Biogenic Amines and Inflammatory Status in Nascent Metabolic Syndrome

Objective Metabolic syndrome (MetS) is a cardio‐metabolic cluster that predisposes individuals to an increased risk for cardiovascular disease (CVD) and type‐2 diabetes (T2DM). It afflicts 35% of the American adult population and is expected to increase globally. Studies suggest that biogenic amines have implications in CVD and T2DM. Specifically, an increased level of Trimethylamine N‐oxide (TMAO), a choline and L‐carnitine derived metabolite, may exacerbate glucose tolerance, inhibit hepatic insulin signaling, and increase inflammation and atheroma burden in CVD. Glutamate may also have a role in obesity and insulin resistance. However, the precise role of these biogenic amines has recently been called into question. The aim of this exploratory study was to evaluate the levels of choline, L‐carnitine, TMAO, and glutamate in early morning urine samples of MetS patients without CVD or T2DM compared to matched controls. We also characterize how these amines correlate with markers of inflammation and adipokines, since inflammation has well‐established implications in MetS, CVD, and T2DM. Methods Subjects' ages ranged from 24 to 72 years, and MetS (n=30) and healthy controls (n=20) were evaluated. MetS was defined by the Adult Treatment Panel III criteria, with patients needing to have 3 of the 5 characteristics of increased triglycerides, low HDL‐cholesterol, plasma glucose of 100–125 mg/dl, increased waist circumference, and hypertension. All patients had normal renal and hepatic function. Samples were prepared from patient's frozen urine samples at −70 degrees C, and were quantified by the NIH West Coast Metabolomics center using standardized chromatography/mass spectrometry techniques. Metabolites were compared to external standards and quantified by peak intensities. All metabolites were normalized to urine creatinine levels. We also analyzed correlations between these biogenic amines to the following inflammatory parameters: hsCRP, IL‐1b, IL‐6, TNF, IL‐10, IL‐8, TLR‐2, TLR‐4, sTNFR1, sTNFR2, endotoxin, chemerin, leptin and adiponectin. Results Compared to controls, MetS patient had a statistically significant increase in L‐carnitine (p=0.0002) and a reduction in glutamate levels (p=0.0001). Additionally, there was a trend of significant increase in TMAO levels (p=0.08), while choline was not significantly altered in MetS. We also made a novel observation that triethanolamine was significantly reduced in nascent MetS compared to controls (p=0.0005). In addition, L‐carnitine correlated significantly with sTNFR1 and leptin, and inversely to adiponectin. TMAO was associated with IL‐6, endotoxin, and chemerin. Glutamate was inversely related to TMAO and L‐carnitine, as well as the inflammatory markers IL‐6 and endotoxin. While glucose, HBA1C, and HOMA‐IR were significantly increased in MetS, only glucose levels correlated with L‐carnitine. Conclusions Collectively our novel results suggest that L‐carnitine is directly, while glutamate is inversely, correlated with markers of inflammation in nascent MetS. Cellular L‐carnitine and glutamate could be biomarkers or direct biomediators of inflammation in the pathogenesis of MetS, and sequelae of CVD and T2DM. This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .