Under the hypothesis of
obesity as a polygenetic disease numerous genes have been associated with an obese phenotype and metabolic co-morbidities. The
cannabinoid receptor 1 (CB 1) is part of an underinvestigated system that participates in appetite control. Previous publications suggest that the
endocannabinoid systems interact with the better understood
leptin-
melanocortin axis.
Neuropeptide Y (NPY) is a player in the latter. Finally
resistin has been shown to influence NPY expression in the brain. In a cohort of 1721 caucasion men and women with a BMI of 25kg/m(2) or more we therefore investigated three candidate polymorphisms at baseline and following 3 months low fat
caloric restriction diet by polymerase chain reaction and restriction digestion: the 1359 G/A variant of the
cannabinoid receptor 1 (CB1), the L7P variation in
neuropeptide Y (NPY) and the -420C>G polymorphism in
resistin. Comparing groups according to genotype for each gene separately revealed significant results at baseline only for the CB1 gene. However, upon dieting significant data was found for all 3 genes. Carriers of at least one A allele in CB1 lost more weight and reduced
LDL cholesterol more than wildtype patients. LL homocygotes in NPY had a greater reduction in
glucose,
triglycerides, and
LDL cholesterol whereas in
resistin carriers of the G allele had a greater reduction in weight and
triglycerides. Creating two groups defined by NPY and
resistin genotype, respectively, with similar BMI values resulted in significant differences concerning
weight loss and metabolic improvement. In conclusion, genetic polymorphisms associated with
obesity may become relevant only under the condition of a low calory diet. The presence of a certain genotype may then be beneficial for
obesity treatment.