Paternal Methyl Donor Supplementation in Rats Improves Fertility, Physiological Outcomes, Gut Microbial Signatures and Epigenetic Markers Altered by High Fat/High Sucrose Diet

Increased consumption of high fat/sucrose (HF/S) diets has contributed to rising rates of obesity and its co-morbidities globally, while also negatively impacting male reproductive health. Our objective was to examine whether adding a methyl donor cocktail to paternal HF/S diet (HF/S+M) improves hea...

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Main Authors: Faye Chleilat, Alana Schick, Julie M. Deleemans, Raylene A. Reimer
Format: Article
Language:English
Published: MDPI AG 2021-01-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/22/2/689
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author Faye Chleilat
Alana Schick
Julie M. Deleemans
Raylene A. Reimer
author_facet Faye Chleilat
Alana Schick
Julie M. Deleemans
Raylene A. Reimer
author_sort Faye Chleilat
collection DOAJ
description Increased consumption of high fat/sucrose (HF/S) diets has contributed to rising rates of obesity and its co-morbidities globally, while also negatively impacting male reproductive health. Our objective was to examine whether adding a methyl donor cocktail to paternal HF/S diet (HF/S+M) improves health status in fathers and offspring. From 3–12 weeks of age, male Sprague Dawley rats consumed a HF/S or HF/S+M diet. Offspring were followed until 16 weeks of age. Body composition, metabolic markers, gut microbiota, DNA methyltransferase (DNMT) and microRNA expression were measured in fathers and offspring. Compared to HF/S, paternal HF/S+M diet reduced fat mass in offspring (<i>p</i> < 0.005). HF/S+M fathers consumed 16% fewer kcal/day, which persisted in HF/S+M female offspring and was explained in part by changes in serum glucagon-like peptide-1 (GLP-1) and peptide tyrosine tyrosine (PYY) levels. Compared to HF/S, HF/S+M fathers had a 33% improvement in days until conception and 300% fewer stillbirths. In fathers, adipose tissue DNMT3a and hepatic miR-34a expression were reduced with HF/S+M. Adult male offspring showed upregulated miR-24, -33, -122a and -143 expression while females exhibited downregulated miR-33 expression. Fathers and offspring presented differences in gut microbial signatures. Supplementing a paternal HF/S diet with methyl-donors improved fertility, physiological outcomes, epigenetic and gut microbial signatures intergenerationally.
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spelling doaj.art-c602cf4cb8f74f869f2689d8355c79982023-12-03T12:54:19ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-01-0122268910.3390/ijms22020689Paternal Methyl Donor Supplementation in Rats Improves Fertility, Physiological Outcomes, Gut Microbial Signatures and Epigenetic Markers Altered by High Fat/High Sucrose DietFaye Chleilat0Alana Schick1Julie M. Deleemans2Raylene A. Reimer3Faculty of Kinesiology, University of Calgary, Calgary, AB T2N 1N4, CanadaInternational Microbiome Centre, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4N1, CanadaDivision of Medical Science, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4N1, CanadaFaculty of Kinesiology, University of Calgary, Calgary, AB T2N 1N4, CanadaIncreased consumption of high fat/sucrose (HF/S) diets has contributed to rising rates of obesity and its co-morbidities globally, while also negatively impacting male reproductive health. Our objective was to examine whether adding a methyl donor cocktail to paternal HF/S diet (HF/S+M) improves health status in fathers and offspring. From 3–12 weeks of age, male Sprague Dawley rats consumed a HF/S or HF/S+M diet. Offspring were followed until 16 weeks of age. Body composition, metabolic markers, gut microbiota, DNA methyltransferase (DNMT) and microRNA expression were measured in fathers and offspring. Compared to HF/S, paternal HF/S+M diet reduced fat mass in offspring (<i>p</i> < 0.005). HF/S+M fathers consumed 16% fewer kcal/day, which persisted in HF/S+M female offspring and was explained in part by changes in serum glucagon-like peptide-1 (GLP-1) and peptide tyrosine tyrosine (PYY) levels. Compared to HF/S, HF/S+M fathers had a 33% improvement in days until conception and 300% fewer stillbirths. In fathers, adipose tissue DNMT3a and hepatic miR-34a expression were reduced with HF/S+M. Adult male offspring showed upregulated miR-24, -33, -122a and -143 expression while females exhibited downregulated miR-33 expression. Fathers and offspring presented differences in gut microbial signatures. Supplementing a paternal HF/S diet with methyl-donors improved fertility, physiological outcomes, epigenetic and gut microbial signatures intergenerationally.https://www.mdpi.com/1422-0067/22/2/689paternal nutritional programmingone-carbon metabolismgut microbiotaDNMTmicroRNAinsulin resistance
spellingShingle Faye Chleilat
Alana Schick
Julie M. Deleemans
Raylene A. Reimer
Paternal Methyl Donor Supplementation in Rats Improves Fertility, Physiological Outcomes, Gut Microbial Signatures and Epigenetic Markers Altered by High Fat/High Sucrose Diet
International Journal of Molecular Sciences
paternal nutritional programming
one-carbon metabolism
gut microbiota
DNMT
microRNA
insulin resistance
title Paternal Methyl Donor Supplementation in Rats Improves Fertility, Physiological Outcomes, Gut Microbial Signatures and Epigenetic Markers Altered by High Fat/High Sucrose Diet
title_full Paternal Methyl Donor Supplementation in Rats Improves Fertility, Physiological Outcomes, Gut Microbial Signatures and Epigenetic Markers Altered by High Fat/High Sucrose Diet
title_fullStr Paternal Methyl Donor Supplementation in Rats Improves Fertility, Physiological Outcomes, Gut Microbial Signatures and Epigenetic Markers Altered by High Fat/High Sucrose Diet
title_full_unstemmed Paternal Methyl Donor Supplementation in Rats Improves Fertility, Physiological Outcomes, Gut Microbial Signatures and Epigenetic Markers Altered by High Fat/High Sucrose Diet
title_short Paternal Methyl Donor Supplementation in Rats Improves Fertility, Physiological Outcomes, Gut Microbial Signatures and Epigenetic Markers Altered by High Fat/High Sucrose Diet
title_sort paternal methyl donor supplementation in rats improves fertility physiological outcomes gut microbial signatures and epigenetic markers altered by high fat high sucrose diet
topic paternal nutritional programming
one-carbon metabolism
gut microbiota
DNMT
microRNA
insulin resistance
url https://www.mdpi.com/1422-0067/22/2/689
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