2. Academic Validation
  3. Long-term high-fat diet increases glymphatic activity in the hypothalamus in mice

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

  • Sci Rep. 2023 Mar 13;13(1):4137. doi: 10.1038/s41598-023-30630-y.
Christine Delle # 1,  Neža Cankar # 1,  Christian Digebjerg Holgersson 1,  Helle Hvorup Knudsen 1,  Elise Schiøler Nielsen 1,  Celia Kjaerby 1,  Yuki Mori 1,  Maiken Nedergaard 2 3,  Pia Weikop 1
Affiliations

Affiliations

  • 1 Center for Translational Neuromedicine, Faculty of Medical and Health Sciences, University of Copenhagen, Blegdamsvej 3B, 2200, Copenhagen N, Denmark.
  • 2 Center for Translational Neuromedicine, Faculty of Medical and Health Sciences, University of Copenhagen, Blegdamsvej 3B, 2200, Copenhagen N, Denmark. [email protected].
  • 3 Center for Translational Neuromedicine, University of Rochester Medical School, Elmwood Avenue 601, Rochester, NY, 14642, USA. [email protected].
  • # Contributed equally.
PMID: 36914703 DOI: 10.1038/s41598-023-30630-y
Abstract

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.

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