Cold-induced epigenetic programming of the sperm enhances brown adipose tissue activity in the offspring

Wenfei Sun; Hua Dong; Anton S Becker; Dianne H Dapito; Salvatore Modica; Gerald Grandl; Lennart Opitz; Vissarion Efthymiou; Leon G Straub; Gitalee Sarker; Miroslav Balaz; Lucia Balazova; Aliki Perdikari; Elke Kiehlmann; Sara Bacanovic; Caroline Zellweger; Daria Peleg-Raibstein; Pawel Pelczar; Wolf Reik; Irene A Burger; Ferdinand von Meyenn; Christian Wolfrum

doi:10.1038/s41591-018-0102-y

Cold-induced epigenetic programming of the sperm enhances brown adipose tissue activity in the offspring

Wenfei Sun, Hua Dong, Anton S Becker, Dianne H Dapito, Salvatore Modica, Gerald Grandl, Lennart Opitz, Vissarion Efthymiou, Leon G Straub, Gitalee Sarker, Miroslav Balaz, Lucia Balazova, Aliki Perdikari, Elke Kiehlmann, Sara Bacanovic, Caroline Zellweger, Daria Peleg-Raibstein, Pawel Pelczar, Wolf Reik, Irene A BurgerFerdinand von Meyenn, Christian Wolfrum

Medical & Molecular Genetics

Research output: Contribution to journal › Article › peer-review

82 Citations (Scopus)

833 Downloads (Pure)

Abstract

Recent research has focused on environmental effects that control tissue functionality and systemic metabolism. However, whether such stimuli affect human thermogenesis and body mass index (BMI) has not been explored. Here we show retrospectively that the presence of brown adipose tissue (BAT) and the season of conception are linked to BMI in humans. In mice, we demonstrate that cold exposure (CE) of males, but not females, before mating results in improved systemic metabolism and protection from diet-induced obesity of the male offspring. Integrated analyses of the DNA methylome and RNA sequencing of the sperm from male mice revealed several clusters of co-regulated differentially methylated regions (DMRs) and differentially expressed genes (DEGs), suggesting that the improved metabolic health of the offspring was due to enhanced BAT formation and increased neurogenesis. The conclusions are supported by cell-autonomous studies in the offspring that demonstrate an enhanced capacity to form mature active brown adipocytes, improved neuronal density and more norepinephrine release in BAT in response to cold stimulation. Taken together, our results indicate that in humans and in mice, seasonal or experimental CE induces an epigenetic programming of the sperm such that the offspring harbor hyperactive BAT and an improved adaptation to overnutrition and hypothermia.

Original language	English
Journal	Nature Medicine
Early online date	9 Jul 2018
DOIs	https://doi.org/10.1038/s41591-018-0102-y
Publication status	E-pub ahead of print - 9 Jul 2018

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1038/s41591-018-0102-y

Cold-induced epigenetic programming_SUN_Accepted21May2018_GREEN AAMAccepted author manuscript, 3.85 MB

Cite this

Sun, W., Dong, H., Becker, A. S., Dapito, D. H., Modica, S., Grandl, G., Opitz, L., Efthymiou, V., Straub, L. G., Sarker, G., Balaz, M., Balazova, L., Perdikari, A., Kiehlmann, E., Bacanovic, S., Zellweger, C., Peleg-Raibstein, D., Pelczar, P., Reik, W., ... Wolfrum, C. (2018). Cold-induced epigenetic programming of the sperm enhances brown adipose tissue activity in the offspring. Nature Medicine. Advance online publication. https://doi.org/10.1038/s41591-018-0102-y

@article{d206169d85d44932b49655e7c842ed9b,

title = "Cold-induced epigenetic programming of the sperm enhances brown adipose tissue activity in the offspring",

abstract = "Recent research has focused on environmental effects that control tissue functionality and systemic metabolism. However, whether such stimuli affect human thermogenesis and body mass index (BMI) has not been explored. Here we show retrospectively that the presence of brown adipose tissue (BAT) and the season of conception are linked to BMI in humans. In mice, we demonstrate that cold exposure (CE) of males, but not females, before mating results in improved systemic metabolism and protection from diet-induced obesity of the male offspring. Integrated analyses of the DNA methylome and RNA sequencing of the sperm from male mice revealed several clusters of co-regulated differentially methylated regions (DMRs) and differentially expressed genes (DEGs), suggesting that the improved metabolic health of the offspring was due to enhanced BAT formation and increased neurogenesis. The conclusions are supported by cell-autonomous studies in the offspring that demonstrate an enhanced capacity to form mature active brown adipocytes, improved neuronal density and more norepinephrine release in BAT in response to cold stimulation. Taken together, our results indicate that in humans and in mice, seasonal or experimental CE induces an epigenetic programming of the sperm such that the offspring harbor hyperactive BAT and an improved adaptation to overnutrition and hypothermia.",

