Imaging Appetite

Acknowledgements Authors are indebted to Dr. Diana Quiñones Tapia for expert neuroradiological assistance during the human studies and to Mr. Javier Pérez CSIC, for careful, professional drafting of the illustrations. Abstract Hypothalamic appetite regulation is a vital homeostatic process underlying global energy balance in animals and humans, its disturbances resulting in feeding disorders with high morbidity and mortality. The objective evaluation of appetite remains difficult, very often restricted to indirect measurements of food intake and body weight. We report here, the direct, non invasive visualization of hypothalamic activation by fasting using Diffusion Weighted Magnetic Resonance Imaging, in the mouse and human brains. The brain of fed or fasted mice or humans were imaged at 7 or 1,5 Tesla, respectively, by diffussion weighted magnetic resonance imaging using a complete range of b values (10<b<1800 s.mm-2). The diffusion weighted image data sets were registered and analyzed pixel by pixel using a biexponetial model of diffusion, or a model-free Linear Discriminant Analysis approach. Biexponetial fittings revealed statistically significant increases in the slow diffusion parameters of the model, consistent with a neurocellular swelling response in the fasted hypothalamus. Linear Discriminant Analysis was able to classify successfully the diffusion data sets from mice and humans between fed and fasted states, suggesting intrinsic differences supplementary to those detected by the alternative biexponential model. Our results are consistent with increased glutamatergic neurotransmission during orexigenic firing, a process resulting in increased ionic accumulation and concomitant osmotic neurocellular swelling. This swelling response,is spatially extendable through surrounding astrocytic networks until it becomes MRI detectable. Present findings open new avenues for the direct, non invasive, evaluation of appetite disorders and other hypothalamic pathologies helping potentially in the development of the corresponding therapies.