The anorectic effects of alpha-lipoicacid are mediated by central AMPK and are not due to taste aversion in chicken (Gallus gallus)

• We provided dietary α-lipoic-acid, a central AMPK inhibitor in mammals, to broiler chicks for 7 days.
• Dietary α-lipoic-acid decreased feed intake of broiler chicks.
• The anorectic effect was not due to taste aversion.
• The anorectic effect was due to the reduced hypothalamic phosphorylated AMPKα (decreased mRNA and protein levels).
• We observed a physiological counteractive feedback via altered (an)orexigenic hypothalamic neuropeptides.

AMP-activated protein kinase (AMPK) is an evolutionary conserved cellular energy sensor, which plays a pivotal role in mammalian energy homeostasis. The present study was aimed to explore the possible involvement of hypothalamic AMPK in feed intake regulation of broiler chickens. Hence, diets with 0, 0.05% or 0.1% α-lipoicacid (α-LA), a known AMPK inhibitor in mammals, were provided to broiler chicks for 7 days. Alpha-LA exerted an anorectic effect, and the conditioned taste aversion test demonstrated that the effect was due to the alteration in satiety and not taste effects. However, the curtailed feed intake induced by α-LA disappeared on day 7. Hypothalamic AMPKα1 mRNA levels were significantly decreased by the dietary α-LA in concert with the reduced abundance in total AMPKα protein. The phosphorylated AMPKα was also decreased to a similar extend, resulting in an unaltered phosphorylated AMPKα/total AMPKα ratio. In addition, hypothalamic corticotropin releasing hormone mRNA levels were enhanced by α-LA. Interestingly, the mRNA expressions of hypothalamic orexigenic agouti-related peptide and neuropeptide Y were up-regulated, while the anorexigenic proopiomelanocortin and its transcription regulator hypoxia-inducible factor-1α were down-regulated, probably as a physiological reaction in order to counteract the altered energy balance.In conclusion, dietary α-LA decreased feed intake of broiler chicks. The anorectic effect was due to the reduced hypothalamic phosphorylated AMPKα as reflected in its decreased mRNA and protein levels. However, the anorectic effect of α-LA was progressively diminished after 7 days of treatment, likely by a physiological counteractive feedback via changing neuropeptides involved in energy balance regulation.