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Paternal high‐fat diet transgenerationally impacts hepatic immunometabolism
Author(s) -
Castro Barbosa Thais,
Alm Petter S.,
Krook Anna,
Barrès Romain,
Zierath Juleen R.
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.201801879rr
Subject(s) - offspring , transcriptome , biology , endocrinology , medicine , downregulation and upregulation , gene , basal (medicine) , gene expression , genetics , insulin , pregnancy
Paternal preconceptional high‐fat diet (HFD) alters whole‐body glucose and energy homeostasis over several generations, which may be mediated by altered transcriptomic profiles of metabolic organs. We investigated the effect of paternal HFD on the hepatic transcriptomic and metabolic signatures of female grand‐offspring. Paternal HFD strongly impacted the liver transcriptome of the second‐generation offspring. Gene set enrichment analysis (GSEA) revealed grandpaternal‐HFD altered the TNF‐α signaling via NFκB pathway, independent of the grand‐offspring's diet. Reduction in the hepatic cytokine levels, including the TNF‐α, as well as NFκB content and activity, suggest that the basal inflammatory response in F2 rats is disturbed. GSEA also show altered expression of various genes annotated to the fatty acid metabolism. Grandpaternal‐HFD reduced G 0 /G 1 switch gene 2 ( G0S2 ) expression, concomitant with reduced hepatic triglyceride content in F2 rats. In conclusion, the hepatic transcriptome is altered in grand‐offspring from HFD‐fed grandfathers. Altered TNF‐α/NFκB signaling and levels of inflammatory cytokines indicate grand‐paternal HFD impacts hepatic immunometabolism. Overall, our findings indicate that paternal exposure to environmental factors transgenerationally reprograms metabolism in a tissue‐specific manner, affecting the development and health of future generations.—De Castro Barbosa, T., Alm, P. S., Krook, A., Barrès, R., Zierath, J. R. Paternal high‐fat diet transgenerationally impacts hepatic immunometabolism. FASEB J. 33, 6269–6280 (2019). www.fasebj.org