Abstract
Autophagy functions as an important catabolic mechanism by mediating the turnover of intracellular organelles and protein complexes through a lysosome dependent degradative pathway. Although the induction of autophagy by starvation has been extensively studied, we still know very little about how autophagy is regulated under normal nutritional conditions. The purpose of the present study was to characterize both in vivo and in vitro the response of the autophagy-lysosomal degradative pathway to nutrient (amino acids and carbohydrates) availability in the muscle of the carnivorous rainbow trout. We report that meal feeding is accompanied by a rapid activation of Akt, FoxO1 and the Target of Rapamycin (TOR) signaling pathways and a concomitant decrease of autophagosome formation. We also show that this effect occurs only when the proportion of dietary proteins increases at the expense of carbohydrates. Concurrently, our in vitro study on primary culture of trout muscle cells demonstrates an opposite effect of amino acids and glucose on the regulation of autophagy-lysosomal pathways. More specifically, the addition of amino acids in cell culture medium inhibited the formation of autophagosomes, whereas the addition of glucose had an opposite effect. The effect of amino acids was accompanied by an activation of TOR, considered as an important regulator of autophagosomal formation. However, the mechanisms involved in the effect of glucose were independent of Akt, TOR and AMPK and remain to be determined. Together, these results demonstrated the specific role of macronutrients as well as that of their interactions in the regulation of autophagy and highlight the interest to consider the macronutrient composition of the diets in the control of this degradative pathway.
Highlights
Protein degradation is a highly regulated and selective process that depends on the activation of conserved proteolytic pathways [1]
We analyzed the postprandial response of the autophagosomal marker LC3-II as well as that of its upstream factors Akt, FoxO1, Target of Rapamycin (TOR) and AMPK to a single meal in the muscle of rainbow trout
These results show for the first time the postprandial response of autophagy to feeding in the muscle of rainbow trout
Summary
Protein degradation is a highly regulated and selective process that depends on the activation of conserved proteolytic pathways [1]. Two major proteolytic systems are thought to (co-) operate in the skeletal muscle of vertebrates, the ubiquitin/proteasomal pathway and the autophagic/lysosomal pathway [2]. The ubiquitin/proteasomal pathway has been well documented and has long been considered to be the primary system involved in muscle atrophy [3,4,5,6,7]. Until recently, the role of autophagy in skeletal muscle protein degradation has been largely ignored. Recent work by Masiero et al, has demonstrated that basal autophagy is critical to muscle homeostasis, since it is responsible for the removal of protein aggregates and damaged mitochondria [8]. Mice with muscle-specific suppression of autophagy exhibited severe muscle weakness, atrophy and decreased muscle contractility [8]
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