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Clinical Trial
. 2016 May 27:6:26745.
doi: 10.1038/srep26745.

Relationship of Serum Trimethylamine N-Oxide (TMAO) Levels with early Atherosclerosis in Humans

Elko Randrianarisoa  1   2 , Angela Lehn-Stefan  1   2   3 , Xiaolin Wang  4 , Miriam Hoene  1   2 , Andreas Peter  1   2   3 , Silke S Heinzmann  3   5 , Xinjie Zhao  4 , Ingmar Königsrainer  6 , Alfred Königsrainer  6 , Bernd Balletshofer  1 , Jürgen Machann  2   3 , Fritz Schick  2   3   7 , Andreas Fritsche  1   2   3 , Hans-Ulrich Häring  1   2   3 , Guowang Xu  4 , Rainer Lehmann  1   2   3 , Norbert Stefan  1   2   3
Affiliations
Clinical Trial

Relationship of Serum Trimethylamine N-Oxide (TMAO) Levels with early Atherosclerosis in Humans

Elko Randrianarisoa et al. Sci Rep. .

Abstract

Circulating trimethylamine N-Oxide (TMAO) levels predict cardiovascular disease (CVD), possibly by impacting on cholesterol metabolism and oxidative stress. Because hepatic TMAO production is regulated by insulin signalling and it is unclear whether and to what extent circulating TMAO levels associate with CVD risk, independently of insulin resistance and its important determinants fatty liver and visceral obesity, we have now addressed this question in 220 subjects who participated in the Tübingen Lifestyle Intervention Program. Visceral fat mass (r = 0.40, p < 0.0001), liver fat content (r = 0.23, p = 0.0005) and TMAO levels (r = 0.26, p < 0.0001) associated positively, and insulin sensitivity associated negatively (r = -0.18, p = 0.009) with carotid intima-media thickness (cIMT). Higher TMAO levels (std.-Beta 0.11, p = 0.03) predicted increased cIMT, independently of age, sex and visceral fat mass. While during the lifestyle intervention most cardiovascular risk parameters improved, mean TMAO levels did not change (p = 0.18). However, cIMT decreased significantly (p = 0.0056) only in subjects in the tertile with the largest decrease of TMAO levels (>20%). We provide novel information that increased serum TMAO levels associate with increased cIMT, independently of established cardiovascular risk markers, including insulin resistance, visceral obesity and fatty liver. Furthermore, the decrease of cIMT during a lifestyle intervention may be related to the decrease of TMAO levels.

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Figures

Figure 1
Figure 1. Cross-sectional relationship of fasting serum TMAO levels with cIMT.
Univariate cross-sectional relationship (Pearson correlation coefficient and p-value) of fasting serum trimethylamine N-Oxide (TMAO) levels with carotid intima-media thickness (cIMT) in 220 subjects.
Figure 2
Figure 2. Change of TMAO levels and change of cIMT during 9 months of lifestyle intervention.
Individual carotid intima-media thickness (cIMT) before and after 9 months of lifestyle intervention according to tertiles of changes in fasting serum trimethylamine N-Oxide (TMAO) levels (p-value from the paired t test) in 220 subjects.
Figure 3
Figure 3. Relationships of hepatic FMO3 mRNA expression with sex, age and adjusted HOMA-IR.
Relationship of hepatic FMO3 mRNA expression (normalized for the mRNA expression of the housekeeping gene RSP13) with gender (A) and age (B) and of hepatic FMO3 mRNA expression, adjusted for sex and gender, with the homeostatic model assessment of insulin resistance (HOMA-IR) in 55 patients who donated liver samples (C).
See this image and copyright information in PMC

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