Abstract
Upregulated arginase activity, which competes with nitric oxide synthase (NOS), impairs nitric oxide production and has been implicated in various metabolic disorders. This study examined whether circulating amino acid metabolite ratios are associated with arginase and NOS activities and whether arginine bioavailability is associated with metabolic syndrome (MetS). Data related to arginase and NOS activities were collected from non-diabetic Koreans without cardiovascular disease (n = 1998) in the Ansan–Ansung cohorts (2005–2006). Subsequently, correlation and multivariate logistic regression analyses were performed. With the increase in the number of MetS risk factors, ratios of circulating amino acid metabolites, such as those of ornithine/citrulline, proline/citrulline, and ornithine/arginine, also significantly increased, whereas arginine bioavailability significantly decreased. These metabolite ratios and arginase bioavailability were also significantly correlated with MetS risk-related parameters, which remained significant after adjusting for covariates. In addition, logistic regression analysis revealed that high ratios of circulating metabolites and low arginine bioavailability, which indicated increased arginase activity, were significantly associated with a high MetS risk. This study demonstrated that altered ratios of circulating amino acid metabolites indicates increased arginase activity and decreased arginine bioavailability, both of which can be potential markers for MetS risk.
Highlights
The metabolic syndrome (MetS) group had a higher proportion of females, contained older and heavier participants, consumed less alcohol, and smoked fewer cigarettes than the non-MetS group
This study demonstrated that alterations in circulating amino acid metabolite ratios, which are indicative of arginase and nitric oxide synthase (NOS) activities, and arginine bioavailability were significantly associated with
MetS risk: people with high ratios of circulating metabolites and low levels of arginine bioavailability demonstrated high MetS risk. These results suggested that circulating amino acid metabolite ratios, which are indicative of arginase activity and arginine bioavailability can potentially serve as biomarkers for assessing MetS risk
Summary
Metabolic syndrome (MetS) is a continuously increasing global epidemic [1] and a key pathological condition leading to the development of type 2 diabetes (T2DM), cardiovascular disease (CVD) [2,3,4,5,6], and nonalcoholic fatty liver disease [4,6,7,8,9]. Arginase inhibition has been reported to increase the availability of L-arginine to nitric oxide synthase (NOS) pathway for nitric oxide (NO). Our previous study has demonstrated that arginase inhibition ameliorates obesity-induced abnormalities in hepatic lipids, endothelial function, and whole-body adiposity [11,12]. Our previous study has demonstrated that arginase inhibition ameliorates obesity-induced abnormalities in hepatic lipids, endothelial function, and whole-body adiposity and reduce plasma levels ofL-arginine fatty acids and triglycerides (TGs), indicating that it is a potentially [11,12]. The competitive nature of interaction combined NO and citrulline production; this regulates NOS activity and NO (Figure 1) [18,19]. ARG, arginase; NO, nitric oxide; NOS, nitric oxide synthase; OAT, ornithine aminotransferase; P5C, L-pyrroline-5-carboxylate. In reflect arginase and NOS activities, and arginine bioavailability is associated with MetS risk, which can be
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