A third group of differentially expressed metabolic genes in our present study (down-regulation of argininosuccinate synthetase and up-regulation of angiopoietin-like 4) in ZDF hearts is potentially regulated by oxidative and nitrosative stress which is increased in metabolic diseases e.g. hyperlipidemia[13,40,64], hypertension[65], insulin resistance[66], diabetes mellitus[67] and in the heart of ZDF rats as shown in previous[42] as well as in the present study. This evidence concerns the gene ASS1 and metabolic disease.