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.

Estradiol and appetite: To eat or not to eat

“…Thus, it is possible that the lack of circulating E2 could impair refeeding responses in these subjects. In line with this, recent data have reported that blunted hypothalamic glucose reactivity might be related to the pathophysiology of AN [ 8 ]. Whether that effect may be related to depleted E2 levels would require further investigation.…”

A Systematic Review and Meta-Analysis Finds Increased Blood Levels of All Forms of Ghrelin in Both Restricting and Binge-Eating/Purging Subtypes of Anorexia Nervosa

“…Heterogeneity among studies was high (Ƭ 2 = 2.35, I 2 = 94.16%). The same pattern of results emerged for acyl ghrelin SMD acyl = 2.02, CI acyl = [1.14, 2.89], p < 0.001 (based on data of 13 studies [ 23 , 44 , 47 , 49 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 ] and effect sizes, including 191 AN patients, and 185 HC individuals as well as data points), see Figure 3 . Again, heterogeneity of the pooled estimate was high (Ƭ 2 = 1.26, I 2 = 85.77%).…”

Backstage of Eating Disorder—About the Biological Mechanisms behind the Symptoms of Anorexia Nervosa

“…However, patients with anorexia nervosa do not adequately respond to homeostatic body signals that should stimulate weight restoration. The investigation of in vivo hypothalamic responses to nutrient ingestion showed a reduced reactivity upon glucose administration (i.e., a decreased activity of the hypothalamus following glucose infusion was not observed) [54,55]. The same study reported impaired functional connectivity between the hypothalamus and mesocorticolimbic reward system.…”