An increase in adenosine-5'-triphosphate (ATP) content in rostral ventrolateral medulla is engaged in the high fructose diet-induced hypertension.
BACKGROUND
The increase in fructose ingestion has been linked to overdrive of sympathetic activity and hypertension associated with the metabolic syndrome. The premotor neurons for generation of sympathetic vasomotor activity reside in the rostral ventrolateral medulla (RVLM). Activation of RVLM results in sympathoexcitation and hypertension. Neurons in the central nervous system are able to utilize fructose as a carbon source of ATP production. We examined in this study whether fructose affects ATP content in RVLM and its significance in the increase in central sympathetic outflow and hypertension induced by the high fructose diet (HFD).


RESULTS
In normotensive rats fed with high fructose diet (HFD) for 12 weeks, there was a significant increase in tissue ATP content in RVLM, accompanied by the increases in the sympathetic vasomotor activity and blood pressure. These changes were blunted by intracisternal infusion of an ATP synthase inhibitor, oligomycin, to the HFD-fed animals. In the catecholaminergic-containing N2a cells, fructose dose-dependently upregulated the expressions of glucose transporter 2 and 5 (GluT2, 5) and the rate-limiting enzyme of fructolysis, ketohexokinase (KHK), leading to the increases in pyruvate and ATP production, as well as the release of the neurotransmitter, dopamine. These cellular events were significantly prevented after the gene knocking down by lentiviral transfection of small hairpin RNA against KHK.


CONCLUSIONS
These results suggest that increases in ATP content in RVLM may be engaged in the augmented sympathetic vasomotor activity and hypertension associated with the metabolic syndrome induced by the HFD. At cellular level, the increase in pyruvate levels via fructolysis is involved in the fructose-induced ATP production and the release of neurotransmitter.
Center for Translational Research in Biomedical Sciences, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Kaohsiung 83301, Taiwan. klhwu@adm.cgmh.org.tw.
Kay L H
KL
Wu
Chun-Ying
CY
Hung
Julie Y H
JY
Chan
Chih-Wei
CW
Wu
D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D001794:Blood Pressure / Q000235:genetics; D004032:Diet; D005632:Fructose / Q000008:administration & dosage*; D006339:Heart Rate; D006973:Hypertension / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism*; D008526:Medulla Oblongata / Q000378:metabolism; D018384:Oxidative Stress / Q000235:genetics*; D051381:Rats; D013564:Sympathetic Nervous System / Q000378:metabolism; D014666:Vasomotor System / Q000378:metabolism
D005632:Fructose; D000255:Adenosine Triphosphate