By comparing lean PPARγ wt animals on a chow diet with obese littermates receiving a high fat diet, normally fed PPARγ DN and PPARγ DN mice with diet-induced obesity, we were able to differentiate effects only induced by diet from those effects observed as a consequence of reduced PPARγ activity and effects due to an interaction between diet and genotype. The gene discussed is PPARG; the disease is obesity due to melanocortin 4 receptor deficiency.