Aim: 

3,5-diiodothyronine (T2) powerfully reduces adiposity in rats fed high fat diet stimulating hepatic fatty acids oxidation and increasing mitochondrial uncoupling. We studied how the nuclear, cytolasmic and mitochondrial hepatic phenotype respond in terms of protein expression to T2-treatment, by combining blue native (BN) and 2D-E.

Methods: 

Standard diet -fed control rats (N), high-fat diet-(HFD) fed rats and T2-long term (30 days) treated HDF rats (HFD+T2) were used throughout.

Results: 

We obtained an integrated view of the phenotypic/ metabolic adaptation (oxidative stress, lipid metabolism, urea cycling, amminoacid metabolism, respiratory chain and proteosome) occurring in liver proteome during HFD and after T2-treatment. Interestingly, T2 counteracted several changes induced by HFD. BN and subsequent in gel-activity of OXPHOS complexes, revealed a significantly modified profile of individual complexes in HFD mitochondria vs N ones. This pattern was normalized in mitochondria from T2-treated animals with a concomitant higher oxidative capacity.

Conclusion: 

In a situation of cellular and mitochondrial overload of fatty acids, T2 is able to affect liver proteome in a way putatively associated with no-steatosis following HFD.