High Salt Diet May Stimulate Fructose Uptake in Brain Neurons and Contribute to Neuronal Apoptosis

Abstract

Clinical studies have been leaning toward the role that the central nervous system (CNS) is one of the main controls of blood pressure regulation such as the onset of fructose‐induced hypertension. The CNS is by far the most energy demanding and consuming organ in our body and it can metabolize fructose but that has consequences. However, the connection between fructose and hypertension within the CNS is still lacking in definition. Here we tested the hypothesis that a high fructose diet contributes to hypertension via increase neuronal apoptosis. Eight‐week‐old male Sprague Dawley (SD) rats were divided into 4 groups and were fed a normal salt (NS: 0.4% NaCI chow), high salt (HS: 4% NaCl chow), NS diet with fructose (F: 20% fructose drinking water), and high salt plus fructose (HS+F: 4%NaCl chow and 20% drinking water) diet, respectively, for 3 consecutive weeks. Their blood pressure was measured prior and post each diet treatment using the non‐invasive tail‐cuff technologies. All rats were then euthanized, then their blood and cerebrospinal fluid (CSF) was withdrawn for fructose measurements. HS+F rats showed an increase in mean arterial blood pressure (MAP) 126 mmHg compared to control 90 mmHg (p<0.0001). There is no significant MAP alterations in HS or F alone groups compared to NS group. Fructose measurement demonstrated that the serum fructose concentration is significantly increased in the F group (359 μM), and HS+F (409 μM) compared to control NS group (253 μM), while no significant alterations were observed in serum fructose in HS alone group (229 μM). In contrast, CSF fructose concentration is dramatically decreased in F (230 μM) and HS+F (231 μM) groups compared to NS control group (290 μM). In addition, immunostaining showed that HS+F group significantly promoted immunoreactivity of GLUT5, a fructose transporter in the brain paraventricular nucleus (PVN). Furthermore, incubation of brain neurons isolated from neonatal SD rats with 1 mM fructose for 6 hours stimulated neuronal apoptosis (27%) compared to the control (20%, P<0.05). In summary, this study demonstrated that HS+F diet decreases CSF fructose concentration, increases PVN GLUT5 expression, and results in hypertension in normal SD rats. These results suggest that HS facilitates brain neurons to uptake fructose into neuronal cells, resulting in an increase in intracellular fructose, which in turn, stimulate cell apoptosis. Increased neuronal apoptosis may contribute to hypertension.Support or Funding InformationFunding support: R15‐HL122952, Qinghui Chen; R15‐HL129213, Zhiying Shan; Michigan Tech and portage health Foundation REF, Zhiying ShanThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.