Paternal multigenerational exposure to an obesogenic diet drives epigenetic predisposition to metabolic diseases in mice
- Université Côte d'Azur, CNRS, Inserm, France
- Inserm, France
- French Institute of Health and Medical Research, France
Abstract
Obesity is a growing societal scourge. Recent studies have uncovered that paternal excessive weight induced by an unbalanced diet affects the metabolic health of offspring. These reports mainly employed single-generation male exposure. However, the consequences of multigenerational unbalanced diet feeding on the metabolic health of progeny remain largely unknown. Here, we show that maintaining paternal western diet feeding for five consecutive generations in mice induces an enhancement in fat mass and related metabolic diseases over generations. Strikingly, chow-diet-fed progenies from these multigenerational western-diet-fed males develop a 'healthy' overweight phenotype characterized by normal glucose metabolism and without fatty liver that persists for 4 subsequent generations. Mechanistically, sperm RNA microinjection experiments into zygotes suggest that sperm RNAs are sufficient for establishment but not for long-term maintenance of epigenetic inheritance of metabolic pathologies. Progressive and permanent metabolic deregulation induced by successive paternal western-diet-fed generations may contribute to the worldwide epidemic of metabolic diseases.
Data availability
Sequencing data have been deposited in GEO under accession codes GSE138989 and GSE148972. All data generated or analyses during this study are included in the manuscript and supporting files.
Article and author information
Author details
Funding
Agence Nationale de la Recherche (NR-12-ADAPT-0022)
- Georges Raad
Fonds Francais pour l'Alimentation et la Sante (15D52)
- Marie-Alix Derieppe
UCA-IDEX
- Fabrizio Serra
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: All mouse experiments were conducted in accordance with the French and European legislations for the care and use of research animals. All of the animals were handled according to approved institutional animal care and use committee (APAFIS#8729-2017012716401597 (V7)) protocols (#381) of the Ministère de l'Enseignement Supérieur de la Recherche et de l'innovation. The protocol was approved by the Committee on the Ethics of Animal Experiments of the University of Nice (Permit Number: 217-36).
Copyright
© 2021, Raad et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Paternal multigenerational exposure to an obesogenic diet drives epigenetic predisposition to metabolic diseases in mice
eLife 10:e61736.
https://doi.org/10.7554/eLife.61736
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