The interactions between energy homeostasis and neurovascular plasticity.

Food intake and energy expenditure are sensed and processed by multiple brain centres to uphold energy homeostasis. Evidence from the past decade points to the brain vasculature as a new critical player in regulating energy balance that functions in close association with the local neuronal networks. Nutritional imbalances alter many properties of the neurovascular system (such as neurovascular coupling and blood-brain barrier permeability), thus suggesting a bidirectional link between the nutritional milieu and neurovascular health. Increasing numbers of people are consuming a Western diet (comprising ultra-processed food with high-fat and high-sugar content) and have a sedentary lifestyle, with these factors contributing to the current obesity epidemic. Emerging pharmacological interventions (for example, glucagon-like peptide 1 receptor agonists) successfully trigger weight loss. However, whether these approaches can reverse the detrimental effects of long-term exposure to the Western diet (such as neurovascular uncoupling, neuroinflammation and blood-brain barrier disruption) and maintain stable body weight in the long-term needs to be clarified in addition to possible adverse effects. Lifestyle interventions revert the nutritional trigger for obesity and positively affect our overall health, including the cardiovascular system. This Perspective examines how lifestyle interventions affect the neurovascular system and neuronal networks.

Central myelin dysfunction bridges obesity and neurological diseases.

The central nervous system (CNS) relies on myelin for proper functioning. Myelin remodeling is a risk factor for neurometabolic and endocrine malfunction, resulting in cognitive decline and heightened susceptibility to neurological diseases. The plasticity of myelin upon nutrient shifts may lead to dietary and hormonal interventions for preventing and treating neural complications.

Maternal nutritional programming shapes the cerebral landscape.

The escalating prevalence of maternal obesity raises concerns about its influence on offspring health. Exposure to obesogenic environments during early development leads to persistent alterations in brain function contributing to neurological disorders. Nutritional programming emerges as a promising avenue to counteract the deleterious effects of maternal obesity on offspring neurodevelopment.

Lipid droplets and peroxisomes are co-regulated to drive lifespan extension in response to mono-unsaturated fatty acids.

Dietary mono-unsaturated fatty acids (MUFAs) are linked to longevity in several species. But the mechanisms by which MUFAs extend lifespan remain unclear. Here we show that an organelle network involving lipid droplets and peroxisomes is critical for MUFA-induced longevity in Caenorhabditis elegans. MUFAs upregulate the number of lipid droplets in fat storage tissues. Increased lipid droplet number is necessary for MUFA-induced longevity and predicts remaining lifespan. Lipidomics datasets reveal that MUFAs also modify the ratio of membrane lipids and ether lipids-a signature associated with decreased lipid oxidation. In agreement with this, MUFAs decrease lipid oxidation in middle-aged individuals. Intriguingly, MUFAs upregulate not only lipid droplet number but also peroxisome number. A targeted screen identifies genes involved in the co-regulation of lipid droplets and peroxisomes, and reveals that induction of both organelles is optimal for longevity. Our study uncovers an organelle network involved in lipid homeostasis and lifespan regulation, opening new avenues for interventions to delay aging.

A low-cost device for cryoanesthesia of neonatal rodents.

Studying the development of neural circuits in rodent models requires surgical access to the neonatal brain. Since commercially available stereotaxic and anesthetic equipment is designed for use in adults, reliable targeting of brain structures in such young animals can be challenging. Hypothermic cooling (cryoanesthesia) has been used as a preferred anesthesia approach in neonates. This commonly involves submerging neonates in ice, an approach that is poorly controllable. We have developed an affordable, simple to construct device - CryoPup - that allows for fast and robust cryoanesthesia of rodent pups. CryoPup consists of a microcontroller controlling a Peltier element and a heat exchanger. It is capable of both cooling and heating, thereby also functioning as a heating pad during recovery. Importantly, it has been designed for size compatibility with common stereotaxic frames. We validate CryoPup in neonatal mice, demonstrating that it allows for rapid, reliable and safe cryoanesthesia and subsequent recovery. This open-source device will facilitate future studies into the development of neural circuits in the postnatal brain.