論文 - 詳細
| RRC ID | 76202 |
|---|---|
| 著者 | Jordan JM, Webster AK, Chen J, Chitrakar R, Ryan Baugh L. |
| タイトル | Early-life starvation alters lipid metabolism in adults to cause developmental pathology in Caenorhabditis elegans. |
| ジャーナル | Genetics |
| Abstract |
Early-life malnutrition increases adult disease risk in humans, but the causal changes in gene regulation, signaling, and metabolism are unclear. In the roundworm Caenorhabditis elegans, early-life starvation causes well-fed larvae to develop germline tumors and other gonad abnormalities as adults. Furthermore, reduced insulin/IGF signaling during larval development suppresses these starvation-induced abnormalities. How early-life starvation and insulin/IGF signaling affect adult pathology is unknown. We show that early-life starvation has pervasive effects on adult gene expression which are largely reversed by reduced insulin/IGF signaling following recovery from starvation. Early-life starvation increases adult fatty-acid synthetase fasn-1 expression in daf-2 insulin/IGF signaling receptor-dependent fashion, and fasn-1/FASN promotes starvation-induced abnormalities. Lipidomic analysis reveals increased levels of phosphatidylcholine in adults subjected to early-life starvation, and supplementation with unsaturated phosphatidylcholine during development suppresses starvation-induced abnormalities. Genetic analysis of fatty-acid desaturases reveals positive and negative effects of desaturation on development of starvation-induced abnormalities. In particular, the ω3 fatty-acid desaturase fat-1 and the Δ5 fatty-acid desaturase fat-4 inhibit and promote development of abnormalities, respectively. fat-4 is epistatic to fat-1, suggesting that arachidonic acid-containing lipids promote development of starvation-induced abnormalities, and supplementation with ARA enhanced development of abnormalities. This work shows that early-life starvation and insulin/IGF signaling converge on regulation of adult lipid metabolism, affecting stem-cell proliferation and tumor formation. |
| 巻・号 | 223(2) |
| 公開日 | 2023-2-9 |
| DOI | 10.1093/genetics/iyac172 |
| PII | 6855282 |
| PMID | 36449523 |
| PMC | PMC9910403 |
| MeSH | Animals Caenorhabditis elegans / metabolism Caenorhabditis elegans Proteins* / genetics Caenorhabditis elegans Proteins* / metabolism Humans Insulin / metabolism Lipid Metabolism Starvation* / genetics |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 7 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.2 |
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