Long-term high-fat diet increases glymphatic activity in the hypothalamus in mice

Obesity affects millions of people worldwide and is associated with an increased risk of cognitive decline. The glymphatic system is a brain-wide metabolic waste clearance system, dysfunction of which is linked to dementia. We herein examined glymphatic transport in mice with long-term obesity induced by a high-fat diet for 10 months. The obese mice developed hypertension and elevated heart rate, neuroinflammation and gliosis, but not apparent systemic inflammation. Surprisingly, glymphatic inflow was globally unaffected by the high-fat diet except for the hypothalamus, which displayed increased influx and elevated AQP4 vascular polarization compared to the normal weight control group. We propose that a long-term high-fat diet induced metabolic alteration of hypothalamic neurons and neuroinflammation, which in turn enhanced glymphatic clearance in the effected brain region.

Automated summary

Obesity is associated with increased risk of cognitive decline, and this study investigated the glymphatic transport in mice with long-term obesity induced by high-fat diet. The results showed that although the obese mice developed hypertension, elevated heart rate, neuroinflammation, and gliosis, the glymphatic inflow was globally unaffected except in the hypothalamus. It suggests that long-term high-fat diet induced metabolic alteration and neuroinflammation in the hypothalamus, leading to enhanced glymphatic clearance in this specific brain region.