Aim: 

The administration of 3,5-diiodo-L-thyronine (T₂) to rats receiving a high-fat diet (HFD) for 1 month, reduces adiposity and body weight gain by increasing hepatic fatty acid oxidation. This is associated with AMP-activated protein kinase (AMPK) phosphorylation.

Methods: 

to gain insight into the effects of T₂ on fat handling, we studied the temporal relationship between fatty acids oxidation in liver and their release from white adipose tissue (WAT). Moreover, the role of AMPK phosphorylation in the organ specific response was assessed.

Results: 

T₂ rapidly (within 6h) stimulated mitochondrial fatty acid oxidation in liver without induction of AMPK Thr¹⁷²/acetyl CoA carboxylase (ACC) Ser⁷⁹ phosphorylation and of carnitine palmitoyl transferase (CPT) activity. This effect persisted also after inhibition of AMPK phosphorylation with Compound C. In the WAT, on the other hand, phosphorylation of AMPK and its target residue Ser⁵⁶⁵ of hormone sensitive lipase HSL (inhibiting its activity) as well as Ser⁵⁶³ (activating HSL) was rapidly increased (1 day), but no increase in lipolysis was observed. After 1 week, as a consequence of a decrease in phosphorylation of AMPK as well as HSL Ser⁵⁶⁵ , an increase in both HSL phosphorylation at Ser563 and lipolysis was observed.

Conclusions: 

The administration of T2 to HFD rats is able to affect lipid handling both in liver and WAT in a organ specific manner. AMPK was affected earlier in WAT and later in liver, possibly playing different roles.