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Title: Insulin-like growth factor-I treatment and genetic variation affect changes in indices of protein degradation in response to food deprivation in rainbow trout (Oncorhynchus mykiss)

Author
item Cleveland, Beth
item Weber, Gregory - Greg
item BLEMINGS, KENNETH - WEST VIRINIA UNIVERSITY
item Silverstein, Jeffrey

Submitted to: American Journal of Physiology - Regulatory Integrative & Comparative Physiology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 8/27/2009
Publication Date: 9/2/2009
Citation: Cleveland, B.M., Weber, G.M., Blemings, K.P., Silverstein, J. 2009. Insulin-like growth factor-I treatment and genetic variation affect changes in indices of protein degradation in response to food deprivation in rainbow trout (Oncorhynchus mykiss). American Journal of Physiology - Regulatory Integrative & Comparative Physiology. 297:R1332-R1342.

Interpretive Summary: Protein represents the main component of the biomass of the rainbow trout, therefore rates of protein turnover can have tremendous impact on the growth, weight loss, and feed efficiency of the fish. Protein turnover is determined by the rates of protein synthesis as well as the rates of protein degradation (proteolysis). Understanding how these rates respond to and are regulated by physiological changes will contribute to our knowledge of how changes in protein metabolism affect performance. This study investigates the ability of insulin-like growth factor (IGF-I) to affect weight loss during feed deprivation through the regulation ofproteolytic genes in white muscle of rainbow trout. Understanding how nutrient deprivation and IGF-I affect proteolytic pathways will provide a better comprehension of how these pathways influence protein turnover. Additionally, the integration of full-sib families into the experimental design will determine if genetic variation contributes to responses to feed deprivation and IGF-I. Results from the present study indicated that feed deprivation affected the expression of genes in all four proteolytic pathways. Treatment with IGF-I reduced expression of genes in the ubiquitin-proteosomal and lysosomal proteolytic pathways, suggesting that reducing protein degradation via down regulation of these pathways may be partially responsible for IGF-I induced reduction in weight loss. Family variations in gene expression and weight loss suggests that genetic variation can contribute to differences in protein degradation. Collectively, these results suggest that selecting for fish with relatively lower levels of proteolysis through the ubiquitin-proteosome and lysosomal pathways may potentially be a method for improving protein accretion and thereby feed efficiency and growth in a selective breeding program.

Technical Abstract: This study determined the effect of genetic variation, feed deprivation and IGF-I treatment on weight loss, plasma IGF-I and GH, and indices of protein degradation in eight full-sibling families of rainbow trout. After two weeks of feed deprivation, fish treated with IGF-I lost 16% less (P<0.05) wet weight than untreated fish. Feed deprivation increased GH (P<0.05) and decreased IGF-I (P<0.05) but hormone levels were not altered by IGF-I treatment. Plasma 3-methylhistidine concentrations were not affected by IGF-I but were decreased after two weeks (P<0.05) and increased after four weeks (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). Treatment with 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 the reduction of protein degradation via these pathways may be partially responsible for the IGF-I induced reduction in weight loss. Family variations in gene expression, plasma GH and IGF-I concentrations, and weight loss during fasting suggest genetic variation in the fasting response with considerable impact on the regulation of proteolytic pathways. These data indicate that nutrient response with considerable impact on the regulation of proteolytic pathways. These data indicate that nutrient availability, IGF-I, and genetic variation affect weight loss in part through alterations in proteolytic pathways in rainbow trout and that regulation of genes within these pathways is coordinated in a way that supports a similar physiological response.