Delayed gastric emptying observed in adults with severe obesity due to MC4R deficiency

January 18, 2022

2 minute read


Disclosures: The authors report no relevant financial information.

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According to the study data, adults with severe obesity due to melanocortin-4 receptor deficiency have longer gastric emptying time and lower YY peptide levels than age-matched controls. age and BMI.

“Studying individuals with melanocortin-4 receptor (MC4R) deficiency, we have shown that MC4R signaling modulates gastric emptying and YY peptide secretion in humans,” Sadaf Farouqi, MBChB (Hons), PhD, FRCP, FMedSci, DSc, Wellcome Trust Principal Investigator and Professor of Metabolism and Medicine at the University of Cambridge, UK, and colleagues wrote in a study published in Clinical endocrinology. “Understanding how melanocortin circuitry in the brain senses and responds to gut-derived neural and hormonal signals may provide additional insight into the regulation of meal-induced satiety.”

Gastric emptying time after meals is longer in adults with severe obesity and MC4R deficiency.
Adults with severe obesity due to MC4R deficiency has longer gastric emptying than controls. Data are from Seelig E, et al. Clin Endocrinol. 2021;doi:10.1111/cen.14615.

Researchers recruited nine adults with severe obesity and MC4R deficit of the study on the genetics of obesity to participate in the study. Participants were matched on age, sex and BMI with a control group with a normal MC4R genotype. To measure gastric emptying, technetium‐99m tin colloid was added to two egg whites. Participants ate both egg whites as part of a meal after a 6-hour fasting period. Anterior and posterior intestinal imaging was performed at 15-minute intervals for the first 2 hours after the meal and at 30-minute intervals for the next 90 minutes. YY peptide concentrations were measured during a separate 12-hour sampling period during which three meals were consumed at 8 a.m., noon, and 5:30 p.m. Blood was drawn every 30 minutes from 7:30 a.m. to 8:30 p.m. and visual analog scales were used to assess hunger and satiety.

After consuming identical meals, adults with MC4R deficiency had a 10% longer emptying time (9.3 minutes versus 5.6 minutes; P = 0.03), 50% emptying time (61.2 minutes versus 36.8 minutes; P = 0.03) and 90% emptying time (203.2 minutes versus 122.4 minutes; P = 0.03) compared to controls. The percentage of retention at the end of the test was higher in the MC4R group compared to the controls (9.7% versus 2.1%; P = .02).

There were six adults with MC4R deficiency (mean age, 31.7 years) and five controls (mean age, 55 years) included in the YY peptide analysis. Those with MC4R deficiency had lower fasting peptide YY (9 pmol/L versus 16.9 pmol/L; P = 0.015) and the average YY peptide (15.1 pmol/L versus 21.4 pmol/L; P = 0.00002) compared to controls. There was no difference in postprandial secretion of peptide YY at 30 or 60 minutes, area under the curve, interprandial peak, and visual analog scales for hunger and fullness between the two groups.

“We found lower fasting and mean Peptide YY levels throughout the day with no change in peak postprandial Peptide YY secretion,” the researchers wrote. “MC4R signaling may affect the basal secretory tone of peptide YY, but does not appear to influence the nutrient-stimulated postprandial increase in peptide YY, although we recognize that these results are preliminary and that larger studies in people with normal weight, obese and deficient in MC4R are required. ”

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