Ratio of serum levels of AGEs to soluble RAGE is correlated with trimethylamine-N-oxide in non-diabetic subjects

Abstract

Trimethylamine (TMA), an intestinal microflora-dependent metabolite formed from phosphatidylcholine- and L-carnitine-rich food, such as red meat, is further converted to trimethylamine-N-oxide (TMAO), which could play a role in cardiometabolic disease. Red meat-derived products are one of the major environmental sources of advanced glycation end products (AGEs) that may also contribute to the pathogenesis of cardiometabolic disorders through the interaction with receptor for AGEs (RAGE). However, the relationship among AGEs, soluble form of RAGE (sRAGE) and TMAO in humans remains unclear. Non-diabetic subjects underwent a physical examination, determination of blood chemistry and anthropometric variables, including AGEs, sRAGE, TMA and TMAO. Multiple regression analyses revealed that HbA1c, uric acid and AGEs were independently associated with log TMA, whereas log AGEs to sRAGE ratio and statin non-use were independently correlated with log TMAO. Our present findings indicated that AGEs to sRAGE ratio was correlated with log TMAO, a marker of cardiometabolic disorders.

Keywords:

• TMA
• TMAO
• AGEs
• RAGE
• atherosclerosis

Acknowledgements

We thank Mami Nakayama, Miho Nakao-Kogure, Katsue Shiramizu, Miyuki Nishikata and Makiko Kiyohiro, Department of Medicine, Division of Cardiovascular Medicine, Kurume University School of Medicine; and Nanako Mitsuhashi and Marika Ikuma, Laboratory of Drug Metabolism and Pharmacokinetics, Showa Pharmaceutical University, for their excellent technical assistance.

Disclosure statement

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.

Additional information

Funding

This study was supported in part by grants from the Kimura Memorial Foundation (A.T. and Y.N.); the Ishibashi Foundation for the Promotion of Science (N.T.); the Mitsui Life Social Welfare Foundation (N.T.); and the Grant-in-Aid for Scientific Research (C) (Grant Number 26461097) (N.T.) and (B) (Grant Number 25293127) (S.I.) from the Ministry of Education, Culture, Sports, Science and Technology, Japan.