. 2025 Feb:172:107257.

doi: 10.1016/j.psyneuen.2024.107257. Epub 2024 Dec 16.

Gut-derived appetite regulating hormones across the anorexia nervosa spectrum

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; Division of Pediatric Endocrinology, Massachusetts General Hospital, Boston, MA, USA. Electronic address: abp6bd@uvahealth.org.

PMID: 39740360
PMCID: PMC11830529 (available on 2026-02-01)
DOI: 10.1016/j.psyneuen.2024.107257

Gut-derived appetite regulating hormones across the anorexia nervosa spectrum

Maged Muhammed et al. Psychoneuroendocrinology. 2025 Feb.

. 2025 Feb:172:107257.

doi: 10.1016/j.psyneuen.2024.107257. Epub 2024 Dec 16.

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; Division of Pediatric Endocrinology, Massachusetts General Hospital, Boston, MA, USA. Electronic address: abp6bd@uvahealth.org.

PMID: 39740360
PMCID: PMC11830529 (available on 2026-02-01)
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.

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Conflict of interest statement

Declaration of Competing Interest The authors declare the following financial interests/personal relationships Dr. Lawson receives grant support and research study drug from Tonix Pharmaceuticals. Dr. Lawson and/or immediate family member holds stock in Thermo Fisher Scientific, Zoetis, Danaher Corporation, Intuitive Surgical, Merck and West Pharmaceutical Services. Dr. Lawson is an inventor on US provisional patent application no. 63/467,980 (Oxytocin-based therapeutics to improve cognitive control in individuals with attention deficit hyperactivity disorder). Dr. Misra has consulted for Regeneron and Kyss Pharmaceuticals, receives study drug donation from Tonix Pharmaceuticals. Drs. Lawson and Misra receive royalties from UpToDate. Dr. Breithaupt is a consultant and on the scientific advisory board for Otsuka Pharma. Drs. Eddy and Thomas receive royalties from Cambridge University Press for the sale of their book, Cognitive-Behavioral Therapy for Avoidant/Restrictive Food Intake Disorder: Children, Adolescents, and Adults. Drs. Eddy and Thomas receive consulting fees from Equip Health. Dr. Becker, Dr. Eddy and Dr. Thomas receive royalties from Cambridge University Press for their book The Picky Eater’s Recovery Book: Overcoming Avoidant/Restrictive Food Intake Disorder. Drs. Burton-Murray and Thomas receive royalties from Oxford University Press for the sale of their book Cognitive-Behavioral Therapy for Rumination Syndrome. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

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References

1. APA, 2022. Diagnostic And Statistical Manual Of Mental Disorders, Fifth Edition, Text Revision (DSM-5-TR). American Psychiatric Association. 10.1176/appi.books.9780890425787. - DOI
1. Ariyasu H, Takaya K, Tagami T, Ogawa Y, Hosoda K, Akamizu T, Suda M, Koh T, Natsui K, Toyooka S, Shirakami G, Usui T, Shimatsu A, Doi K, Hosoda H, Kojima M, Kangawa K, Nakao K, 2001. Stomach is a major source of circulating ghrelin, and feeding state determines plasma ghrelin-like immunoreactivity levels in humans. J Clin Endocrinol Metab 86, 4753–4758. - PubMed
1. Atalayer D, Gibson C, Konopacka A, Geliebter A, 2013. Ghrelin and eating disorders. Prog Neuropsychopharmacol Biol Psychiatry 40, 70–82. - PMC - PubMed
1. Batterham RL, Bloom SR, 2003. The gut hormone peptide YY regulates appetite. Ann N Y Acad Sci 994, 162–168. - PubMed
1. Becker KR, Mancuso C, Dreier MJ, Asanza E, Breithaupt L, Slattery M, Plessow F, Micali N, Thomas JJ, Eddy KT, Misra M, Lawson EA, 2021. Ghrelin and PYY in low-weight females with avoidant/restrictive food intake disorder compared to anorexia nervosa and healthy controls. Psychoneuroendocrinology 129, 105243. - PMC - PubMed

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Gut-derived appetite regulating hormones across the anorexia nervosa spectrum

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Gut-derived appetite regulating hormones across the anorexia nervosa spectrum

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