Dietary trimethylamine N-oxide exacerbates impaired glucose tolerance in mice fed a high fat diet
Abstract
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.
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In high-fat-fed C57Bl/6 mice, TMAO feeding increased diet-induced glucose intolerance, as measured by higher fasting insulin and HOMA-IR, along with altered insulin signaling and increased inflammatory markers.
“In high-fat-fed C57Bl/6 mice, TMAO feeding increases the glucose intolerance induced by the diet as measured by higher fasting insulin levels and the homeostasis model assessment (HOMA) for insulin resistance scores along with altered insulin signaling and increased inflammatory markers (44).”
From Trimethylamine <i>N</i> -Oxide, the Microbiome, and Heart and Kidney Disease (2017) · cites this paper as [44]
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- Authors
- Gao, X., Liu, X., Xu, J., Xue, C., Xue, Y., & Wang, Y.
- Affiliations
- Ocean University of China (CN)
- Corresponding author
- Wang, Yuming
- Venue
- Journal of Bioscience and Bioengineering
- Publisher
- Elsevier BV
- Published
- 2014-10
- Volume
- 118
- Issue
- 4
- Pages
- 476-481
- ISSN
- 1347-4421 (ISSN-L)
- 1389-1723
- OpenAlex
- W1965021718
- Cited by
- 360
- References
- 44
- Citations by year
- 2026: 26 · 2025: 40 · 2024: 35 · 2023: 36 · 2022: 42 · 2021: 42 · 2020: 34 · 2019: 33 · 2018: 18 · 2017: 21 · 2016: 19 · 2015: 12 · 2014: 2
- FWCI
- 14.47
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Bioscience and Bioengineering (publishedVersion)
- PubMed (publishedVersion)
- Funders
- the National Key Technology R&D Program (2012BAD33B07)
- National Natural Science Foundation of China (31371757)
- Program for Changjiang Scholars and Innovative Research Team in University (IRT1188)
- Taishan Scholars Programme of Shandong Province
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diet, Metabolism, and Disease
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Keywords
- trimethylamine N-oxide, impaired glucose tolerance, high-fat diet, insulin resistance, hepatic insulin signaling, hepatic gluconeogenesis, hepatic glycogen synthesis, adipose tissue inflammation, MCP-1, IL-10, fasting insulin
- MeSH terms
- Adipose Tissue, Animals, Blood Glucose, Dietary Fats, Fasting, Glucose Tolerance Test, Inflammation, Insulin, Insulin Resistance, Liver, Male, Methylamines, Mice, Inbred C57BL, Interleukin-10, Glucose Intolerance, Chemokine CCL2, Mice, Diet, High-Fat
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