Abstract 1374: Sympathetic Overactivity Precedes Metabolic Dysfunction In Insulin Resistant Mice
The mechanisms that underlie the relationship between metabolic syndrome and cardiovascular dysfunction are unclear. The increasing incidence of diabetes and cardiovascular disease may be related to dietary changes, including consumption of high levels of fructose. The aim was to investigate the time course of the metabolic and cardiovascular alterations induced by fructose overload in the drinking water (100 g/L). C57/BL mice were divided into 3 groups: controls (C); 15 days-fructose (F15); and 60 days-fructose (F60). Mice were instrumented with radiotelemetric arterial catheters to light/dark pattern of systolic arterial pressure (SAP) and SAP variability measurement. Plasma glucose, lipids, insulin, leptin and glucose tolerance were also quantified. Fructose mice showed higher SAP at 15 and 60 days during both the light (F15: 123±2 and F60:118±2 mmHg) and dark periods (F15: 136±4 and F60: 136±5 mmHg) as compared to controls (light: 111±2 and dark: 117±2 mmHg). SAP variance (VAR) was unchanged at F15, but was increased at F60 (light: 18±3 and dark: 37±7 ms2) in relation to C group (light: 6±1 and dark: 14±1ms2). The low frequency component (LF) of SAP variability was enhanced in the light and dark periods in fructose groups as compared to controls. Metabolic parameters were unchanged at day 15 day. After 60 days of fructose, there were significant increases in plasma glucose (26%), cholesterol (44%), triglycerides (22%), insulin (95%), leptin (63%) as well as glucose intolerance. The LF component of SAP VAR was positively correlated with SAP and VAR after 15 (r=0.84 and r=0.95) and 60 days (r=0.87 and r=0.92). The plasma leptin was associated with body weight and the glucose tolerance (AUC) after 15 (r=0.85 and r=0.8) and 60 days (r=0.8 and r=0.87) as well as with plasma insulin (r=0.8) after 60 days. The increases in plasma insulin and leptin indicate that this mouse model of fructose loading in the drinking water is similar to the human condition of type2 diabetes. The results also show that increased sympathetic activity preceded metabolic dysfunction in fructose fed mice, suggesting that sympathetic overactivity may be a key mechanism underling the cluster of cardiovascular and metabolic symptoms associated with metabolic syndrome.