Dietary trimethylamine N-oxide exacerbates impaired glucose tolerance in mice fed a high fat diet

J Biosci Bioeng. 2014 Oct;118(4):476-81. doi: 10.1016/j.jbiosc.2014.03.001. Epub 2014 Apr 8.


Trimethylamine N-oxide (TMAO) is an oxidation product of trimethylamine (TMA) and is present in many aquatic foods. Here, we investigated the effects of TMAO on glucose tolerance in high fat diet (HFD)-fed mice. Male C57BL/6 mice were randomly assigned to the control, high fat (HF), and TMAO groups. The HF group was fed a diet containing 25% fat, and the TMAO group was fed the HFD plus 0.2% TMAO for 4 weeks. After 3 weeks of feeding, oral glucose tolerance tests were performed. Dietary TMAO increased fasting insulin levels and homeostasis model assessment-estimated insulin resistance (HOMA-IR) and exacerbated the impaired glucose tolerance in HFD-fed mice. These effects were associated with the expression of genes related to the insulin signal pathway, glycogen synthesis, gluconeogenesis and glucose transport in liver. mRNA levels of the pro-inflammatory cytokine MCP-1 increased significantly and of the anti-inflammatory cytokine IL-10 greatly decreased in adipose tissue. Our results suggest that dietary TMAO exacerbates impaired glucose tolerance, obstructs the hepatic insulin signaling pathway, and causes adipose tissue inflammation in mice fed a high fat diet.

Keywords: Glucose tolerance; High fat diet; Inflammation; Insulin resistance; Trimethylamine N-oxide.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue / drug effects
  • Adipose Tissue / metabolism
  • Adipose Tissue / pathology
  • Animals
  • Blood Glucose / metabolism
  • Chemokine CCL2 / metabolism
  • Diet, High-Fat*
  • Dietary Fats / adverse effects*
  • Fasting
  • Glucose Intolerance / etiology*
  • Glucose Intolerance / metabolism
  • Glucose Tolerance Test
  • Inflammation
  • Insulin / blood
  • Insulin Resistance
  • Interleukin-10 / metabolism
  • Liver / drug effects
  • Liver / metabolism
  • Male
  • Methylamines / adverse effects*
  • Mice
  • Mice, Inbred C57BL


  • Blood Glucose
  • Ccl2 protein, mouse
  • Chemokine CCL2
  • Dietary Fats
  • IL10 protein, mouse
  • Insulin
  • Methylamines
  • Interleukin-10
  • trimethyloxamine