Paternal multigenerational exposure to an obesogenic diet drives epigenetic predisposition to metabolic diseases in mice

eLife

Didier F Pisani¹  Ez-Zoubir Amri¹  Luc Martin¹  Marie-Alix Derieppe¹  Jérôme Gilleron²  Valerie Grandjean³  Fabrizio Serra³  Vera L Costa³  Michele Trabucchi³  Georges Raad⁴ 

[1] Université Côte d'Azur, CNRS, Inserm, iBV, Nice, France;Université Côte d’Azur, Inserm, C3M, Team Cellular and Molecular Pathophysiology of Obesity and Diabetes (7), Nice, France;Université Côte d’Azur, Inserm, C3M, TeamControl of Gene Expression (10), Nice, France;Université Côte d’Azur, Inserm, C3M, TeamControl of Gene Expression (10), Nice, France;Université Côte d'Azur, CNRS, Inserm, iBV, Nice, France;

关键词: epigenetic;    inheritance;    sperm;    obesity;    Mouse;   

DOI  :  10.7554/eLife.61736

来源: eLife Sciences Publications, Ltd

【 摘 要 】

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 four 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.

【 授权许可】

CC BY