Effect Of Leptin On Hepatic Expression And Activity Of Iodothyronine Deiodinases In The Chicken

Thyroid hormones (THs) are important for chicken growth and development, and serum levels of THs are regulated mainly by iodothyronine deiodinases. Previous studies in our laboratory indicated that in ovo leptin administration improved postnatal growth and development of broiler chickens. However, it is not clear whether this effect is associated with changes in serum levels of THs, as well as expression and activity of hepatic iodothyronine deiodinases in broiler chickens. The present study was conducted to investigate the effects of in ovo leptin administration on posthatch serum THs and hepatic expression and activity of iodothyronine deiodinases in broiler chickens, and to elucidate the possible mechanisms.1 Effect of in ovo leptin administration on serum THs levels and hepatic expression and activity of iodothyronine deiodinases in the chickenFertilized Sanhuang breeder eggs were divided into two groups:Leptin (Lep) treated group was injected with 5μg of recombinant mice Leptin in 100μL of phosphate buffered saline (PBS) into the albumen of eggs and Control (Con) group was injected with 100μL of PBS. On day 21 of posthatch development, birds from each group were killed by decapitation, samples of liver and blood were collected. Our results showed that leptin in ovo injection significantly increased serum levels of total and free triiodothyronine (TT3 and FT3), while serum level of total thyroxin (T4) remained unchanged. These changes were seen only in males. Accordingly, hepatic mRNA expresion and activity of D1, the iodothyronine deiodinase that converts T4 to T3, were significantly increased in leptin-treated chickens, while that of D3, the iodothyronine deiodinase that converts T3 to T2 or T4 to rT3, were significantly decreased. Such alterations were also mostly observed in males. These data suggest that in ovo leptin administration affects serum levels of THs by modifying hepatic expression and activity of iodothyronine deiodinase in a gender-specific fashion.2 Effect of leptin on hepatic expression and activity of iodothyronine deiodinases in primary culture of chicken embryo hepatocytes and signal pathways involvedThree signaling pathways, JAK-STAT, MAPK and PI3K, are reported to be involved in the effect of leptin, but pathway mediating the effect of leptin on hepatic iodothyronine deiodinase expression was not clear. In the present study, we examined the expression and activity of D1 and D3 in primary culture of chicken embryo hepatocyte (CEHs) treated with different doses of leptin. The inhibitors for three signaling pathways, JAK2 inhibitor AG490, PI3K inhibitor LY294002 and ERK inhibitor PD98095, were used for the identification of involved signaling pathway. Our results showed that leptin (1-100 ng/ml) significantly up-regulated D1 mRNA and activity, whereas D3 mRNA and activity were decreased. The PI3K inhibitor, LY294002, blocked leptin-stimulated D1 expression, but none of the three inhibitors blocked leptin's-inhibitory effect on D3 expression. In summary, these findings suggest that leptin up-regulates D1 expression in chicken embryo hepatocytes through activation of PI3K/AKT signaling pathway, yet the signaling pathway responsible for the leptin-induced inhibition of D3 expression awaits further investigation.