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Metabolic gene expression and epigenetic effects of the ketone body β-hydroxybutyrate on H3K9ac in bovine cells, oocytes and embryos.
Sci Rep 2018; 8(1):13766SR

Abstract

The rapid decline in fertility that has been occurring to high-producing dairy cows in the past 50 years seems to be associated with metabolic disturbances such as ketosis, supporting the need for research to improve our understanding of the relations among the diet, metabolism and embryonic development. Recently, the ketone body β-hydroxybutyrate (BOHB) was demonstrated to be a potent inhibitor of histone deacetylases (HDACs). Herein, we performed a series of experiments aiming to investigate the epigenetic effects of BOHB on histone acetylation in somatic cells, cumulus-oocyte complexes (COCs) and somatic cell nuclear transfer (SCNT) embryos. Treatment with BOHB does not increase histone acetylation in cells but stimulates genes associated with ketolysis and master regulators of metabolism. We further demonstrated that maturing COCs with high levels of BOHB does not affect their maturation rate or histone acetylation but increases the expression of PPARA in cumulus cells. Treatment of somatic cell nuclear transfer zygotes with BOHB causes hyperacetylation, which is maintained until the blastocyst stage, causing enhanced FOXO3A expression and blastocyst production. Our data shed light on the epigenetic mechanisms caused by BOHB in bovine cells and embryos and provide a better understanding of the connection between nutrition and reproduction.

Authors+Show Affiliations

University of Sao Paulo, Department of Veterinary Medicine, Faculty of Animal Science and Food Engineering, Pirassununga, Sao Paulo, postcode: 13635-900, Brazil. julianors@usp.br.University of Sao Paulo, Department of Veterinary Medicine, Faculty of Animal Science and Food Engineering, Pirassununga, Sao Paulo, postcode: 13635-900, Brazil.University of Sao Paulo, Department of Veterinary Medicine, Faculty of Animal Science and Food Engineering, Pirassununga, Sao Paulo, postcode: 13635-900, Brazil.University of Sao Paulo, Department of Veterinary Medicine, Faculty of Animal Science and Food Engineering, Pirassununga, Sao Paulo, postcode: 13635-900, Brazil.University of Sao Paulo, Department of Veterinary Medicine, Faculty of Animal Science and Food Engineering, Pirassununga, Sao Paulo, postcode: 13635-900, Brazil.University of Sao Paulo, Department of Veterinary Medicine, Faculty of Animal Science and Food Engineering, Pirassununga, Sao Paulo, postcode: 13635-900, Brazil.Université de Montréal, Faculté de médecine vétérinaire, Centre de recherche en reproduction et fertilité, St. Hyacinthe, Québec, postcode: H3T 1J4, Canada.University of Sao Paulo, Department of Veterinary Medicine, Faculty of Animal Science and Food Engineering, Pirassununga, Sao Paulo, postcode: 13635-900, Brazil.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

30214009

Citation

Sangalli, Juliano Rodrigues, et al. "Metabolic Gene Expression and Epigenetic Effects of the Ketone Body Β-hydroxybutyrate On H3K9ac in Bovine Cells, Oocytes and Embryos." Scientific Reports, vol. 8, no. 1, 2018, p. 13766.
Sangalli JR, Sampaio RV, Del Collado M, et al. Metabolic gene expression and epigenetic effects of the ketone body β-hydroxybutyrate on H3K9ac in bovine cells, oocytes and embryos. Sci Rep. 2018;8(1):13766.
Sangalli, J. R., Sampaio, R. V., Del Collado, M., da Silveira, J. C., De Bem, T. H. C., Perecin, F., ... Meirelles, F. V. (2018). Metabolic gene expression and epigenetic effects of the ketone body β-hydroxybutyrate on H3K9ac in bovine cells, oocytes and embryos. Scientific Reports, 8(1), p. 13766. doi:10.1038/s41598-018-31822-7.
Sangalli JR, et al. Metabolic Gene Expression and Epigenetic Effects of the Ketone Body Β-hydroxybutyrate On H3K9ac in Bovine Cells, Oocytes and Embryos. Sci Rep. 2018 09 13;8(1):13766. PubMed PMID: 30214009.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Metabolic gene expression and epigenetic effects of the ketone body β-hydroxybutyrate on H3K9ac in bovine cells, oocytes and embryos. AU - Sangalli,Juliano Rodrigues, AU - Sampaio,Rafael Vilar, AU - Del Collado,Maite, AU - da Silveira,Juliano Coelho, AU - De Bem,Tiago Henrique Camara, AU - Perecin,Felipe, AU - Smith,Lawrence Charles, AU - Meirelles,Flávio Vieira, Y1 - 2018/09/13/ PY - 2017/10/18/received PY - 2018/05/29/accepted PY - 2018/9/15/entrez PY - 2018/9/15/pubmed PY - 2018/9/15/medline SP - 13766 EP - 13766 JF - Scientific reports JO - Sci Rep VL - 8 IS - 1 N2 - The rapid decline in fertility that has been occurring to high-producing dairy cows in the past 50 years seems to be associated with metabolic disturbances such as ketosis, supporting the need for research to improve our understanding of the relations among the diet, metabolism and embryonic development. Recently, the ketone body β-hydroxybutyrate (BOHB) was demonstrated to be a potent inhibitor of histone deacetylases (HDACs). Herein, we performed a series of experiments aiming to investigate the epigenetic effects of BOHB on histone acetylation in somatic cells, cumulus-oocyte complexes (COCs) and somatic cell nuclear transfer (SCNT) embryos. Treatment with BOHB does not increase histone acetylation in cells but stimulates genes associated with ketolysis and master regulators of metabolism. We further demonstrated that maturing COCs with high levels of BOHB does not affect their maturation rate or histone acetylation but increases the expression of PPARA in cumulus cells. Treatment of somatic cell nuclear transfer zygotes with BOHB causes hyperacetylation, which is maintained until the blastocyst stage, causing enhanced FOXO3A expression and blastocyst production. Our data shed light on the epigenetic mechanisms caused by BOHB in bovine cells and embryos and provide a better understanding of the connection between nutrition and reproduction. SN - 2045-2322 UR - https://www.unboundmedicine.com/medline/citation/30214009/Metabolic_gene_expression_and_epigenetic_effects_of_the_ketone_body_β-hydroxybutyrate_on_H3K9ac_in_bovine_cells,_oocytes_and_embryos L2 - http://dx.doi.org/10.1038/s41598-018-31822-7 DB - PRIME DP - Unbound Medicine ER -