TY - JOUR
T1 - Paternal high-fat diet transgenerationally impacts hepatic immunometabolism
AU - Barbosa, Thais de Castro
AU - Alm, Petter S.
AU - Krook, Anna
AU - Barrès, Romain
AU - Zierath, Juleen R.
PY - 2019/5/1
Y1 - 2019/5/1
N2 - 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 G0/G1 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.
AB - 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 G0/G1 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.
KW - metabolism
KW - epigenetics
KW - cytokines
KW - liver
U2 - 10.1096/fj.201801879rr
DO - 10.1096/fj.201801879rr
M3 - Journal article
C2 - 30768368
SN - 0892-6638
VL - 33
SP - 6269
EP - 6280
JO - FASEB Journal
JF - FASEB Journal
IS - 5
ER -