https://ogma.newcastle.edu.au/vital/access/ /manager/Index ${session.getAttribute("locale")} 5 A gut microbiome metabolite paradoxically depresses contractile function while activating mitochondrial respiration https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:54316 30 µM TMAO in hearts performing minimal isovolumic work, although this response was reduced by >65%. In contrast, exposure to 10 µM or 100 μM TMAO increased mitochondrial complex I, II and maximal respiratory fluxes while appearing to reduce outer membrane integrity. Expression of phosphorylated AMPKα and total GSK-3β declined. Thus, acute exposure of mouse hearts to TMAO levels reported in advanced CVD significantly inhibits cardiac contractility and induces modest coronary constriction while paradoxically overactivating mitochondrial respiration.]]> Wed 28 Feb 2024 15:01:29 AEDT ]]> Circulating TMAO, the gut microbiome and cardiometabolic disease risk: an exploration in key precursor disorders https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:57200 30, n = 27) and Metabolic Syndrome (MetS; ≥ 3 ATPIII report criteria, n = 39). Results: Unexpectedly, plasma [TMAO] did not vary substantially between groups (means of 3–4 µM; p > 0.05), although carnitine was elevated in participants with MetS. Gut microbial diversity and Firmicutes were also significantly reduced in the MetS group (p < 0.05). Exploratory analysis across diverse parameters reveals significant correlations between circulating [TMAO] and seafood intake (p = 0.007), gut microbial diversity (p = 0.017–0.048), and plasma [trimethylamine] (TMA; p = 0.001). No associations were evident with anthropometric parameters or cardiometabolic disease risk. Most variance in [TMAO] within and between groups remained unexplained. Conclusions: Data indicate that circulating [TMAO] may be significantly linked to seafood intake, levels of TMA substrate and gut microbial diversity across healthy and early disease phenotypes. However, mean concentrations remain < 5 µM, with little evidence of links between TMAO and cardiometabolic disease risk. These observations suggest circulating TMAO may not participate mechanistically in cardiometabolic disease development, with later elevations likely a detrimental sequela of extant disease.]]> Fri 21 Feb 2025 14:18:50 AEDT ]]>