Charumathi Baskaran, Kamryn T Eddy, Karen K Miller, Erinne Meenaghan, Madhusmita Misra and Elizabeth A Lawson
Leptin secretory dynamics across the weight spectrum and their relationship with disordered eating psychopathology have not been studied. Our objective was to compare leptin secretory dynamics in 13 anorexia nervosa (AN), 12 overweight/obese (OB) and 12 normal-weight women using deconvolution analysis.
In this cross-sectional study conducted at a tertiary referral center, serum leptin levels were obtained every 20 min from 2000 to 0800 h. Dual energy X-ray absorptiometry was used to measure percent body fat. Disordered eating psychopathology was assessed by the Eating Disorders Examination-Questionnaire (EDE-Q) and the Eating Disorders Inventory-2 (EDI-2).
The groups differed for basal leptin secretion (BASAL) (P=0.02). Mean leptin pulse amplitude, pulse mass, total pulsatile secretion (TPS) and area under the curve (AUC) were significantly different between groups before and after adjustment for BASAL (P<0.0001 for all). Leptin AUC correlated strongly with TPS (r=0.97, P<0.0001) and less with BASAL (r=0.35, P=0.03). On multivariate analysis, only TPS was a significant predictor of leptin AUC (P<0.0001). TPS was inversely associated with most EDE-Q and EDI-2 parameters and the associations remained significant for EDE-Q eating concern (P=0.01), and EDI-2 asceticism, ineffectiveness and social insecurity (P<0.05) after adjusting for BASAL. These relationships were not significant when controlled for percent body fat.
Secretory dynamics of leptin differ across weight spectrum, with mean pulse amplitude, mean pulse mass and TPS being low in AN and high in OB. Pulsatile, rather than basal secretion, is the major contributor to leptin AUC. Decreased pulsatile leptin is associated with disordered eating psychopathology, possibly reflecting low percent body fat in AN.
Elizabeth A Lawson, Laura M Holsen, Rebecca DeSanti, McKale Santin, Erinne Meenaghan, David B Herzog, Jill M Goldstein and Anne Klibanski
Corticotrophin-releasing hormone (CRH)-mediated hypercortisolemia has been demonstrated in anorexia nervosa (AN), a psychiatric disorder characterized by food restriction despite low body weight. While CRH is anorexigenic, downstream cortisol stimulates hunger. Using a food-related functional magnetic resonance imaging (fMRI) paradigm, we have demonstrated hypoactivation of brain regions involved in food motivation in women with AN, even after weight recovery. The relationship between hypothalamic–pituitary–adrenal (HPA) axis dysregulation and appetite and the association with food-motivation neurocircuitry hypoactivation are unknown in AN. We investigated the relationship between HPA activity, appetite, and food-motivation neurocircuitry hypoactivation in AN.
Cross-sectional study of 36 women (13 AN, ten weight-recovered AN (ANWR), and 13 healthy controls (HC)).
Peripheral cortisol and ACTH levels were measured in a fasting state and 30, 60, and 120 min after a standardized mixed meal. The visual analog scale was used to assess homeostatic and hedonic appetite. fMRI was performed during visual processing of food and non-food stimuli to measure the brain activation pre- and post-meal.
In each group, serum cortisol levels decreased following the meal. Mean fasting, 120 min post-meal, and nadir cortisol levels were high in AN vs HC. Mean postprandial ACTH levels were high in ANWR compared with HC and AN subjects. Cortisol levels were associated with lower fasting homeostatic and hedonic appetite, independent of BMI and depressive symptoms. Cortisol levels were also associated with between-group variance in activation in the food-motivation brain regions (e.g. hypothalamus, amygdala, hippocampus, orbitofrontal cortex, and insula).
HPA activation may contribute to the maintenance of AN by the suppression of appetitive drive.
Elizabeth A Lawson, Kamryn T Eddy, Daniel Donoho, Madhusmita Misra, Karen K Miller, Erinne Meenaghan, Janet Lydecker, David Herzog and Anne Klibanski
Disordered eating occurs in women at both weight extremes of anorexia nervosa (AN) and obesity. Cortisol, peptide YY (PYY), leptin, and ghrelin are hormones involved in appetite and feeding behavior that vary with weight and body fat. Abnormal levels of these hormones have been reported in women with AN, functional hypothalamic amenorrhea (HA), and obesity. The relationship between appetite-regulating hormones and disordered eating psychopathology is unknown. We therefore studied the relationship between orexigenic and anorexigenic hormones and disordered eating psychopathology in women across a range of weights.
A cross-sectional study of 65 women, 18–45 years: 16 with AN, 12 normal-weight with HA, 17 overweight or obese, and 20 normal-weight in good health.
Two validated measures of disordered eating psychopathology, the Eating Disorders Examination-Questionnaire (EDE-Q) and Eating Disorders Inventory-2 (EDI-2), were administered. Fasting PYY, leptin, and ghrelin levels were measured; cortisol levels were pooled from serum samples obtained every 20 min from 2000 to 0800 h.
Cortisol and PYY levels were positively associated with disordered eating psychopathology including restraint, eating concerns, and body image disturbance, independent of body mass index (BMI). Although leptin levels were negatively associated with disordered eating psychopathology, these relationships were not significant after controlling for BMI. Ghrelin levels were generally not associated with EDE-Q or EDI-2 scores.
Higher levels of cortisol and PYY are associated with disordered eating psychopathology independent of BMI in women across the weight spectrum, suggesting that abnormalities in appetite regulation may be associated with specific eating disorder pathologies.