Abstract P149: Distinct Profiles of Brain Medullary Metabolites Detected by 1 H-Magnetic Resonance Spectroscopy Correlate with Indices of Autonomic Function and Visceral Fat in Healthy Adults

Abstract

Higher forebrain myoinositol (mIns), a marker of glial inflammation/proliferation as detected by proton magnetic resonance spectroscopy (MRS), correlates with systemic inflammation. Elevated circulating markers of inflammation are associated with lower baroreceptor reflex sensitivity (BRS) and heart rate variability (HRV) as well as visceral fat or central obesity. To determine whether transmitters/metabolites in a cardiovascularly (CV) relevant brain region correlate with age-related declines in BRS and HRV and markers of abdominal fat, autonomic profiles were determined by spectral and sequence analysis from continuous blood pressure and HR values in the supine position of healthy subjects 22 - 76 yrs old (12F, 4M); subjects later underwent a single voxel (10 x 7 x 20mm) proton MRS scan of dorsal medulla on a 3T magnet (n = 11; 9F, 2M) and measures of abdominal fat by computerized tomography (CT) (n = 9; 7F,2M). The mean arterial pressure was 88 ± 3 mm Hg, HR 64 ± 3 beats/min and BMI 27 ± 1 kg/m 2 . Glutamate (Glu) correlated directly with vagal (HF RRI r = 0.72, p < 0.02) and inversely with sympathetic (LF RRI r = -0.72, p < 0.02) control of HR. Markers of Glu metabolism and neuronal integrity/activity, N-acetyl-aspartate acid (NAA) + N-acetyl aspartyl glutamate (NAAG), did not correlate with age, but did correlate inversely with BRS (Seq ALL: r = -0.69, P < 0.02), HRV (rMSSD: r = -0.76, p < 0.008) and directly with HR (r = 0.68, p < 0.03). Total visceral fat had a negative correlation with BRS (Seq Up: r = -0.70, p < 0.02). mIns and markers of demyelination and reduced axonal integrity such as Glycerophosphocholine (GPC) and total choline containing compounds (GPC+PCh) exhibited striking positive correlations with percent visceral fat (r = 0.97, 0.81 and 0.82, P < 0.02). BMI and GPC correlated with HR (r = 0.55, 0.72, p < 0.04), but neither these nor mIns or choline compounds correlated with autonomic function. Thus, in healthy adults, Glu concentration in dorsal medulla directly correlates with cardiac vagal function, whereas markers of Glu metabolism inversely correlate with BRS and HRV. In contrast, markers of glial inflammation directly associate with increases in visceral adiposity, but not autonomic dysfunction. P30-AG21332, Farley Hudson, Hypertension & Vasc Res Ctr