Effect of high dietary copper on the expression of hypothalamic appetite regulators in weanling pigs

It is well recognized that high dietary copper (Cu) promotes growth performance in pigs. In addition, dietary Cu supplementation has shown to be associated with improved feed intake. Cu could be transported through the blood-brain barrier as a free Cu ion and participates in regulation of neuroendocrine action in the brain. For these reasons, the objective of the current study was to evaluate the effect of Cu supplementation, at a rate of 100, 175 or 250 mg/kg feed, on feed intake and expression of hypothalamic appetite-regulating genes such as orexin, type 2 orexin receptor (OrexinR2), proopiomelanocortin (POMC), melanocortin-4 receptor (MC4R), long-form leptin receptor (LeptinRb), and hypothalamic AMP-activated protein kinase α2 subunit (AMPKα2) in weanling pigs by sensitive and quantitative real time-polymerase chain reaction (real time-PCR) method. One hundred crossbred pigs were assigned to four groups of 25 pigs, each comprising five replicates of 5 animals. Groups were then randomly assigned to treatments consisted of treatment 1 (control; 10 mg/kg CuSO₄), 2 (100 mg/kg CuSO₄), 3 (175 mg/kg CuSO4), and 4 (250 mg/kg CuSO₄). On d 21 of the experiment 5 pigs from each group were slaughtered and the hypothalamuses were collected for determination of appetite-regulating genes mRNA expression level.

The results showed that average daily feed intake and average daily gain were higher (P<0.05) in 250 and 175, 250 mg/kg Cu supplemented groups, respectively, than in the 10 mg/kg group. Feed:gain ratio was lower in pigs fed the diets with 250 mg/kg Cu (P<0.05) than in the 10 mg/kg group. Furthermore, the abundances of neuropeptide Y (NPY) mRNA in hypothalamus were higher in 250 mg/kg Cu supplemented groups (P<0.05), whereas the abundances of POMC and LeptinRb mRNA were significantly reduced (P<0.05) in 170, 250 mg/kg and 100, 175, 250 mg/kg Cu supplemented groups, respectively. No difference was found for AMPKα2, MC4R, orexin, OrexinR2 mRNA expression (P>0.05).

In summary, supplementing diets with 250 mg/kg Cu stimulates feed intake and results in an enhancement in weanling pigs’ growth. Furthermore, the shifted hypothalamic appetite-regulating genes expression profile suggests that down-regulation of LeptinRb mRNA expression might contribute to the stimulation of feeding of high dietary Cu supplementation via regulation of NPY and POMC mRNA expression.