Role of the PGC-1 family in the metabolic adaptation of goldfish to diet and temperature

Abstract

SUMMARYIn mammals, the peroxisome proliferator-activated receptor (PPAR) γ coactivator-1 (PGC-1) family members and their binding partners orchestrate remodelling in response to diverse challenges such as diet, temperature and exercise. In this study, we exposed goldfish to three temperatures (4, 20 and 35°C) and to three dietary regimes (food deprivation, low fat and high fat) and examined the changes in mitochondrial enzyme activities and transcript levels for metabolic enzymes and their genetic regulators in red muscle, white muscle, heart and liver. When all tissues and conditions were pooled, there were significant correlations between the mRNA for the PGC-1 coactivators (both α and β) and mitochondrial transcripts (citrate synthase), metabolic gene regulators including PPARα, PPARβ and nuclear respiratory factor-1 (NRF-1). PGC-1β was the better predictor of the NRF-1 axis, whereas PGC-1α was the better predictor of the PPAR axis (PPARα, PPARβ, medium chain acyl CoA dehydrogenase). In contrast to these intertissue/developmental patterns, the response of individual tissues to physiological stressors displayed no correlations between mRNA for PGC-1 family members and either the NRF-1 or PPAR axes. For example, in skeletal muscles, low temperature decreased PGC-1α transcript levels but increased mitochondrial enzyme activities (citrate synthase and cytochrome oxidase) and transcripts for COX IV and NRF-1. These results suggest that in goldfish, as in mammals, there is a regulatory relationship between (i) NRF-1 and mitochondrial gene expression and (ii) PPARs and fatty acid oxidation gene expression. In contrast to mammals, there is a divergence in the roles of the coactivators, with PGC-1α linked to fatty acid oxidation through PPARα, and PGC-1β with a more prominent role in mediating NRF-1-dependent control of mitochondrial gene expression, as well as distinctions between their respective roles in development and physiological responsiveness.

Coordination of cytochrome c oxidase gene expression in the remodelling of skeletal muscle

“…However, there is better support for a role for NRF-1 as a master regulator in fish. Previous studies have shown a fairly close relationship between NRF-1 mRNA level and mitochondrial changes (LeMoine et al, 2008;Orczewska et al, 2010).…”

“…COX enzyme activity has previously been reported for these treatment groups (LeMoine et al, 2008). Archived cDNA from that study was used for the RNA analyses in the present study.…”

“…Goldfish (Carrasius auratus, Linnaeus) were acclimated to 4 and 35°C, as described in a previous study (LeMoine et al, 2008). COX enzyme activity has previously been reported for these treatment groups (LeMoine et al, 2008).…”

“…In mammals, PGC-1 is thought to play the role of master regulator of mitochondrial biogenesis in tissues (Puigserver and Spiegleman, 2003). PGC-1 transcript levels have been measured in a number of fish studies assessing its role as a master regulator of mitochondrial differences arising between tissues, such as muscle fibre types in goldfish (LeMoine et al, 2008), and physiological states, such as cold acclimation in goldfish (LeMoine et al, 2008) and three-spine stickleback (Orczewska et al, 2010), and exercise training in zebrafish (McClelland et al, 2006). There is some evidence that the PGC-1 gene in fish experienced mutations that may have altered its capacity to interact with NRF-1.…”

“…However, recent studies have questioned the importance of PGC-1 in coordinating gene expression in fish (LeMoine et al, 2008). This coactivator has experienced an elevated rate of evolution in fish, and has incurred multiple insertional mutations in the domain that interacts with NRF-1 (LeMoine et al, 2010a).…”