Early-life vitamin B12 orchestrates lipid peroxidation to ensure reproductive success via SBP-1/SREBP1 in Caenorhabditis elegans

Cell Rep. 2022 Sep 20;40(12):111381. doi: 10.1016/j.celrep.2022.111381.


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.

Keywords: CP: Developmental biology; CP: Metabolism; DOHaD; SREBP1; adiposity; adulthood disorder; developmental programming; early life; ferroptosis; infertility; lipogenesis; vitamin B12.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Caenorhabditis elegans Proteins* / metabolism
  • Caenorhabditis elegans* / metabolism
  • Lipid Peroxidation
  • Lipogenesis
  • Methionine
  • Transcription Factors / metabolism
  • Vitamin B 12


  • Caenorhabditis elegans Proteins
  • SBP-1 protein, C elegans
  • Transcription Factors
  • Methionine
  • Vitamin B 12