Central administration of corticotropin-releasing factor induces thermogenesis by changes in mitochondrial bioenergetics in neonatal chicks

Corticotropin-releasing factor (CRF), has multiple biological effects and plays a central regulatory role in the hypothalamic-pituitary-adrenal (HPA) axis regulating energy homeostasis that is required for adaptive responses to maintain and support life. Central administration of CRF increases O₂ consumption, CO₂ and heat production resulting in hyperthermia. To determine the precise mechanism for this condition, here we investigated transcripts of candidate genes for thermogenesis and their up-regulator (avian uncoupling protein (avUCP), avian adenine nucleotide translocator (avANT) and avian peroxisome-proliferator-activated receptor-γ co-activator-1α) and mitochondrial bioenergetics (gene transcripts for mitochondrial fatty acid (FA) transport and oxidation enzymes; carnitine-palmitoyl-transferase (CPT)-I; CPT-II, long-chain acyl CoA dehydrogenase (LCAD), 3-hydroxyacyl CoA dehydrogenase (3HADH) and citrate synthase (CS), and enzyme activities of 3HADH and CS) that might explain the bioenergetic basis of CRF-induced increased thermogenesis. Neonatal chicks (Gallus gallus) with and without i.c.v. injection of CRF (42 pmol) were kept at thermoneutral temperature (30 °C) for 3 h. Central administration of CRF increased the core temperature and plasma NEFA level of chicks compared with the control. This CRF-induced increased thermogenesis was not accompanied by enhancement of avUCP and/or avANT gene transcripts and was associated with increased FA oxidation in tissue specific manner: increase in gene transcript levels of CPT-I, CPT-II, LCAD, 3HADH and CS, and increase in enzyme activities of 3HADH and CS were observed in liver and heart while no such changes were observed in skeletal muscle. In conclusion, these results suggest that CRF-induced increased thermogenesis in neonatal chicks was not accompanied by enhancement of gene transcripts of mitochondrial putative thermogenic proteins, and was induced by tissue specific increase in mitochondrial FA transport and β-oxidation enzymes.