Insulin-like growth factor-I and genetic effects on indexes of protein degradation in response to feed deprivation in rainbow trout (Oncorhynchus mykiss)

Abstract

This study determined the effect of genetic variation, feed deprivation, and insulin-like growth factor-I (IGF-I) on weight loss, plasma IGF-I and growth hormone, and indexes of protein degradation in eight full-sibling families of rainbow trout. After 2 wk of feed deprivation, fish treated with IGF-I lost 16% less (P < 0.05) wet weight than untreated fish. Feed deprivation increased growth hormone (P < 0.05) and decreased IGF-I (P < 0.05), but hormone levels were not altered by IGF-I. Plasma 3-methylhistidine concentrations were not affected by IGF-I but were decreased after 2 wk (P < 0.05) and increased after 4 wk (P < 0.05) of feed deprivation. In white muscle, transcript abundance of genes in the ubiquitin-proteasome, lysosomal, and calpain- and caspase-dependent pathways were affected by feed deprivation (P < 0.05). IGF-I prevented the feed deprivation-induced upregulation of MAFbx (F-box) and cathepsin transcripts and reduced abundance of proteasomal mRNAs (P < 0.05), suggesting that reduction of protein degradation via these pathways may be partially responsible for the IGF-I-induced reduction of weight loss. Family variations in gene expression, IGF-I concentrations, and weight loss during fasting suggest genetic variation in the fasting response, with considerable impact on regulation of proteolytic pathways. These data indicate that nutrient availability, IGF-I, and genetic variation affect weight loss, in part through alterations of proteolytic pathways in rainbow trout, and that regulation of genes within these pathways is coordinated in a way that supports a similar physiological response.

Mechanisms of protein degradation in mantle muscle and proposed gill remodeling in starvedSepia officinalis

“…Regardless, significant changes in three components of the UPS in mantle strongly cases); heart-aspartate aminotransferase (AspAT) and alanine aminotransferase (AlAT), 3; heart -glutamate dehydrogenase (GDH) and citrate synthase (CS), 5 (fed) and 8 (starved); mantle and retractor, 4 in all cases, except CS, for which mantle is 2 and retractor is 3. suggest activation of this process, which would result in proteolysis, leading to the production of amino acids to fuel metabolism. Three studies with rainbow trout also report no change in 20S proteasome activity in muscle following 14 days of starvation, similar to the current finding with S. officinalis (9,23,35). Moreover, increases were reported in the expression of ubiquitin-protein ligases (9,35) and in polyubiquinated protein (35), consistent with activation of the UPS.…”

“…Three studies with rainbow trout also report no change in 20S proteasome activity in muscle following 14 days of starvation, similar to the current finding with S. officinalis (9,23,35). Moreover, increases were reported in the expression of ubiquitin-protein ligases (9,35) and in polyubiquinated protein (35), consistent with activation of the UPS. Although Martin et al (23) present the argument, based primarily on a decrease in total ubiquitin protein, that 14 days of starvation in rainbow trout leads to a decrease in proteolysis by the UPS in muscle, more recent findings do not support this viewpoint.…”

“…This finding suggests that the lysosomal pathway of protein degradation is also activated to provide amino acids for energy metabolism. Starvation in rainbow trout resulted in increased expression of cathepsin L transcript in muscle (enzyme activity was not reported) (9) and activity of cathepsin D in muscle of Atlantic cod (9,16). Although there may be minor variations on this theme, it appears that the lysosomal protein degradation pathway is activated at some point during starvation in muscle of both S. officinalis and fishes.…”

Alteration in expression of atrogenes and IGF-1 induced by fasting in Nile tilapia Oreochromis niloticus juveniles

“…In rainbow trout treated with IGF-1 during feed deprivation, inhibition of atrogin-1 expression was observed, along with a reduction of proteolytic activity (Cleveland et al 2009). In the present study, IGF-1 receptor expression was upregulated significantly during 1-3 weeks of fasting in F1, F2, and F3, compared to FC.…”

“…It is well established in vertebrates that insulin-like growth factor-1 stimulates activation of the PI3 K/Akt/ mTOR cascade, increasing protein synthesis and hypertrophic muscle growth (Engert et al 1996;Zhang et al 2008;Duan et al 2010), and inactivates FOXO transcription factors, decreasing the expression of atrogin-1/ MAFbx and MuRF1 (Sacheck et al 2004;Edstron et al 2006;Cleveland et al 2009;Fuentes et al 2013). In this context, the lower IGF-1 expression observed in fasted tilapia juveniles likely plays a role in the higher expression of MuRF1 and atrogin-1, consequently inducing muscle atrophy, over extended periods of time, and blocking somatic growth.…”