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

Lovisa Heyman-Lindén, Yoshinori Seki, Petter Storm, Helena A. Jones, Maureen J. Charron, Karin Berger, Cecilia Holm

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

The liver is a critical organ for regulation of energy homeostasis and fatty liver disease is closely associated with obesity and insulin resistance. We have previously found that lingonberries, blackcurrants and bilberries prevent, whereas açai berries exacerbate, the development of hepatic steatosis and obesity in the high-fat (HF)-fed C57BL/6J mouse model. In this follow-up study, we investigated the mechanisms behind these effects. Genome-wide hepatic gene expression profiling indicates that the protective effects of lingonberries and bilberries are accounted for by several-fold downregulation of genes involved in acute-phase and inflammatory pathways (e.g. Saa1, Cxcl1, Lcn2). In contrast, açai-fed mice exhibit marked upregulation of genes associated with steatosis (e.g. Cfd, Cidea, Crat) and lipid and cholesterol biosynthesis, which is in line with the exacerbation of HF-induced hepatic steatosis in these mice. In silico transcription factor analysis together with immunoblot analysis identified NF-κB, STAT3 and mTOR as upstream regulators involved in mediating the observed transcriptional effects. To gain further insight into mechanisms involved in the gene expression changes, the HELP-tagging assay was used to identify differentially methylated CpG sites. Compared to the HF control group, lingonberries induced genome-wide hypermethylation and specific hypermethylation of Ncor2, encoding the corepressor NCoR/SMRT implicated in the regulation of pathways of metabolic homeostasis and inflammation. We conclude that the beneficial metabolic effects of lingonberries and bilberries are associated with downregulation of inflammatory pathways, whereas for blackcurrants, exerting similar metabolic effects, different mechanisms of action appear to dominate. NF-κB, STAT3 and mTOR are potential targets of the health-promoting effects of berries.

Original languageEnglish (US)
Pages (from-to)79-95
Number of pages17
JournalJournal of Nutritional Biochemistry
Volume27
DOIs
StatePublished - Jan 1 2016

Fingerprint

Vaccinium vitis-idaea
Vaccinium myrtillus
High Fat Diet
DNA Methylation
Nutrition
Gene expression
Fruit
Genes
Fats
Gene Expression
Liver
Homeostasis
Down-Regulation
Obesity
Genome
Co-Repressor Proteins
Biosynthesis
Gene Expression Profiling
Factor analysis
Fatty Liver

Keywords

  • Berries
  • Gene expression
  • High-fat diet
  • Inflammation
  • Liver steatosis
  • Methylation

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Molecular Biology
  • Endocrinology, Diabetes and Metabolism
  • Nutrition and Dietetics

Cite this

Berry intake changes hepatic gene expression and DNA methylation patterns associated with high-fat diet. / Heyman-Lindén, Lovisa; Seki, Yoshinori; Storm, Petter; Jones, Helena A.; Charron, Maureen J.; Berger, Karin; Holm, Cecilia.

In: Journal of Nutritional Biochemistry, Vol. 27, 01.01.2016, p. 79-95.

Research output: Contribution to journalArticle

Heyman-Lindén, Lovisa ; Seki, Yoshinori ; Storm, Petter ; Jones, Helena A. ; Charron, Maureen J. ; Berger, Karin ; Holm, Cecilia. / Berry intake changes hepatic gene expression and DNA methylation patterns associated with high-fat diet. In: Journal of Nutritional Biochemistry. 2016 ; Vol. 27. pp. 79-95.
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