Beschreibung:
<jats:title>Abstract</jats:title><jats:p><jats:italic>Objective</jats:italic>: The melanocortin‐4 receptor (<jats:italic>MC4R</jats:italic>) regulates energy intake. On the basis of animal studies, it may also regulate energy expenditure.</jats:p><jats:p><jats:italic>Research Methods and Procedures</jats:italic>: The effect of the Val103Ile polymorphism of the <jats:italic>MC4R</jats:italic> gene on energy metabolism was studied in 229 middle‐aged nondiabetic subjects (Group 1, age 51.2 ± 9.8 years, BMI 26.8 ± 4.5 kg/m<jats:sup>2</jats:sup>) and on weight gain in 1013 elderly subjects (Group 2, age 69.9 ± 2.9 years, BMI 27.4 ± 4.1 kg/m<jats:sup>2</jats:sup>) during a 3.5‐year follow‐up study. In Group 1, insulin sensitivity, energy expenditure, and substrate oxidation were measured with the hyperinsulinemic euglycemic clamp combined with indirect calorimetry.</jats:p><jats:p><jats:italic>Results</jats:italic>: In Group 1, the <jats:italic>Val103Ile</jats:italic> genotype was associated with high rates of energy expenditure (63.42 ± 13.40 in eight subjects with the <jats:italic>Val103Ile</jats:italic> genotype vs. 59.86 ± 7.33 J/kg per minute in 221 subjects with the <jats:italic>Val103Val</jats:italic> genotype, <jats:italic>p</jats:italic> = 0.007), high rates of glucose oxidation (8.90 ± 6.15 vs. 6.07 ± 4.38 μmol/kg per minute, <jats:italic>p</jats:italic> = 0.020), and low levels of free fatty acids (0.45 ± 0.18 vs. 0.56 ± 0.23 mM, <jats:italic>p</jats:italic> = 0.029) in the fasting state, and with high rates of glucose oxidation during the clamp (18.88 ± 4.63 vs. 17.60 ± 3.24 μmol/kg per minute, <jats:italic>p</jats:italic> = 0.031). In Group 2, the <jats:italic>103Ile</jats:italic> allele was associated with an increase in weight gain during the follow‐up (0.78 ± 3.98 vs. −0.82 ± 3.98 kg, <jats:italic>p</jats:italic> = 0.038).</jats:p><jats:p><jats:italic>Discussion</jats:italic>: The Val103Ile polymorphism of the <jats:italic>MC4R</jats:italic> gene is associated with energy expenditure in humans. Furthermore, it may associate with glucose oxidation, free fatty acid levels, and weight gain.</jats:p>