Circadian Rhythm\nEnhances mTORC1/AMPK Pathway-Mediated\nMilk Fat Synthesis in Dairy Cows via the Microbial Metabolite Acetic\nAcid

Livestock\nmay respond differently to circadian rhythms,\nleading\nto differences in the composition of the animal products. Nevertheless,\nthe circadian effects on rumen microorganisms and animal products\nare poorly understood. In the study, it was found that dairy cows\nexhibited increased milk fat levels, decreased acetic acid concentrations\nin the rumen fluid, and elevated acetic acid levels in the blood during\nthe night compared to those of the day. Correlational analyses suggested\na high association between <i>Succiniclasticum</i>, <i>Lactobacillus</i>, <i>Prevotellacene NK3B31_group</i>, <i>Muribaculaceae_unclassified</i>, etc., which were\nsignificantly enriched in rumen fluid at night, and milk fat levels.\nThe differential metabolite Vitamin B6, significantly elevated at\nnight, promoted the translocation of acetic acid into the circulation\nby increasing the level of rumen epithelial MCT1 protein expression.\nIn addition, we found that both acetic acid treatment time and dose\nmodulated the expression of lipid metabolism transcription factors\n(PPARγ, PPARα, and SREBP1c) and downstream genes (FASN,\nSCD1, ACCα, and CPT1A). Additionally, the mTORC1 and AMPK pathways\nwere responsible for the effects of acetic acid on transcription factors\nand genes involved in lipid metabolism. Differences in rumen microbial\ntaxa were observed between the day and night. Microbial metabolite\n(acetic acid) was found to be absorbed into the bloodstream and entered\nthe mammary gland at night at a significantly elevated level. This\nregulation impacted the expression of lipid metabolism-related transcription\nfactors (PPARγ, PPARα, and SREBP1c), as well as downstream\ngenes through the mTORC1 and AMPK signaling pathways, ultimately affecting\nmilk fat synthesis. These findings provide a new perspective for the\nmicrobial regulation of milk synthesis.