Short-term and long-term high-fat diet promote metabolic disorder through reprogramming mRNA m⁶A in white adipose tissue by gut microbiota.

ABSTRACT:

Background

Although short-term high-fat diet (S-HFD) and long-term high-fat diet (L-HFD) induce metabolic disorder, the underlying epigenetic mechanism is still unclear.

Results

Here, we found that both 4 days of S-HFD and 10 weeks of L-HFD increased mRNA m⁶A level in epididymal white adipose tissue (eWAT) and impaired metabolic health. Interestingly, S-HFD activated transposable elements (TEs), especially endogenous retroviruses (ERVs) in eWAT, while L-HFD activated long interspersed elements (LINEs). Subsequently, we demonstrated that both S-HFD and L-HFD increased m⁶A level of Ehmt2 and decreased EHMT2 protein expression and H3K9me2 level, accounting for activation of ERVs and LINEs. Overexpression of EHMT2 in eWAT or inhibition of ERVs and LINEs by

SUBMITTER: Liu Y 

PROVIDER: S-EPMC11912683 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature