Trimethylamine N-oxide (
TMAO), a component commonly present in seafood, has been found to have a harmful impact on
glucose tolerance in high-fat diet (HFD)-fed mice. However, seafood also contains
fish oil (FO), which has been shown to have beneficial effects on metabolism. Here, we investigated the effect of FO on
TMAO-induced
impaired glucose tolerance in HFD-fed mice. Male C57BL/6 mice were randomly assigned to the high fat (HF),
TMAO, and
fish oil groups. The HF group was fed a diet containing 25% fat, the
TMAO group was fed the HFD plus 0.2%
TMAO, and the FO group was fed the HFD plus 0.2%
TMAO and 2%
fish oil for 12 weeks. After 10 weeks of feeding, oral
glucose tolerance tests were performed. Dietary FO improved the fasting
glucose level, the fasting
insulin level, HOMA-IR value, QUICKI score and ameliorated
TMAO-induced exacerbated
impaired glucose tolerance in HFD-fed mice. These effects were associated with the expression of genes related to the
insulin signalling pathway,
glycogen synthesis, gluconeogenesis, and
glucose transport in peripheral tissues. Dietary
fish oil also decreased
TMAO-aggravated adipose tissue
inflammation. Our results suggested that dietary FO ameliorated
TMAO-induced
impaired glucose tolerance,
insulin signal transduction in peripheral tissue, and adipose tissue
inflammation in HFD-fed mice.