene-trap allele. (A) Body weight, (B) Fat mass, (C) Fat/body weight ratio, (D) Lean/body weight ratio, (E) Total cholesterol, (F) Cholesterol ratio, (G) Proposed model illustrating that MORC4 regulates hepatic lipid metabolism. The downregulation of Morc4 expression leads to reduced uptake of free fatty acids/cholesterol, as well as a decrease in triglyceride hydrolysis, while concurrently enhancing cholesterol synthesis. This interplay contributes to the dysfunction of lipid metabolism.

Article Snippet: The lipid metabolism-related phenotype data in Morc4 knockout mice were obtained from the International Mouse Phenotyping Consortium (IMPC) ( https://www.mousephenotype.org/ ).

Techniques: Knock-Out, Expressing