Delayed gastric emptying observed in adults with severe obesity due to MC4R deficiency
Adults with severe obesity due to a melanocortin‐4 receptor deficiency have a longer gastric emptying time and lower peptide YY levels compared with age- and BMI-matched controls, according to study data.
“By studying people with melanocortin‐4 receptor (MC4R) deficiency, we have shown that MC4R signaling modulates gastric emptying and peptide YY secretion in humans,” Sadaf Farooqi, MBChB (Hons), PhD, FRCP, FMedSci, DSc, a Wellcome Trust principal research fellow and professor of metabolism and medicine at the University of Cambridge, U.K., and colleagues wrote in a study published in Clinical Endocrinology. “Understanding how melanocortin circuits in the brain detect and respond to gut‐derived neural and hormonal signals may provide further insights into the regulation of meal-induced satiety.”
Researchers recruited nine adults with severe obesity and MC4R deficiency from the Genetics of Obesity Study to participate in the study. The participants were matched by 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 the two egg whites as part of a meal after a 6-hour fasting period. Anterior and posterior gut imaging was conducted in 15-minute intervals during the first 2 hours after the meal and at 30-minute intervals for the next 90 minutes. Peptide YY concentrations were measured during a separate 12-hour sampling period in which three meals were eaten 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 analogue scales were used to assess hunger and fullness.
After consuming identical meals, adults with a MC4R deficiency had a longer 10% emptying time (9.3 minutes vs. 5.6 minutes; P = .03), 50% emptying time (61.2 minutes vs. 36.8 minutes; P = .03) and 90% emptying time (203.2 minutes vs. 122.4 minutes; P = .03) compared with controls. The percentage of retention at the end of the test was higher in MC4R group compared with controls (9.7% vs. 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 peptide YY analysis. Those with MC4R deficiency had lower fasting peptide YY (9 pmol/L vs. 16.9 pmol/L; P = .015) and average peptide YY (15.1 pmol/L vs. 21.4 pmol/L; P = .00002) compared with controls. There was no difference in 30- or 60-minute postprandial peptide YY secretion, area under the curve, intermeal peak and visual analogue scales for hunger and fullness between the two groups.
“We found lower fasting and mean peptide YY levels throughout the day without a change in peak postprandial peptide YY secretion,” the researchers wrote. “MC4R signaling may affect basal peptide YY secretory tone, but does not appear to influence the nutrient stimulated postprandial increase in peptide YY, although we acknowledge that these findings are preliminary and larger studies in normal weight, obese and MC4R‐deficient people are needed.”
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