AMPK inhibition and elevated angiogenin are associated with tRNA fragmentation in the male germline exposed to a high-fat diet

To explore a mechanism underlying metabolic stress-induced tRNA fragmentation, we examined the effects of a HFD on tRFs in sperm.

Small RNA sequencing on sperm revealed that HFD-induced metabolic changes affect the tRF profiles, showing a trend of decreased 5’-derived tRFs and increased 3’-derived tRFs, suggesting a shift in tRNA cleavage patterns under HFD feeding. In conjunction with the alteration of tRFs, the expression of Ang, which encodes the ribonuclease angiogenin, was significantly increased in the testis. Transcriptome and metabolome analyses indicated that AMPK-mTOR signaling pathway was the possible mediator of these effects, with decreased AMPK activity and increased mTOR activity confirmed at the protein level in the testis.