author = "Wenfei Sun and Hua Dong and Becker, {Anton S} and Dapito, {Dianne H} and Salvatore Modica and Gerald Grandl and Lennart Opitz and Vissarion Efthymiou and Straub, {Leon G} and Gitalee Sarker and Miroslav Balaz and Lucia Balazova and Aliki Perdikari and Elke Kiehlmann and Sara Bacanovic and Caroline Zellweger and Daria Peleg-Raibstein and Pawel Pelczar and Wolf Reik and Burger, {Irene A} and {von Meyenn}, Ferdinand and Christian Wolfrum",

year = "2018",

month = jul,

day = "9",

doi = "10.1038/s41591-018-0102-y",

language = "English",

journal = "Nature Medicine",

issn = "1078-8956",

publisher = "Nature Publishing Group",

}

Sun, W, Dong, H, Becker, AS, Dapito, DH, Modica, S, Grandl, G, Opitz, L, Efthymiou, V, Straub, LG, Sarker, G, Balaz, M, Balazova, L, Perdikari, A, Kiehlmann, E, Bacanovic, S, Zellweger, C, Peleg-Raibstein, D, Pelczar, P, Reik, W, Burger, IA, von Meyenn, F & Wolfrum, C 2018, 'Cold-induced epigenetic programming of the sperm enhances brown adipose tissue activity in the offspring', Nature Medicine. https://doi.org/10.1038/s41591-018-0102-y

TY - JOUR

T1 - Cold-induced epigenetic programming of the sperm enhances brown adipose tissue activity in the offspring

AU - Sun, Wenfei

AU - Dong, Hua

AU - Becker, Anton S

AU - Dapito, Dianne H

AU - Modica, Salvatore

AU - Grandl, Gerald

AU - Opitz, Lennart

AU - Efthymiou, Vissarion

AU - Straub, Leon G

AU - Sarker, Gitalee

AU - Balaz, Miroslav

AU - Balazova, Lucia

AU - Perdikari, Aliki

AU - Kiehlmann, Elke

AU - Bacanovic, Sara

AU - Zellweger, Caroline

AU - Peleg-Raibstein, Daria

AU - Pelczar, Pawel

AU - Reik, Wolf

AU - Burger, Irene A

AU - von Meyenn, Ferdinand

AU - Wolfrum, Christian

PY - 2018/7/9

Y1 - 2018/7/9

N2 - Recent research has focused on environmental effects that control tissue functionality and systemic metabolism. However, whether such stimuli affect human thermogenesis and body mass index (BMI) has not been explored. Here we show retrospectively that the presence of brown adipose tissue (BAT) and the season of conception are linked to BMI in humans. In mice, we demonstrate that cold exposure (CE) of males, but not females, before mating results in improved systemic metabolism and protection from diet-induced obesity of the male offspring. Integrated analyses of the DNA methylome and RNA sequencing of the sperm from male mice revealed several clusters of co-regulated differentially methylated regions (DMRs) and differentially expressed genes (DEGs), suggesting that the improved metabolic health of the offspring was due to enhanced BAT formation and increased neurogenesis. The conclusions are supported by cell-autonomous studies in the offspring that demonstrate an enhanced capacity to form mature active brown adipocytes, improved neuronal density and more norepinephrine release in BAT in response to cold stimulation. Taken together, our results indicate that in humans and in mice, seasonal or experimental CE induces an epigenetic programming of the sperm such that the offspring harbor hyperactive BAT and an improved adaptation to overnutrition and hypothermia.

AB - Recent research has focused on environmental effects that control tissue functionality and systemic metabolism. However, whether such stimuli affect human thermogenesis and body mass index (BMI) has not been explored. Here we show retrospectively that the presence of brown adipose tissue (BAT) and the season of conception are linked to BMI in humans. In mice, we demonstrate that cold exposure (CE) of males, but not females, before mating results in improved systemic metabolism and protection from diet-induced obesity of the male offspring. Integrated analyses of the DNA methylome and RNA sequencing of the sperm from male mice revealed several clusters of co-regulated differentially methylated regions (DMRs) and differentially expressed genes (DEGs), suggesting that the improved metabolic health of the offspring was due to enhanced BAT formation and increased neurogenesis. The conclusions are supported by cell-autonomous studies in the offspring that demonstrate an enhanced capacity to form mature active brown adipocytes, improved neuronal density and more norepinephrine release in BAT in response to cold stimulation. Taken together, our results indicate that in humans and in mice, seasonal or experimental CE induces an epigenetic programming of the sperm such that the offspring harbor hyperactive BAT and an improved adaptation to overnutrition and hypothermia.

U2 - 10.1038/s41591-018-0102-y

DO - 10.1038/s41591-018-0102-y

M3 - Article

C2 - 29988127

SN - 1078-8956

JO - Nature Medicine

JF - Nature Medicine

ER -

Cold-induced epigenetic programming of the sperm enhances brown adipose tissue activity in the offspring

Abstract

UN SDGs

Access to Document

Fingerprint

Cite this