Nutritional status modulates plasma leptin, AMPK and TOR activation, and mitochondrial biogenesis: Implications for cell metabolism and growth in skeletal muscle of the fine flounder

Insight of how growth and metabolism in skeletal muscle are related is still lacking in early vertebrates. In this context, molecules involved in these processes, such as leptin, AMP-activated protein kinase (AMPK), target of rapamicyn (TOR), peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α, and oxidative phosphorylation complexes (OXPHOS), were assessed in the skeletal muscle of a fish species. Periods of fasting followed by a period of refeeding were implemented, using the fine flounder as a model (Paralichthys adspersus). This species exhibits remarkably slow growth and food intake, which is linked to an inherent growth hormone (GH) resistance and high circulating levels of leptin. Leptin increased during fasting concomitantly with AMPK activation, which was inversely correlated with TOR activation. On the other hand, AMPK was directly correlated with an increase in PGC-1α and OXPHOS complexes contents. Dramatic changes in the activation and content of these molecules were observed during short-term refeeding. Leptin, AMPK activation, and PGC-1α/OXPHOS complexes contents decreased radically; whereas, TOR activation increased significantly. During long-term refeeding these molecules returned to basal levels. These results suggest that there is a relation among these components; thus, during fasting periods ATP-consuming biosynthetic pathways are repressed and alternative sources of ATP/energy are promoted, a phenomenon that is reversed during anabolic periods. These results provide novel insight on the control of metabolism and growth in the skeletal muscle of a non-mammalian species, suggesting that both processes in fish muscle are closely related and coordinated by a subset of common molecules.

Highlights► Study showing novel data on fish skeletal muscle growth and metabolism. ► Positive relationship between plasma leptin and AMPK during fasting and refeeding. ► Positive relationship between AMPK and PGC-1a/OXPHOS complexes. ► Negative relationship between AMPK and TOR during fasting and refeeding. ► Summarized and integrated information of molecules involve in fish muscle growth.