Neuroimaging of hypothalamic mechanisms related to glucose metabolism in anorexia nervosa and obesity
Joe J. Simon, Marion A. Stopyra, Esther Mönning, Sebastian Sailer, Nora Lavandier, Lars P. Kihm, Martin Bendszus, Hubert Preissl, Wolfgang Herzog, Hans-Christoph Friederich
Joe J. Simon, Marion A. Stopyra, Esther Mönning, Sebastian Sailer, Nora Lavandier, Lars P. Kihm, Martin Bendszus, Hubert Preissl, Wolfgang Herzog, Hans-Christoph Friederich
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Clinical Research and Public Health Metabolism Neuroscience

Neuroimaging of hypothalamic mechanisms related to glucose metabolism in anorexia nervosa and obesity

Abstract

BACKGROUND Given the heightened tolerance to self-starvation in anorexia nervosa (AN), 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 participants, and 24 healthy participants with obesity underwent 2 MRI sessions in a single-blind, randomized, case-controlled crossover study. 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. Furthermore, patients with AN displayed blunted reactivity in the nucleus accumbens and amygdala. Compared with the normal-weight participants and control participants with obesity, the patients with AN failed to show functional connectivity between the hypothalamus and the reward-related brain regions during water infusion relative to glucose infusion. Finally, the 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 study provides 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).

Authors

Joe J. Simon, Marion A. Stopyra, Esther Mönning, Sebastian Sailer, Nora Lavandier, Lars P. Kihm, Martin Bendszus, Hubert Preissl, Wolfgang Herzog, Hans-Christoph Friederich

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Figure 5

Differences between groups in BOLD signal response during glucose infusion.

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Differences between groups in BOLD signal response during glucose infusi...
(A) Group differences in hypothalamus reactivity during glucose infusion (comparison between all 3 groups: F2,73 = 5.74, P = 0.005, by repeated-measures ANOVA). (B) Differences between groups in BOLD signal response in the NAcc during glucose infusion (comparison between all 3 groups: F2,73 = 4.32, P = 0.017, by repeated-measures ANOVA; normal-weight controls vs. patients with AN: t50 = 2.12, P = 0.038; normal-weight controls vs. controls with obesity: t50 = 2.57, P = 0.013; and controls with obesity vs. patients with AN: t46 = –0.15, P = 0.882, by Student’s t test). (C) Differences between groups in BOLD signal response in the amygdala during glucose infusion (comparison between all 3 groups: F2,73 = 10.84, P < 0.001). No significant differences were observed between normal-weight controls and patients with AN (t50 = 1.66, P = 0.103), but significant differences were observed between normal-weight controls and controls with obesity (t50 = –4.35, P < 0.001) and between controls with obesity and patients with AN (t46 = –3.59, P < 0.001). In the box-and-whisker plots, the horizontal bar indicate the median, the box edges represent the 25th and 75th percentiles, and the whiskers represent the 10th and 90th percentiles. *P ≤ 0.05, **P ≤ 0.01, and ***P ≤ 0.001, by post hoc 2-sample, 2-tailed Student’s t test.