Obesity and Bariatric Surgery Drive Epigenetic Variation of Spermatozoa in Humans

Ida Donkin; Soetkin Versteyhe; Lars R Ingerslev; Kui Qian; Mie Mechta; Loa Nordkap; Brynjulf Mortensen; Emil Vincent R Appel; Niels Jørgensen; Viggo B Kristiansen; Torben Hansen; Christopher T. Workman; Juleen R Zierath; Romain Barrès

doi:10.1016/j.cmet.2015.11.004

Obesity and Bariatric Surgery Drive Epigenetic Variation of Spermatozoa in Humans

Ida Donkin, Soetkin Versteyhe, Lars R Ingerslev, Kui Qian, Mie Mechta, Loa Nordkap, Brynjulf Mortensen, Emil Vincent R Appel, Niels Jørgensen, Viggo B Kristiansen, Torben Hansen, Christopher T. Workman, Juleen R Zierath, Romain Barrès

Institut for Klinisk Medicin

254 Citationer (Scopus)

Abstract

Obesity is a heritable disorder, with children of obese fathers at higher risk of developing obesity. Environmental factors epigenetically influence somatic tissues, but the contribution of these factors to the establishment of epigenetic patterns in human gametes is unknown. Here, we hypothesized that weight loss remodels the epigenetic signature of spermatozoa in human obesity. Comprehensive profiling of the epigenome of sperm from lean and obese men showed similar histone positioning, but small non-coding RNA expression and DNA methylation patterns were markedly different. In a separate cohort of morbidly obese men, surgery-induced weight loss was associated with a dramatic remodeling of sperm DNA methylation, notably at genetic locations implicated in the central control of appetite. Our data provide evidence that the epigenome of human spermatozoa dynamically changes under environmental pressure and offers insight into how obesity may propagate metabolic dysfunction to the next generation.

Originalsprog	Engelsk
Tidsskrift	Cell Metabolism
Vol/bind	23
Udgave nummer	2
Sider (fra-til)	369-78
Antal sider	10
ISSN	1550-4131
DOI	https://doi.org/10.1016/j.cmet.2015.11.004
Status	Udgivet - 9 feb. 2016

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10.1016/j.cmet.2015.11.004

http://www.cell.com/article/S1550413115005719/pdf

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Donkin, I., Versteyhe, S., Ingerslev, L. R., Qian, K., Mechta, M., Nordkap, L., Mortensen, B., Appel, E. V. R., Jørgensen, N., Kristiansen, V. B., Hansen, T., Workman, C. T., Zierath, J. R., & Barrès, R. (2016). Obesity and Bariatric Surgery Drive Epigenetic Variation of Spermatozoa in Humans. Cell Metabolism, 23(2), 369-78. https://doi.org/10.1016/j.cmet.2015.11.004

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title = "Obesity and Bariatric Surgery Drive Epigenetic Variation of Spermatozoa in Humans",

abstract = "Obesity is a heritable disorder, with children of obese fathers at higher risk of developing obesity. Environmental factors epigenetically influence somatic tissues, but the contribution of these factors to the establishment of epigenetic patterns in human gametes is unknown. Here, we hypothesized that weight loss remodels the epigenetic signature of spermatozoa in human obesity. Comprehensive profiling of the epigenome of sperm from lean and obese men showed similar histone positioning, but small non-coding RNA expression and DNA methylation patterns were markedly different. In a separate cohort of morbidly obese men, surgery-induced weight loss was associated with a dramatic remodeling of sperm DNA methylation, notably at genetic locations implicated in the central control of appetite. Our data provide evidence that the epigenome of human spermatozoa dynamically changes under environmental pressure and offers insight into how obesity may propagate metabolic dysfunction to the next generation.",

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doi = "10.1016/j.cmet.2015.11.004",

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T1 - Obesity and Bariatric Surgery Drive Epigenetic Variation of Spermatozoa in Humans

AU - Donkin, Ida

AU - Versteyhe, Soetkin

AU - Ingerslev, Lars R

AU - Qian, Kui

AU - Mechta, Mie

AU - Nordkap, Loa

AU - Mortensen, Brynjulf

AU - Appel, Emil Vincent R

AU - Jørgensen, Niels

AU - Kristiansen, Viggo B

AU - Hansen, Torben

AU - Workman, Christopher T.

AU - Zierath, Juleen R

AU - Barrès, Romain

PY - 2016/2/9

Y1 - 2016/2/9

N2 - Obesity is a heritable disorder, with children of obese fathers at higher risk of developing obesity. Environmental factors epigenetically influence somatic tissues, but the contribution of these factors to the establishment of epigenetic patterns in human gametes is unknown. Here, we hypothesized that weight loss remodels the epigenetic signature of spermatozoa in human obesity. Comprehensive profiling of the epigenome of sperm from lean and obese men showed similar histone positioning, but small non-coding RNA expression and DNA methylation patterns were markedly different. In a separate cohort of morbidly obese men, surgery-induced weight loss was associated with a dramatic remodeling of sperm DNA methylation, notably at genetic locations implicated in the central control of appetite. Our data provide evidence that the epigenome of human spermatozoa dynamically changes under environmental pressure and offers insight into how obesity may propagate metabolic dysfunction to the next generation.

AB - Obesity is a heritable disorder, with children of obese fathers at higher risk of developing obesity. Environmental factors epigenetically influence somatic tissues, but the contribution of these factors to the establishment of epigenetic patterns in human gametes is unknown. Here, we hypothesized that weight loss remodels the epigenetic signature of spermatozoa in human obesity. Comprehensive profiling of the epigenome of sperm from lean and obese men showed similar histone positioning, but small non-coding RNA expression and DNA methylation patterns were markedly different. In a separate cohort of morbidly obese men, surgery-induced weight loss was associated with a dramatic remodeling of sperm DNA methylation, notably at genetic locations implicated in the central control of appetite. Our data provide evidence that the epigenome of human spermatozoa dynamically changes under environmental pressure and offers insight into how obesity may propagate metabolic dysfunction to the next generation.

U2 - 10.1016/j.cmet.2015.11.004

DO - 10.1016/j.cmet.2015.11.004

M3 - Journal article

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SP - 369

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JO - Cell Metabolism

JF - Cell Metabolism

IS - 2

ER -

Obesity and Bariatric Surgery Drive Epigenetic Variation of Spermatozoa in Humans

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