Thyroid hormone (T3) stimulates various metabolic pathways and the hepatic 
actions of T3 are mediated primarily through the thyroid hormone receptor beta 
(TRβ). Hypothyroidism has been linked with low grade inflammation, elevated risk 
of hepatic steatosis and atherosclerosis. Secretory phospholipases (sPLA2) are 
associated with inflammation, hyperlipidemia and atherosclerosis. Due to 
potential linkage between thyroid hormone and sPLA2, we investigated the effect 
of thyroid hormone status on the regulation of secretory phospholipases in mice, 
rats and human liver. T3 suppressed the expression of the sPLA2 group IIa 
(PLA2g2a) gene in the liver of BALB/c mice and C57BL/6 transgenic mice 
expressing the human PLA2g2a. PLA2g2a was elevated with hypothyroidism and high 
fat diets which may contribute to the low grade inflammation associated with 
hypothyroidism and diet induced obesity. We also examined the effects of the TRβ 
agonist eprotirome on hepatic gene regulation. We observed that eprotirome 
inhibited the expression of selected sPLA2 genes and furthermore the cytokine 
mediated induction PLA2g2a was suppressed. In addition, eprotirome induced genes 
involved in fatty acid oxidation and cholesterol clearance while inhibiting 
lipogenic genes. Our results indicate that in vivo thyroid hormone status 
regulates the abundance of sPLA2 and the inhibition of PLA2g2a by T3 is 
conserved across species. By regulating sPLA2 genes, T3 may impact processes 
associated with atherosclerosis and inflammation and TRβ agonists may ameliorate 
inflammation and hyperlipidemia.