Berry intake changes hepatic gene expression and DNA methylation patterns associated with high-fat diet

Area of Science:

• Metabolic health
• Nutritional science
• Molecular biology

Background:

• Fatty liver disease is linked to obesity and insulin resistance.
• Berries show differential effects on hepatic steatosis and obesity in mice.
• Previous studies identified protective effects of lingonberries and bilberries, and exacerbating effects of açai berries.

Purpose of the Study:

• Investigate the underlying mechanisms of berry-induced effects on hepatic steatosis.
• Identify key molecular pathways and regulators involved in these berry-specific effects.
• Explore the role of gene expression and DNA methylation in berry-mediated metabolic changes.

Main Methods:

• High-fat diet-fed C57BL/6J mouse model.
• Genome-wide hepatic gene expression profiling.
• In silico transcription factor analysis and immunoblot analysis.
• HELP-tagging assay for CpG methylation analysis.

Main Results:

• Lingonberries and bilberries downregulated inflammatory genes (e.g., Saa1, Cxcl1, Lcn2).
• Açai berries upregulated steatosis and lipid/cholesterol biosynthesis genes (e.g., Cfd, Cidea, Crat).
• NF-κB, STAT3, and mTOR were identified as upstream regulators.
• Lingonberries induced genome-wide and specific Ncor2 hypermethylation.

Conclusions:

• Beneficial effects of lingonberries and bilberries involve downregulation of inflammatory pathways.
• Mechanisms for blackcurrant effects differ from lingonberries and bilberries.
• NF-κB, STAT3, and mTOR are potential targets for berry-mediated health benefits.