Chronic stress inhibits growth and induces proteolytic mechanisms through two different nonoverlapping pathways in the skeletal muscle of a teleost fish

Abstract

Chronic stress detrimentally affects animal health and homeostasis, with somatic growth, and thus skeletal muscle, being particularly affected. A detailed understanding of the underlying endocrine and molecular mechanisms of how chronic stress affects skeletal muscle growth remains lacking. To address this issue, the present study assessed primary (plasma cortisol), secondary (key components of the GH/IGF system, muscular proteolytic pathways, and apoptosis), and tertiary (growth performance) stress responses in fine flounder ( Paralichthys adspersus) exposed to crowding chronic stress. Levels of plasma cortisol, glucocorticoid receptor 2 ( gr2), and its target genes ( klf15 and redd1) mRNA increased significantly only at 4 wk of crowding ( P < 0.05). The components of the GH/IGF system, including ligands, receptors, and their signaling pathways, were significantly downregulated at 7 wk of crowding ( P < 0.05). Interestingly, chronic stress upregulated the ubiquitin-proteasome pathway and the intrinsic apoptosis pathways at 4wk ( P < 0.01), whereas autophagy was only significantly activated at 7 wk ( P < 0.05), and meanwhile the ubiquitin-proteasome and the apoptosis pathways returned to control levels. Overall growth was inhibited in fish in the 7-wk chronic stress trial ( P < 0.05). In conclusion, chronic stress directly affects muscle growth and downregulates the GH/IGF system, an action through which muscular catabolic mechanisms are promoted by two different and nonoverlapping proteolytic pathways. These findings provide new information on molecular mechanisms involved in the negative effects that chronic stress has on muscle anabolic/catabolic signaling balance.

Insulin-Like Growth Factor-Binding Proteins of Teleost Fishes

“…Similar results were observed in fine flounder skeletal muscle, where igfbp-6b expression decreased in response to feeding immediately post-fasting, although expression then increased during long-term refeeding ( 88 ). However, igfbp-6b was repressed in fine flounder skeletal muscle in response to stress ( 94 ), which is less consistent with a negative role in growth. Conversely, in Atlantic salmon myotubes treated with dexamethasone, igfbp-6a1 was downregulated, while igfbp-6b2 was upregulated, highlighting complex functions that cannot be easily interpreted without functional data ( 57 ).…”

“…By contrast, treatment with dexamethasone, known to enhance catabolism, led to an increase in igfbp-2a expression in salmon skeletal muscle myotubes ( 57 ). Despite not distinguishing teleost paralogs, recent work revealed upregulation of skeletal muscle igfbp-2 expression in fine flounder ( Paralichthys adspersus ), concomitant to a rise in blood cortisol ( 94 ). Differences in Igfbp-2 expression across studies suggest a complex role for this Igfbp family member in teleost growth, dependent on both physiological and species context.…”

“…Similarly, in coho salmon ( Oncorhynchus kisutch ), igfbp-3a1 muscle expression was increased by Gh transgenesis ( 103 ), again supporting a growth-promoting role. However, stress caused a downregulation of igfbp-3b gene expression in skeletal muscle of fine flounder ( 94 ), which is inconsistent with a role in growth inhibition.…”

“…Studies of Igfbp-4 expression in response to stress also suggest a growth-promoting role. For instance, addition of dexamethasone to Atlantic salmon myotubes ( 57 ), and stress confinement in fine flounder ( 94 ) induced a significant reduction in igfbp-4 expression. Conversely, an increase in igfbp-4 expression was reported in skeletal muscle during maturation-induced atrophy in rainbow trout ( 113 ).…”

How different rearing temperatures affect growth and stress status of Siberian sturgeon Acipenser baerii larvae

“…Chronic stress has a deleterious effect on animal health and homeostasis, with somatic growth, and therefore skeletal muscle, being particularly affected (Valenzuela et al ., ). Indeed, in fish as in mammals, cortisol leads to catabolic and antianabolic effects which, in turn, delay somatic growth (Ma et al ., ), but a detailed understanding of the core endocrine and molecular mechanisms underlying how chronic stress affects skeletal muscle growth is lacking (Valenzuela et al ., ).…”