1. Obesity due to melanocortin 4 receptor (MC4R) deficiency is associated with delayed gastric emptying
- Author
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I. Sadaf Farooqi, Eleonora Seelig, Evelyn Shin, John R. Buscombe, Agatha A. van der Klaauw, Julia M. Keogh, Daniel Gillett, Elana Henning, Gillett, Daniel [0000-0002-9773-6502], van der Klaauw, Agatha A [0000-0001-6971-8828], Farooqi, I Sadaf [0000-0001-7609-3504], and Apollo - University of Cambridge Repository
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medicine.medical_specialty ,obesity ,Gastroparesis ,Endocrinology, Diabetes and Metabolism ,Enteroendocrine cell ,MC4R ,Endocrinology ,gastric emptying ,Internal medicine ,medicine ,Humans ,Peptide YY ,Meal ,Gastric emptying ,PYY ,business.industry ,digestive, oral, and skin physiology ,Area under the curve ,medicine.disease ,Postprandial Period ,Obesity ,Melanocortin 4 receptor ,Postprandial ,Receptor, Melanocortin, Type 4 ,business ,hormones, hormone substitutes, and hormone antagonists ,Hormone - Abstract
Objective People who are severely obese due to melanocortin-4 receptor (MC4R) deficiency experience hyperphagia and impaired fullness after a meal (satiety). Meal-induced satiety is influenced by hormones, such as peptide-YY (PYY), which are released by enteroendocrine cells upon nutrient delivery to the small intestine. Design We investigated whether gastric emptying and PYY levels are altered in MC4R deficiency. Methods Gastric emptying was measured with a gastric scintigraphy protocol using technetium-99m (99 Tcm )-Tin Colloid for 3.5 h in individuals with loss of function MC4R variants and a control group of similar age and weight. In a separate study, we measured plasma PYY levels before and at multiple time points after three standardised meals given to individuals with MC4R deficiency and controls. Fasting PYY (basal secretion) and postprandial PYY levels were measured and the area under the curve and inter-meal peak were calculated. Results We found that gastric emptying time was significantly delayed and percentage meal retention increased in individuals with MC4R deficiency compared to obese controls. In addition, fasting and mean PYY secretion throughout the day were decreased in MC4R deficiency, whereas postprandial PYY secretion was unaltered. Conclusion Delayed gastric emptying and reduced basal PYY secretion may contribute to impaired satiety in people with obesity due to MC4R deficiency.
- Published
- 2021
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