The aim of the study was to describe the effects of acetate on hypothalamic G-protein-coupled receptor (GPR) 41 or 43, 5’-AMP-activated protein kinase (AMPK) signalling, mitogen-activated protein kinases (MAPKs) signalling and (an)orexigenic neuropeptides. Forty rabbits (Hyla, 35-day old) were randomly assigned to one of two treatment groups: intravenous injection of acetate (0.5 mg · kg−1 body weight) or vehicle (control). The acetate treatment decreased the rabbit feed intake within 5 h as compared with the control (P < 0.05). Although the acetate treatment had no effect on hypothalamic neuropeptide Y, agouti-related protein, cocaine-amphetamine-regulated transcript, GPR41, acetyl-CoA carboxylase, fatty acid synthase and carnitine palmitoyltransferase-1 mRNA levels (P > 0.05), it significantly increased the gene expression of the pro-opiomelanocortin (POMC) and GPR43 (P < 0.05). Moreover, intravenous injection of acetate did not affect the protein levels of phosphorylated extracellular signal-regulated kinases, AMPK or p38 MAPK in comparison with the control group (P > 0.05); however, there was a significant increase in GPR43 protein level and decrease in phosphorylated c-Jun N-terminal kinases (JNK) level (P < 0.05). So, acetate induced anorexia via the up-regulation of hypothalamic POMC gene expression, which may be associated with membrane GPR43 and intracellular JNK signalling.