The modulation of appetite, satiation and food intake stems from the interplay of central mechanisms of homeostasis, hedonism and cognitive control, receiving and integrating information on energy balance and feeding status of the body from peripheral organs, including dietary and gut-related signals. Obesity is a phenotype, likely resulting from the dysregulation of one or more of the above mechanisms. Different mechanisms may prevail in different people, though leading to a similar phenotype. The recognition of such diversity would offer opportunities for personalized treatment. This lecture will present data from a study conducted in well characterized overweight women, undergoing brain imaging of glucose metabolism to detect cerebral reactions to sensory food stimuli. The study suggests that women with food addictive behavior have a specific pattern of activation, which implicates cognitive control and diet-related factors (hormones, substrates, and possibly microbiota) in their food seeking behavior. This hypothesis is supported by the characterization of feeding behavior and brain and brown adipose tissue (BAT) metabolism in mice models of neurodegenerative disease and/or high-fat feeding, also in combination with intranasal insulin therapy. In order to better define the sequence of events linking brain function and feeding behavior, studies in the offspring of obese mothers are addressed, since maternal obesity represents a preventable condition, in which the factors above are affected since early life in the offspring. Results in humans, and animal models will be presented. Cumulatively, our studies suggest that a hypermetabolic brain, deriving from metabolic disturbances or high-fat dietary exposure may be an early detrimental factor, and a hypometabolic brain reflecting neuronal loss may enhance food intake, but also BAT browning. Substrates, hormones and gut microbes can promote a vicious cycle.
20 - 23 May 2017
European Society of Endocrinology