Recently we have demonstrated a direct effect of iodothyronines on excess fat storage in rat hepatocytes. Lipid excess is stored in intracellular lipid droplets (LDs) whose surface is coated by LD-associated proteins of the PAT-family (among them ADRP,TIP47, OXPAT). PAT proteins regulate LD turnover by modulating lipolysis and are differentially expressed in liver steatosis. Our hypothesis is that hypolipemic effect exerted by iodothyronines might occur also through modulation of PAT protein expression.

Primary cultures of adult rat hepatocytes pre-exposed to an oleate/palmitate mixture (fatty hepatocytes), were exposed to T2 or T3. Lipid accumulation and LD morphology were assessed by Oil Red-O staining, mRNA expression of PAT proteins was assessed by quantitative real-time RT-PCR.

In fatty hepatocytes the increase in lipid content and LD size was associated with an increased expression of ADRP and TIP47 whereas no significant changes in OXPAT expression was observed. Lipid content and number/size of LDs decreased after 24h exposure to both T2 or T3. Whereas the hypolipemic effect of T2 was associated with a down-regulation of ADRP and TIP47 and with an up-regulation of OXPAT expression with respect to fatty hepatocytes, a down-regulation of all the three PAT proteins occurred with T3. The distinct transcription profile observed for the three PAT proteins as a response to T2 or T3 might reflect the different mechanisms through which the two iodothyronines act on lipid accumulation in cultured hepatocytes.