Early-life vitamin B12 orchestrates lipid peroxidation to ensure reproductive success via SBP-1/SREBP1 in Caenorhabditis elegans
0301 basic medicine
Vitamin B 12
03 medical and health sciences
Methionine
Lipogenesis
Animals
Lipid Peroxidation
Caenorhabditis elegans
Caenorhabditis elegans Proteins
Transcription Factors
DOI:
10.1016/j.celrep.2022.111381
Publication Date:
2022-09-20T14:51:18Z
AUTHORS (15)
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.
SUPPLEMENTAL MATERIAL
Coming soon ....
REFERENCES (65)
CITATIONS (33)
EXTERNAL LINKS
PlumX Metrics
RECOMMENDATIONS
FAIR ASSESSMENT
Coming soon ....
JUPYTER LAB
Coming soon ....