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OVEREXPRESSION OF UCP4 IN ASTROCYTES INDUCES FATTY ACID OXIDATION FOR MITOCHONDRIA RESPIRATION FUELLING
Simone Crivelliand 2 co-authors
University of Lausanne
FENS Forum 2026 (2026)
Barcelona, Spain
Board PS04-08PM-227
Presentation
Date TBA
Board: PS04-08PM-227
Event Information
Poster Board
PS04-08PM-227
Poster
View posterAbstract
A growing body of evidence recognizes astrocytes’ ability to oxidize fatty acids as an energy substrate, a process that appears critical for higher-order cerebral functions. However, the signals that reprogram astrocytes from primarily glycolytic metabolism to fatty acid utilization remain unclear. Here, we provide the first evidence that increased expression of mitochondrial uncoupling protein 4 (UCP4) in primary astrocytes induces a metabolic shift favoring β-oxidation. UCP4 overexpression upregulate genes associated with fatty acid uptake, synthesis, transport, and metabolism, enabling fatty acids to fuel mitochondrial respiration while redirecting glucose-derived pyruvate toward lactate production. This astrocytic metabolic shift prevented neurodegeneration in the familial Alzheimer’s disease mouse model 5xFAD. Mice treated with an adeno-associated virus (AAV) overexpressing UCP4 did not develop memory impairments at 6 months of age. Moreover, brain levels of Aβ1-42 as well as synaptic markers such as PSD95 were rescued. Our data suggest that inducing a metabolic shift toward β-oxidation could provide a biological framework for developing treatments for neurodegenerative diseases such as AD.
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