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Parental obesity leads to metabolic changes in the F2 generation in Drosophila
- Source :
- Molecular Metabolism, Vol 6, Iss 7, Pp 631-639 (2017)
- Publication Year :
- 2017
- Publisher :
- Elsevier, 2017.
-
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.
- Subjects :
- 2. Zero hunger
0301 basic medicine
Genetics
lcsh:Internal medicine
Drosophila metabolism
Offspring
Physiology
Heterozygote advantage
Cell Biology
Biology
Null allele
03 medical and health sciences
symbols.namesake
030104 developmental biology
Missing heritability problem
Mendelian inheritance
symbols
Epigenetics
Obesity
Genomic imprinting
Haploinsufficiency
lcsh:RC31-1245
Molecular Biology
Transgenerational inheritance
Subjects
Details
- Language :
- English
- ISSN :
- 22128778
- Volume :
- 6
- Issue :
- 7
- Database :
- OpenAIRE
- Journal :
- Molecular Metabolism
- Accession number :
- edsair.doi.dedup.....3685183ed4cf3ba97c6b81bdc2a08712