Gut-derived appetite regulating hormones across the anorexia nervosa spectrum

Maged Muhammed; Helen Burton-Murray; Franziska Plessow; Kendra R Becker; Lauren Breithaupt; Meghan Lauze; Meghan Slattery; Hang Lee; Jennifer J Thomas; Kamryn T Eddy; Elizabeth A Lawson; Madhusmita Misra

doi:10.1016/j.psyneuen.2024.107257

Gut-derived appetite regulating hormones across the anorexia nervosa spectrum

Psychoneuroendocrinology. 2024 Dec 16:172:107257. doi: 10.1016/j.psyneuen.2024.107257. Online ahead of print.

Authors

Affiliations

¹ Neuroendocrine Unit, Division of Endocrinology, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA; Division of Endocrinology, Diabetes and Hypertension, Brigham and Women's Hospital, Boston, MA, USA; Adult Inpatient Medicine, Department of Medicine, Newton Wellesley Hospital, Newton, MA, USA; Multidisciplinary Eating Disorders Research Collaborative, Mass General Brigham, Boston, MA, USA; Harvard Medical School, Boston, MA, USA.
² Multidisciplinary Eating Disorders Research Collaborative, Mass General Brigham, Boston, MA, USA; Harvard Medical School, Boston, MA, USA; Center for Neurointestinal Health, Division of Gastroenterology, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA; Eating Disorders Clinical and Research Program, Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA.
³ Neuroendocrine Unit, Division of Endocrinology, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA; Multidisciplinary Eating Disorders Research Collaborative, Mass General Brigham, Boston, MA, USA; Harvard Medical School, Boston, MA, USA; Department of Psychiatry and Behavioral Sciences and Weill Institute for Neurosciences, University of California, San Francisco, CA, USA.
⁴ Multidisciplinary Eating Disorders Research Collaborative, Mass General Brigham, Boston, MA, USA; Harvard Medical School, Boston, MA, USA; Eating Disorders Clinical and Research Program, Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA.
⁵ Neuroendocrine Unit, Division of Endocrinology, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA; Multidisciplinary Eating Disorders Research Collaborative, Mass General Brigham, Boston, MA, USA; Eating Disorders Clinical and Research Program, Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA.
⁶ Harvard Medical School, Boston, MA, USA; Massachusetts General Hospital Biostatistics Center, Boston, MA, USA.
⁷ Neuroendocrine Unit, Division of Endocrinology, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA; Multidisciplinary Eating Disorders Research Collaborative, Mass General Brigham, Boston, MA, USA; Harvard Medical School, Boston, MA, USA.
⁸ Neuroendocrine Unit, Division of Endocrinology, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA; Multidisciplinary Eating Disorders Research Collaborative, Mass General Brigham, Boston, MA, USA; Harvard Medical School, Boston, MA, USA; Division of Pediatric Endocrinology, Department of Pediatrics, University of Virginia, Charlottesville, VA, USA. Electronic address: [email protected].

PMID: 39740360
DOI: 10.1016/j.psyneuen.2024.107257

Abstract

Background: Appetite-regulating hormones are implicated in anorexia nervosa (AN) pathophysiology, however, data are limited for appetite-regulating hormones across the AN weight spectrum. We aimed to investigate fasting and post-prandial concentrations of appetite-regulating hormones - peptide YY (PYY), cholecystokinin (CCK), and ghrelin - among adolescent and young adult females across the AN weight spectrum, specifically those with AN and Atypical AN, and healthy controls (HC).

Methods: Participants (N = 95; ages 11-22 years) included 33 with AN, 25 with Atypical AN, and 37 HC. AN was differentiated from Atypical AN by BMI < 10th percentile for age and sex (if <18 years) or < 18.5 kg/m²(if ≥18 years). Blood samples were collected fasting and 30, 60 and 120 minutes following a standardized meal to assess total PYY, CCK, and total ghrelin concentrations.

Results: Median fasting and post-prandial PYY concentrations were significantly higher in AN vs. HC with medium differences (p = .001-.006, r = .34-.43). Atypical AN had significantly higher PYY concentrations compared to HC at T-0 (p = .027, r = .29) only, and did not significantly differ from concentrations in AN (p = .105-.413, r = .11-.22). Area under the curve (AUC; p = .001; r = .41) and peak PYY concentrations (p = .003; r = .41) were also significantly higher in AN vs. HC with medium differences. There were no significant differences in fasting (p = .885) or post-prandial (p = .846-.993) CCK concentrations across groups. AN and Atypical AN each had significantly higher ghrelin concentrations than HC with small to medium effect (AN vs HC p = .004-.025, r = .27-.36; Atypical AN vs HC p = .004-.033; r = .28-.28).

Conclusions: Higher peak postprandial concentrations of anorexigenic PYY in AN (compared to HC) may facilitate dietary restriction and contribute to maintenance of lower weight. Lack of CCK suppression in AN is maladaptive in the context of undernutrition. Despite continued restriction, ghrelin is adaptively higher in AN overall and may not be differentiated by weight status.

Keywords: Anorexia nervosa; Cholecystokinin; Eating disorder; Ghrelin; Peptide YY.