Reference - Detail
| RRC ID | 76270 |
|---|---|
| Author | Qin S, Wang Y, Li L, Liu J, Xiao C, Duan D, Hao W, Qin C, Chen J, Yao L, Zhang R, You J, Zheng JS, Shen E, Wu L. |
| Title | Early-life vitamin B12 orchestrates lipid peroxidation to ensure reproductive success via SBP-1/SREBP1 in Caenorhabditis elegans. |
| Journal | Cell Rep |
| Abstract |
Vitamin B12 (B12) deficiency is a critical problem worldwide. Such deficiency in infants has long been known to increase the propensity to develop obesity and diabetes later in life through unclear mechanisms. Here, we establish a Caenorhabditis elegans model to study how early-life B12 impacts adult health. We find that early-life B12 deficiency causes increased lipogenesis and lipid peroxidation in adult worms, which in turn induces germline defects through ferroptosis. Mechanistically, we show the central role of the methionine cycle-SBP-1/SREBP1-lipogenesis axis in programming adult traits by early-life B12. Moreover, SBP-1/SREBP1 participates in a crucial feedback loop with NHR-114/HNF4 to maintain cellular B12 homeostasis. Inhibition of SBP-1/SREBP1-lipogenesis signaling and ferroptosis later in life can reverse disorders in adulthood when B12 cannot. Overall, this study provides mechanistic insights into the life-course effects of early-life B12 on the programming of adult health and identifies potential targets for future interventions for adiposity and infertility. |
| Volume | 40(12) |
| Pages | 111381 |
| Published | 2022-9-20 |
| DOI | 10.1016/j.celrep.2022.111381 |
| PII | S2211-1247(22)01216-5 |
| PMID | 36130518 |
| MeSH | Animals Caenorhabditis elegans* / metabolism Caenorhabditis elegans Proteins* / metabolism Lipid Peroxidation Lipogenesis Methionine Transcription Factors / metabolism Vitamin B 12 |
| Altmetric score |
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| The most frequently cited source | X(Twitter) |
| Total number of mentions | 10 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| C.elegans | tm331 |