QRFP 43 is a RFamide peptide present in the ventromedial nucleus (VMN) and lateral hypothalamus. it stimulates food intake in mice and its chronic infusion induces hyperphagia, reduced thermogenesis, and obesity, in this experiment, we measured it in the VMN and lateral hypothalamus of Long-Evans rats fed either a high-fat (HF), control, or low-fat (LF) diet in parallel with plasma leptin, adiposity, and energy intake. After 8 weeks of ad libitum diet intake, energy intake of HF rats was similar to that of control rats. In the VMN, QRFP 43 was completely undetectable in HF rats and its tissue concentration in control rats was significantly lower than in LF rats (p < 0.03). HF rats had higher levels of leptin than control rats (+24%: p < 0.03) and than LF rats (+42%; p < 0.002). The QRFP 43 concentration in the VMN was inversely correlated with plasma leptin (r = -0.34; P < 0.04) and with the adipogenic index of the diet (p < 0.02) but not with insulin. We conclude that the decrease of the orexigenic drive mediated by QRFP 43 could contribute to the normalization of caloric intake in HF diet fed rats. QRFP 43 might play a role downstream of leptin in the regulation of feeding behavior. (C) 2009 Elsevier Inc. All rights reserved.