Indeed, impaired glymphatic clearance was previously described in a spontaneously hypertensive rat model 21. In addition, chronic fluid accumulation due to sodium retention within tissue 18, 19 may create a systemic fluid disbalance 20 that could possibly affect glymphatic function. Hypertension is further promoted by impaired endothelial cell function arising due to the chronic metabolic, oxidative, and inflammatory stresses evoked by obesity 15, 16, 17. Furthermore, the adipokine leptin, which normally functions to suppress appetite, is chronically elevated in obesity, and overstimulates the sympathetic nervous system, thereby increasing the risk for hypertension 14.
The development of obesity-related hypertension is linked to increased lipolysis and elevated secretion of adipokines such as angiotensin II and renin that adversely impact vascular tone 13. The flow rate and arterial pulsation are both compromised by hypertension, which is a common complication of obesity 2. Glymphatic fluid flow is driven in part by arterial pulsation 9, 10, 11 such that its transport correlates inversely with heart rate 11, 12. Extracellular fluid carrying metabolic waste products is exported along the perivenous space and cranial and spinal nerves before being collected by meningeal and cervical lymph vessels and returned to the general circulation 8. In this fluid transport pathway, periarterial cerebrospinal fluid (CSF) influx into the parenchyma is facilitated by the water channel aquaporin-4 (AQP4), which is highly expressed in astrocytic endfeet plastered around blood vessels. It is well-established that the brain glymphatic system is suppressed in a broad range of neurodegenerative diseases, including Alzheimer’s disease 6, which may suggest a causal pathway proceeding from obesity.īeing devoid of lymphatic vessels, the brain utilizes a unique brain-wide fluid system for export of metabolic waste, called the glymphatic system 7. Obesity is the leading risk factor for developing hypertension 2, type II diabetes 1 and is further linked to increased risk for developing certain neurodegenerative diseases 3, 4, 5. The prevalence of obesity is rising yearly in children and adolescents around the world 1.
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