The brain is the body’s command centre, and neurons are the workhorses that carry out its commands. They transmit signals that regulate many bodily functions, including key metabolic processes such as appetite, body weight and energy expenditure.
But how do neurons power all this activity?
Until now, it was thought they relied primarily on glucose. However, a new Canadian study published in Nature Metabolism challenges this view, showing that neurons maintain lipid reserves in the form of lipid droplets, which are crucial to their functioning.
The study was supervised by Thierry Alquier, a professor in Université de Montréal’s Faculty of Medicine and researcher at the UdeM-affiliated CHUM Research Centre (CRCHUM), and Elizabeth Rideout, an associate professor in the Faculty of Medicine at the University of British Columbia. Doctoral students Romane Manceau and Danie Majeur worked on the study.
Role poorly understood
For years, scientists believed that lipids in neurons primarily serve a structural role, maintaining membranes and supporting internal functions.
While studies had identified a specific storage form known as lipid droplets—organelles composed mainly of triglycerides—they were mostly observed in pathological contexts, particularly in neurodegenerative diseases such as Alzheimer’s. Their presence in healthy neurons and role in everyday neuronal function were poorly understood.
Using a combination of animal models and genetic tools, Alquier and his team demonstrated that lipid droplets are present and functional in the neurons of species separated by vast evolutionary distances, from invertebrates to vertebrates.
To investigate the role of lipid droplets in neuronal activity, he and his co-researchers focused on two types of neurons involved in energy balance: AgRP hypothalamic neurons in mice and AKH neuroendocrine neurons in fruit flies.
The scientists identified the enzymes and proteins that regulate the formation and use of lipid droplets in these neurons. By introducing genetic mutations that disrupted these components, the research team blocked the neurons’ access to their lipid stores.
