TMAO, a seafood-derived molecule, produces diuresis and reduces mortality in heart failure rats

Abstract

<jats:p>Trimethylamine-oxide (TMAO) is present in seafood which is considered to be beneficial for health. Deep-water animals accumulate TMAO to protect proteins, such as lactate dehydrogenase (LDH), against hydrostatic pressure stress (HPS). We hypothesized that TMAO exerts beneficial effects on the circulatory system and protects cardiac LDH exposed to HPS produced by the contracting heart. Male, Sprague-Dawley and Spontaneously-Hypertensive-Heart-Failure (SHHF) rats were treated orally with either water (control) or TMAO. In vitro, LDH with or without TMAO was exposed to HPS and was evaluated using fluorescence correlation spectroscopy. TMAO-treated rats showed higher diuresis and natriuresis, lower arterial pressure and plasma NT-proBNP. Survival in SHHF-control was 66% vs 100% in SHHF-TMAO. In vitro, exposure of LDH to HPS with or without TMAO did not affect protein structure. In conclusion, TMAO reduced mortality in SHHF, which was associated with diuretic, natriuretic and hypotensive effects. HPS and TMAO did not affect LDH protein structure.</jats:p>

Microbiota-Derived Metabolite Trimethylamine N-Oxide Protects Mitochondrial Energy Metabolism and Cardiac Functionality in a Rat Model of Right Ventricle Heart Failure

“…Consistent with these findings, our study shows that TMAO administration can partially prevent right ventricular hypertrophy as shown by normalized organ-to-body weight indexes and hypertrophy-related gene expression. Moreover, consistent with our results, protective effects of TMAO were also observed in Spontaneously Hypertensive Heart Failure rats, in which long-term TMAO treatment improved survival and cardiac parameters and lowered plasma NT-proBNP levels (Gawrys-Kopczynska et al, 2020 ). Similarly, in our study, TMAO administration preserved right ventricular function, as indicated by normalized direct RV pressure and RV fractional area change; moreover, TMAO decreased the expression of a marker of heart failure severity, BNP, in right ventricular tissue.…”

“…The protective role of TMAO was previously explained by its ability to reduce endoplasmic reticulum stress (Makhija et al, 2014 ), oxidative-nitrative stress and the subsequent vascular and diabetic complications (Lupachyk et al, 2013 ; Fukami et al, 2015 ). More recently, some protective effects were attributed to the ability of TMAO to increase diuresis and natriuresis (Gawrys-Kopczynska et al, 2020 ). In addition, our study proposes preserved cardiac energy metabolism as a possible mechanism underlying the observed protective effects of TMAO.…”

“…On the other hand, the Mediterranean diet, which is focused on regular consumption of TMAO-rich fish and seafoods (Cho et al, 2017 ), is inversely correlated with fatal coronary heart disease (He et al, 2004 ) and is proposed to be a strategy for preventing and reducing the risk of cardiovascular and metabolic diseases (Tørris et al, 2014 ; Widmer et al, 2015 ; Estruch et al, 2018 ). Moreover, it was recently shown that chronic treatment with low-dose TMAO was associated with preserved cardiac hemodynamic parameters in Spontaneously Hypertensive rats and Spontaneously Hypertensive Heart Failure rats (Huc et al, 2018 ; Gawrys-Kopczynska et al, 2020 ). Such controversial results raise the question of whether increased availability of TMAO plays detrimental or protective roles in the progression of cardiovascular diseases.…”

Association of Urinary and Plasma Levels of Trimethylamine N-Oxide (TMAO) with Foods

“…The increase in plasma TMAO in CVD may be similar to that observed for plasma natriuretic peptide B, which is considered a marker of CVD risk but also a compensatory response that results in beneficial effects for the overloaded heart. Thus, a recent study in animal models has shown that a TMAO supplementation could even be beneficial in counteracting hypertension-related heart failure [ 51 ]. Similarly, in another recent review it was suggested that TMAO elevation may be a compensatory mechanism in response to disease.…”

The Accumulation and Molecular Effects of Trimethylamine N-Oxide on Metabolic Tissues: It’s Not All Bad

“…Contrary to the deleterious TMAO effects observed in CKD, TMAO shows positive and negative effects on kidney function in the context of CVD. During a 58-week study on rats modeling heart failure, all the rats supplemented with TMAO with about 40µM serum levels survived whereas 3 of the un-supplemented group died from ischemic stroke or lung edema [ 202 ]. This increased survival corresponded with increased diuresis.…”