Background. Given the heightened tolerance to self-starvation in anorexia nervosa, a hypothalamic dysregulation of energy and glucose homeostasis has been hypothesized. Therefore, we investigated whether hypothalamic reactivity to glucose metabolism is impaired in AN. Methods. Twenty-four participants with AN, 28 normal-weight and 24 healthy participants with obesity underwent 2 magnetic resonance imaging (MRI) sessions in a single-blind, random-order, case-controlled crossover design. We used an intragastric infusion of glucose and water to bypass the cephalic phase of food intake. The responsivity of the hypothalamus and the crosstalk of the hypothalamus with reward-related brain regions were investigated using high-resolution MRI. Results. Normal-weight control participants displayed the expected glucose-induced deactivation of hypothalamic activation, whereas patients with AN and participants with obesity showed blunted hypothalamic reactivity. Compared to normal-weight and obese controls, patients with AN failed to show functional connectivity between the hypothalamus and reward-related brain regions during water relative to glucose. Finally, patients with AN displayed typical baseline levels of peripheral appetite hormones during a negative energy balance. Conclusion. These results indicate that blunted hypothalamic glucose reactivity might be related to the pathophysiology of AN. This provides new insights for future research, as it is an extended perspective of the traditional primary nonhomeostatic understanding of the disease. Funding. This study was supported by a grant from the DFG (SI 2087/2-1).
Joe J. Simon, Marion A. Stopyra, Esther Mönning, Sebastian C. A. M. Sailer, Nora Lavandier, Lars Kihm, Martin Bendszus, Hubert Preissl, Wolfgang Herzog, Hans-Christoph Friederich