3,5-Diiodo-L-Thyronine Administration To Hypothyroid Rats Rapidly Enhances Fatty Acid Oxidation Rate and Bioenergetic Parameters in Liver Cells

Growing evidence shows that, among triiodothyronine derivatives, 3,5 diiodo-L-thyronine (T 2 ) plays an important role in energy metabolism and fat storage. In the present study, short-term effects of T 2 administration to hypothyroid rats on fatty acid oxidation rate and bioenergetic parameters were investigated. Within 1 h following T 2 injection, state 3 and state 4 respiration rates, which were reduced in hypothyroid mitochondria, were noticeably increased particularly in succinate- with respect to glutamate/malate-energized mitochondria. Maximal respiratory activity, observed when glutamate/malate/succinate were simultaneously present in the respiratory medium, was significantly stimulated by T 2 treatment. A T 2 -induced increase in respiratory rates was also observed when palmitoyl-CoA or L-palmitoylcarnitine were used as substrates. No significant change in respiratory control index and ADP/O ratio was observed. The activities of the mitochondrial respiratory chain complexes, especially Complex II, were increased in T 2 -treated rats. In the latter, Complex V activities, assayed in both ATP synthesis and hydrolysis direction, were enhanced. The rate of fatty acid oxidation, followed by conversion of [ 14 C]palmitate to CO 2 and ketone bodies, was higher in hepatocytes isolated from T 2 -treated rats. This increase occurs in parallel with the raise in the activity of carnitine palmitoyltransferase-I, the rate limiting enzyme of fatty acid β-oxidation, assayed in situ in digitonin-permeabilized hepatocytes. Overall, these results indicate that T 2 rapidly increases the ability of mitochondria to import and oxidize fatty acids. An emerging idea in the literature is the ability of T 2 to reduce adiposity and dyslipidemia and to prevent the development in liver steatosis. The results of the present study, showing a rapid T 2 -induced increase in the ability of mitochondria to import and oxidize fatty acids, may contribute to understand the biochemical mechanisms of T 2 -metabolic effects.