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Maternal Metabolic Syndrome Programs Mitochondrial Dysfunction via Germline Changes across Three Generations

Maternal obesity impairs offspring health, but the responsible mechanisms are not fully established. To address this question, we fed female mice a high-fat/high-sugar diet from before conception until weaning and then followed the outcomes in the next three generations of offspring, all fed a contr...

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Bibliographic Details
Published in:Cell reports (Cambridge) 2016-06, Vol.16 (1), p.1-8
Main Authors: Saben, Jessica L., Boudoures, Anna L., Asghar, Zeenat, Thompson, Alysha, Drury, Andrea, Zhang, Wendy, Chi, Maggie, Cusumano, Andrew, Scheaffer, Suzanne, Moley, Kelle H.
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Language:English
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Summary:Maternal obesity impairs offspring health, but the responsible mechanisms are not fully established. To address this question, we fed female mice a high-fat/high-sugar diet from before conception until weaning and then followed the outcomes in the next three generations of offspring, all fed a control diet. We observed that female offspring born to obese mothers had impaired peripheral insulin signaling that was associated with mitochondrial dysfunction and altered mitochondrial dynamic and complex proteins in skeletal muscle. This mitochondrial phenotype persisted through the female germline and was passed down to the second and third generations. Our results indicate that maternal programming of metabolic disease can be passed through the female germline and that the transfer of aberrant oocyte mitochondria to subsequent generations may contribute to the increased risk for developing insulin resistance. [Display omitted] •Inbred mice fed a high-fat/high-sucrose (HF/HS) diet develop metabolic syndrome•F1, F2, and F3 offspring from HF/HS-fed dams develop mitochondrial dysfunction•Proteins involved in mitochondrial dynamics and ETC are misexpressed in F1–F3 pups•Mitochondrial changes are seen in F1–F2 oocytes, suggesting germline transmission Saben et al. demonstrate that maternal diet-induced metabolic syndrome in an inbred mouse model results in transgenerational inheritance of aberrant mitochondria. Abnormal expression of mitochondrial ETC complex and dynamic proteins are seen in F1–F3, despite the fact that they are eating a regular diet. The transmission appears to be germline and through aberrant oocytes.
ISSN:2211-1247
2211-1247
DOI:10.1016/j.celrep.2016.05.065