Abstract
As a major risk factor to human health, obesity presents a massive burden to people and society. Interestingly, the obese status of parents can cause progeny’s lipid accumulation through epigenetic inheritance in multiple species. To date, many questions remain as to how lipid accumulation leads to signals that are transmitted across generations. In this study, we establish a nematode model of C. elegans raised on a high-fat diet (HFD) that leads to measurable lipid accumulation, which can transmit the lipid accumulation signal to their multigenerational progeny. Using this model, we find that transcription factors DAF-16/FOXO and SBP-1/SREBP, nuclear receptors NHR-49 and NHR-80, and delta-9 desaturases (fat-5, fat-6, and fat-7) are required for transgenerational lipid accumulation. Additionally, histone H3K4 trimethylation (H3K4me3) marks lipid metabolism genes and increases their transcription response to multigenerational obesogenic effects. In summary, this study establishes an interaction between a network of lipid metabolic genes and chromatin modifications, which work together to achieve transgenerational epigenetic inheritance of obesogenic effects.
Highlights
As a major risk factor to human health, obesity presents a massive burden to people and society
Using OilRed-O (ORO) staining, we found that the ORO level was obviously elevated when animals were fed with oleic acid (OA), palmitoleic acid (PA), cholesterol, or egg yolk compared with the OP50 medium, and that supplementation with egg yolk showed the most significant lipid accumulation (Fig. 1a)
We found that the ORO levels were significantly increased, in both high-fat diet (HFD)-fed parents and their F1 and F2 progeny recovered on normal OP50 (Fig. 1c, d), suggesting that HFD can induce a multigenerational epigenetic inheritance phenotype on descendants from a single exposure of the P0 generation
Summary
As a major risk factor to human health, obesity presents a massive burden to people and society. We establish a nematode model of C. elegans raised on a high-fat diet (HFD) that leads to measurable lipid accumulation, which can transmit the lipid accumulation signal to their multigenerational progeny. Using this model, we find that transcription factors DAF-16/ FOXO and SBP-1/SREBP, nuclear receptors NHR-49 and NHR-80, and delta-9 desaturases (fat-5, fat-6, and fat-7) are required for transgenerational lipid accumulation. It was reported that the TEI obesogenic effects of sulfomethoxazole are associated with histone H3K4me[3] modification[19]; another study indicated that a reduction in lipid accumulation induced by benzylisoquinoline can be transmitted to progeny[20]. We characterize the critical factors functioning for “implementation” or “transmission” in TEI of lipid accumulation in C. elegans
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