Food deprivation reduces sensitivity of liver Igf1 synthesis pathways to growth hormone in juvenile gopher rockfish (Sebastes carnatus).

Growth hormone (Gh) regulates growth in part by stimulating the liver to synthesize and release insulin-like growth factor-1 (Igf1), which then promotes somatic growth. However, for fish experiencing food limitation, elevated blood Gh can occur even with low circulating Igf1 and slow growth, suggesting that nutritional stress can alter the sensitivity of liver Igf1 synthesis pathways to Gh. Here, we examined how recent feeding experience affected Gh regulation of liver Igf1 synthesis pathways in juvenile gopher rockfish (Sebastes carnatus) to illuminate mechanisms underlying the nutritional modulation of Igf1 production. Juvenile gopher rockfish were maintained under conditions of feeding or complete food deprivation (fasting) for 14 d and then treated with recombinant sea bream (Sparus aurata) Gh or saline control. Gh upregulated hepatic igf1 mRNA levels in fed fish but not in fasted fish. The liver of fasted rockfish also showed a lower relative abundance of gene transcripts encoding teleost Gh receptors 1 (ghr1) and 2 (ghr2), as well as reduced protein levels of phosphorylated janus tyrosine kinase 2 (pJak2) and signal transducer and activator of transcription 5 (pStat5), which function to induce igf1 gene transcription following Gh binding to Gh receptors. Relative hepatic mRNA levels for suppressors of cytokine signaling (Socs) genes socs2, socs3a, and socs3b were also lower in fasted rockfish. Socs2 can suppress Gh activation of Jak2/Stat5, and fasting-related variation in socs expression may reflect modulated inhibitory control of igf1 gene transcription. Fasted rockfish also had elevated liver mRNA abundances for lipolytic hormone-sensitive lipase 1 (hsl1) and Igf binding proteins igfbp1a, -1b and -3a, reduced liver mRNAs encoding igfbp2b and an Igfbp acid labile subunit-like (igfals) gene, and higher transcript abundances for Igf1 receptors igf1ra and igf1rb in skeletal muscle. Together, these findings suggest that food deprivation impacts liver Igf1 responsiveness to Gh via multiple mechanisms that include a downregulation of hepatic Gh receptors, modulation of the intracellular Jak2/Stat5 transduction pathway, and possible shifts in Socs-inhibitory control of igf1 gene transcription, while also demonstrating that these changes occur in concert with shifts in liver Igfbp expression and muscle Gh/Igf1 signaling pathway components.

Nutritional status affects Igf1 regulation of skeletal muscle myogenesis, myostatin, and myofibrillar protein degradation pathways in gopher rockfish (Sebastes carnatus).

Insulin-like growth factor-1 (Igf1) regulates skeletal muscle growth in fishes by increasing protein synthesis and promoting muscle hypertrophy. When fish experience periods of insufficient food intake, they undergo slower muscle growth or even muscle wasting, and those changes emerge in part from nutritional modulation of Igf1 signaling. Here, we examined how food deprivation (fasting) affects Igf1 regulation of liver and skeletal muscle gene expression in gopher rockfish (Sebastes carnatus), a nearshore rockfish of importance for commercial and recreational fisheries in the northeastern Pacific Ocean, to understand how food limitation impacts Igf regulation of muscle growth pathways. Rockfish were either fed or fasted for 14 d, after which a subset of fish from each group was treated with recombinant Igf1 from sea bream (Sparus aurata). Fish that were fasted lost body mass and had lower body condition, reduced hepatosomatic index, and lower plasma Igf1 concentrations, as well as a decreased abundance of igf1 gene transcripts in the liver, increased hepatic mRNAs for Igf binding proteins igfbp1a, igfbp1b, and igfbp3a, and decreased mRNA abundances for igfbp2b and a putative Igf acid labile subunit (igfals) gene. In skeletal muscle, fasted fish showed a reduced abundance of intramuscular igf1 mRNAs but elevated gene transcripts encoding Igf1 receptors A (igf1ra) and B (igf1rb), which also showed downregulation by Igf1. Fasting increased skeletal muscle mRNAs for myogenin and myostatin1, as well as ubiquitin ligase F-box only protein 32 (fbxo32) and muscle RING-finger protein-1 (murf1) genes involved in muscle atrophy, while concurrently downregulating mRNAs for myoblast determination protein 2 (myod2), myostatin2, and myogenic factors 5 (myf5) and 6 (myf6 encoding Mrf4). Treatment with Igf1 downregulated muscle myostatin1 and fbxo32 under both feeding conditions, but showed feeding-dependent effects on murf1, myf5, and myf6/Mrf4 gene expression indicating that Igf1 effects on muscle growth and atrophy pathways is contingent on recent food consumption experience.

