Neurohormonal Responses to Hunger, Satiation, and Satiety in Normal Weight, Obesity, and Anorexia

Background: Food intake is regulated by homeostatic and hedonic systems that interact in a complex neuro-entero-endocrine network. Dysregulation in energy intake can lead to diseases like obesity (OB) and anorexia nervosa (AN). However, little is known about the neurohormonal response patterns to food intake in normal weight (NW), OB, and AN. Methods: During an ad libitum nutrient drink (Ensure®) test, patients completed three pseudo-continuous arterial spin labeling (pCASL) MRI scans. The first scan was performed before starting the NDT with patients in a >12hr overnight fast (Hunger), the second after reaching maximal fullness (Satiation), and the third 30-min after satiation (Satiety). We measured blood levels of ghrelin, cholecystokinin (CCK), glucagon-like peptide (GLP-1), and peptide YY (PYY) with every MRI scan. Semiquantitative cerebral blood flow (CBF) maps in mL/100 gr brain/min were calculated and normalized (nCBF) with the CBF in the frontoparietal white matter. The hypothalamus, nucleus accumbens [NAc], and dorsal striatum [DS] were selected as regions of interest (ROIs). Results: A total of 53 patients, 7 with AN, 17 with NW (body-mass index [BMI] 18.5-24.9 kg/m2), and 29 with OB (BMI >30 kg/m2) completed the study. The NW group had a progressive decrease in all five ROIs during the three stages of food intake (hunger, satiation, and satiety). In contrast, patients with OB showed a minimal change from hunger to satiety in all five ROIs. The AN group had a sustained nCBF in the hypothalamus and DS, from hunger to satiation, with a quent in nCBF from satiation to satiety. All three groups had similar hormonal response patterns with a decrease in ghrelin, an increase in GLP-1 and PYY, and no change in CCK. Conclusions: Conditions of regulated (NW) and dysregulated (OB and AN) energy balance hold distinctive neurohormonal activity patterns in response to hunger, satiation, and satiety.