Dietary Protein Modifies the Effect of theMC4RGenotype on 2-Year Changes in Appetite and Food Craving: The POUNDS Lost Trial.
Background:The melanocortin-4 receptor (MC4R) plays a pivotal role in the regulation of appetite and eating behavior. Variants in theMC4Rgene have been related to appetite and obesity.Objective:We aimed to examine whether weight-loss diets modified the effect of the "obesity-predisposing"MC4Rgenotype on appetite-related measures in a randomized controlled trial.Methods:A total of 811 overweight and obese subjects [25 ≤ body mass index (BMI; kg/m2) ≤ 40] aged 30-70 y were included in the 2-y POUNDS Lost (Preventing Overweight Using Novel Dietary Strategies) trial. We genotypedMC4Rrs7227255 in 735 overweight adults and assessed appetite-related characteristics, including craving, fullness, hunger, and prospective consumption, as well as a composite appetite score. We examined the effects of the genotype-by-weight-loss diet intervention interaction on appetite variables by using general linear models in both the whole population and in white participants only.Results:We found that dietary protein intake (low compared with high: 15% of energy compared with 25% of energy, respectively) significantly modifiedMC4Rgenetic effects on changes in appetite score and craving (P-interaction = 0.03 and 0.02, respectively) at 2 y, after adjustment for age, sex, ethnicity, baseline BMI, weight change, and baseline perspective phenotype. The obesity-predisposing A allele was associated with a greater increase in overall appetite score (β = 0.10,P= 0.05) and craving (β = 0.13,P= 0.008) compared with the non-A allele among participants who consumed a high-protein diet.MC4Rgenotype did not modify the effects of fat or carbohydrate intakes on appetite measures. Similar interaction patterns were observed in whites.Conclusion:Our data suggest that individuals with theMC4Rrs7227255 A allele rather than the non-A allele might experience greater increases in appetite and food craving when consuming a high-protein weight-loss diet. This trial was registered at clinicaltrials.gov as NCT00072995.
Epidemiology Domain, Saw Swee Hock School of Public Health, and.|Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.|Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA.
Tao
T
Huang
Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA.
Yan
Y
Zheng
Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA.|Nutritional Epidemiology Program, Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA.
Adela
A
Hruby
Pennington Biomedical Research Center of the Louisiana State University System, Baton Rouge, LA.
Donald A
DA
Williamson
Pennington Biomedical Research Center of the Louisiana State University System, Baton Rouge, LA.
George A
GA
Bray
School of Medicine, Tufts University, Boston, MA.
Yiru
Y
Shen
Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA.
Frank M
FM
Sacks
Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA; nhlqi@channing.harvard.edu.|Department of Epidemiology, School of Public Health and Tropical Medicine, Tulane University, New Orleans, LA; and.|Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.
Lu
L
Qi
D000328:Adult; D000368:Aged; D001066:Appetite / Q000187:drug effects / Q000235:genetics*; D066249:Craving / Q000187:drug effects*; D004044:Dietary Proteins / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D005786:Gene Expression Regulation; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009765:Obesity; D044105:Receptor, Melanocortin, Type 4 / Q000235:genetics / Q000378:metabolism*
D004044:Dietary Proteins; C470072:MC4R protein, human; D044105:Receptor, Melanocortin, Type 4
MC4R genotype; appetite; food craving; gene-diet interaction; protein diet; weight-loss trial