Insulin-like growth factor-1 (Igf1) signaling responses to food consumption after fasting in the Pacific rockfish Sebastes carnatus.

Fish adjust rates of somatic growth in the face of changing food consumption. As in other vertebrates, growth in fish is regulated by the growth hormone (Gh)/insulin-like growth factor-1 (Igf1) endocrine axis, and changes in food intake impact growth via alterations to Gh/Igf1 signaling. Understanding the time course by which the Gh/Igf1 axis responds to food consumption is crucial to predict how rapidly changes in food abundance might lead to altered growth dynamics. Here, we looked at the response times of plasma Igf1 and liver Igf1 signaling-associated gene expression to refeeding after food deprivation in juvenile gopher rockfish (Sebastes carnatus), one of several species of northern Pacific Ocean Sebastes rockfishes targeted by fisheries or utilized for aquaculture. Gopher rockfish were fasted for 30 d, after which a subset was fed to satiation for 2 h, while other rockfish continued to be fasted. Refed fish exhibited higher hepatosomatic index (HSI) values and increased Igf1 after food consumption. Gene transcripts for Gh receptor 1 (ghr1), but not ghr2, increased in the liver 2-4 d after eating. Transcripts encoding igf1also increased in the liver of refed fish by 4 d after feeding, only to return to levels similar as continually fasted rockfish by 9 d after feeding. Liver mRNA abundances for Igf binding protein (Igfbp) genes igfbp1a, igfbp1b, and igfbp3a declined within 2 d of feeding. These findings provide evidence that circulating Igf1 in rockfish reflects a fish's feeding experience within the previous few days, and suggest that feeding-induced increases in Igf1 are being mediated in part by altered liver sensitivity to Gh due to upregulated Gh receptor 1 expression.

Effects of food deprivation on plasma insulin-like growth factor-1 (Igf1) and Igf binding protein (Igfbp) gene transcription in juvenile cabezon (Scorpaenichthys marmoratus).

The growth hormone (GH)/insulin-like growth factor (Igf) endocrine axis regulates somatic growth in the face of changing environmental conditions. In actinopterygian fishes, food availability is a key modulator of the somatotropic axis, with lower food intake generally depressing liver Igf1 release to diminish growth. Igf1 signaling, however, also involves several distinct IGF binding proteins (Igfbps), and the functional roles of many of these Igfbps in affecting growth during shifting food availability remain uncertain. Here, we tested how complete food deprivation (fasting) affected gene transcription for paralogs of all six types of Igfbps in the liver and fast-twitch skeletal muscle of cabezon (Scorpaenichthys marmoratus), a nearshore marine fish important for recreational fisheries in the eastern North Pacific Ocean. Juvenile cabezon were maintained as either fed (6% mass food⋅g fish wet mass-1⋅d-1) or fasted for 14 d. Fasted fish exhibited a lower body condition (K), a depressed mass-specific growth rate (SGR), and reduced plasma concentrations of Igf1. In the liver, fasting reduced the relative abundance of gene transcripts encoding Igfbps igfbp2a and igfbp2b, while significantly elevating mRNA levels for igfbp1a, igfbp1b, igfbp3b, and igfbp4. Fasting also reduced hepatic mRNA levels of GH receptor-1 (ghr1) - but not GH receptor-2 (ghr2) - supporting the idea that changes in liver sensitivity to GH may underlie the decline in plasma Igf1 during food deprivation. In skeletal muscle, fasting downregulated gene transcripts encoding igf1, igfbp2b, igfbp5b, and igfbp6b, while also upregulating mRNAs for igf2 and ghr2. These data demonstrate isoform-specific regulation of Igfbps in liver and skeletal muscle in cabezon experiencing food deprivation and reinforce the idea that the repertoire of duplicated Igfbp genes that evolved in actinopterygian fishes supports a diverse scope of endocrine and paracrine functions.