Elsevier

Molecular Metabolism

Volume 6, Issue 7, July 2017, Pages 631-639
Molecular Metabolism

Original Article
Parental obesity leads to metabolic changes in the F2 generation in Drosophila

https://doi.org/10.1016/j.molmet.2017.03.012Get rights and content
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Highlights

  • Haploinsufficiency for AKHR affects metabolite levels and gene expression.

  • Genetic alteration of parental metabolism leads to heritable effects on offspring

  • Parental obesity selectively affects the grandpaternal/maternal lineage.

Abstract

Objective

A significant portion of the heritable risk for complex metabolic disorders cannot be attributed to classic Mendelian genetic factors. At least some of this missing heritability is thought to be due to the epigenetic influence of parental and grandparental metabolic state on offspring health. Previous work suggests that this transgenerational phenomenon is evolutionarily conserved in Drosophila. These studies, however, have all depended on dietary paradigms to alter parental metabolic state, which can have inconsistent heritable effects on the metabolism of offspring.

Methods

Here we use AKHR null alleles to induce obesity in the parental generation and then score both metabolic parameters and genome-wide transcriptional responses in AKHR heterozygote F1 progeny and genetically wild-type F2 progeny.

Results

Unexpectedly, we observe elevated glycogen levels and changes in gene expression in AKHR heterozygotes due to haploinsufficiency at this locus. We also show that genetic manipulation of parental metabolism using AKHR mutations results in significant physiological changes in F2 wild-type offspring of the grandpaternal/maternal lineage.

Conclusions

Our results demonstrate that genetic manipulation of parental metabolism in Drosophila can have an effect on the health of F2 progeny, providing a non-dietary paradigm to better understand the mechanisms behind the transgenerational inheritance of metabolic state.

Keywords

Physiology
Transgenerational inheritance
Obesity
Drosophila metabolism

Abbreviations

AKH
Adipokinetic hormone
AKHR
Adipokinetic Hormone Receptor
GO
Gene Ontology
bmm
brummer

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