AMP-activated protein kinase controls metabolism and heat production during embryonic development in birds

Abstract

SUMMARYDuring embryonic and early juvenile development, endotherms must balance energy allocation between growth and heat production. Failure to either match the ATP demand of growing tissue or produce heat at the correct developmental stage will lead to damage of the organism. We tested the hypothesis that AMP-activated protein kinase (AMPK) is involved in the regulation of energy metabolism and heat production during development in the chicken (Gallus gallus). We show that mRNA concentrations of regulatory and catalytic AMPK subunits, AMPK total protein, and AMPK phosphorylation increase during development [3days (-3days) and one day (-1day) before hatching, and +1day and +8days after hatching] in liver, and to a lesser extent in skeletal muscle. Chronic stimulation with 5-aminoimidazole-4-carboxamide-1--D-ribofuranoside (AICAR) significantly increases AMPK phosphorylation in skeletal muscle and in liver. This increase was paralleled by significant increases in heat production, glucose utilization, and liver and skeletal muscle mitochondrial capacity (citrate synthase activity). The effects of AMPK are likely to be mediated by inhibition of acetyl CoA carboxylase (ACC) after hatching, when ACC protein concentration increases significantly, and by a significant AMPK-induced increase in PGC-1 mRNA concentration (at +1day), but not in NRF-1 mRNA concentration. AMPK phosphorylation is under the control of thyroid hormone, and AMPK phosphorylation decreases significantly following the induction of hypothyroidism. We propose AMPK as a principal regulatory mechanism during the transition from ectothermy to endothermy in birds, and show that AMPK function in birds is similar to that observed in mammals.

Thermal Manipulation during Embryogenesis Has Long-Term Effects on Muscle and Liver Metabolism in Fast-Growing Chickens

“…Indeed, in the present study, we found an increase in AMPK phosphorylation in TMCh chickens as compared to all other groups. AMPK has been shown to trigger skeletal muscle glucose utilization in chicken embryos [41]. In mammals activation of AMPK induces the membrane translocation of the GLUT transporter in skeletal muscle [42].…”

Early Expression of Hypocretin/Orexin in the Chick Embryo Brain

“…In birds, heat production starts prenatally, and is essential for the transition from ectothermy to endothermy [78]. Heat is generated through non-shivering thermogenesis in muscle and liver (birds do not have brown adipose tissue) and is controlled by thyroid hormones [78].…”

Thermal conditions experienced during differentiation affect metabolic and contractile phenotypes of mouse myotubes

“…All antibodies were from Abcam (Cambridge, MA), and we determined concentrations of total fast (ab51263) and slow (ab11083) skeletal MHCs, thyroid receptor 1 ϩ 2 (ab42565), AMPK ␣1 ϩ ␣2 (ab80039), phosphorylated AMPK ␣1 (phosphorylated at T173) and ␣2 (phosphorylated at T172; ab133448), and ␣-tubulin (ab80779) as internal control. Note that AMPK is activated by phosphorylation so that activity of AMPK is expressed by the ratio between phosphorylated (pAMPK) and total AMPK concentrations (32). All antibody and protein concentrations were optimized following the manufacturer's recommendations.…”