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Transgenerational transmission of hedonic behaviors and metabolic phenotypes induced by maternal overnutrition.

Published version
Peer-reviewed

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Type

Article

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Authors

Sarker, Gitalee 
von Arx, Judith 
Pelczar, Pawel 
Reik, Wolf 

Abstract

Maternal overnutrition has been associated with increased susceptibility to develop obesity and neurological disorders later in life. Most epidemiological as well as experimental studies have focused on the metabolic consequences across generations following an early developmental nutritional insult. Recently, it has been shown that maternal high-fat diet (HFD) affects third-generation female body mass via the paternal lineage. We showed here that the offspring born to HFD ancestors displayed addictive-like behaviors as well as obesity and insulin resistance up to the third generation in the absence of any further exposure to HFD. These findings, implicate that the male germ line is a major player in transferring phenotypic traits. These behavioral and physiological alterations were paralleled by reduced striatal dopamine levels and increased dopamine 2 receptor density. Interestingly, by the third generation a clear gender segregation emerged, where females showed addictive-like behaviors while male HFD offspring showed an obesogenic phenotype. However, methylome profiling of F1 and F2 sperm revealed no significant difference between the offspring groups, suggesting that the sperm methylome might not be the major carrier for the transmission of the phenotypes observed in our mouse model. Together, our study for the first time demonstrates that maternal HFD insult causes sustained alterations of the mesolimbic dopaminergic system suggestive of a predisposition to develop obesity and addictive-like behaviors across multiple generations.

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Keywords

Animals, Behavior, Addictive, Body Weight, Diet, High-Fat, Disease Models, Animal, Female, Male, Maternal Nutritional Physiological Phenomena, Metabolic Syndrome, Mice, Mice, Inbred C57BL, Obesity, Overnutrition, Pregnancy, Prenatal Exposure Delayed Effects

Journal Title

Transl Psychiatry

Conference Name

Journal ISSN

2158-3188
2158-3188

Volume Title

8

Publisher

Springer Science and Business Media LLC