Recent studies have indicated that long chain fatty acids, or their metabolic intermediates acyl-CoAs, act as signals of body's energy state and influence the hypothalamic regulation of food intake. In cytosol Acyl-CoAs are bound by proteins such as acyl-CoA binding protein (ACBP). This is influencing the metabolic and regulatory functions of acyl-CoAs. We utilized transgenic (tg) rats overexpressing mouse ACBP gene to study the role of ACBP on the hypothalamic regulation of food intake. Overexpression of ACBP had no influence on the food intake or the body weight of rats. Furthermore, ACBP overexpression did not affect brain acyl-CoA pool. In contrast, tg rats had nutritional state specific changes in the gene expression profile. In fed tg rats FAS, SIRT-1 and PPARd mRNA levels were reduced 28%, 26 % and 43 %, respectively, while the mRNA level of CPT Ic was increased by 22 %. mRNA levels of SREBP-1 and protein levels of AMPKa were equal between fed tg and syngenic animals. Our results demonstrate that preventive measures abolish the effects of the constant overexpression of ACBP. These include the observed changes in the gene expression that prevent the increase of acyl-CoA pool size.