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 02 consumption in hypothyroid rats treated for 10 days with T-4, or T-3, 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. (C) 2009 Elsevier Ireland Ltd. All rights reserved.