Involvement of PGC-1, NRF-1, and NRF-2 in metabolic response by rat liver to hormonal and environmental signals.

We studied liver oxidative capacity and O2 consumption in hypothyroid rats treated for 10 days with T4, or T3, or treated for 10 days with T3 and exposed to cold for the last 2 days. The metabolic response of homogenates and mitochondria indicated that all treatments increased the synthesis of respiratory chain components, whereas only the cold-induced mitochondrial proliferation. Determination of mRNA and protein expression of transcription factor activators, such as NRF-1 and NRF-2, and coactivators, such as PGC-1, showed that mRNA levels, except PGC-1 ones, were not related to aerobic capacities. Conversely, a strong correlation was found between cytochrome oxidase activity and PGC-1 or NRF-2 protein levels. Such a correlation was not found for NRF-1. Our results strongly support the view that in rat liver PGC-1 and NRFs are responsible for the iodothyronine-induced increases in respiratory chain components, whereas their role in cold-induced mitochondrial proliferation needs to be further on clarified.