Mark A. Sheridan

Lipid dynamics in fish: aspects of absorption, transportation, deposition and mobilization

1. Aspects of lipid metabolism, including absorption and depositional processes, appear quite different in fish as compared to homeothermic vertebrates. 2. Dietary lipids in fish are absorbed as fatty acids and as triacylglycerols aggregated into chylomicra particles. 3. Interorgan transport of lipids, like that of mammals, consists of an exogenous (dietary) loop and an endogenous loop. 4. Fish store lipids among several depot organs, including mesenteric membranes, liver and muscle. 5. Several fast-acting and slow-acting agents modulate depot lipid mobilization. 6. Mobilized lipids may be transported in the serum as free fatty acids bound to specific carrier proteins.

Regulation of lipid metabolism in poikilothermic vertebrates

Patterns of lipid storage and utilization reflect the special life histories of the animal group. Poikilothermic vertebrates (fish, amphibians, reptiles) have evolved a number of life history patterns (smoltification, metamorphosis, hibernation) which present problems for lipid storage regulation. A general theme among poikilotherms is to store lipids among several sites (mesenteric fat, liver, muscle) as opposed to a single depot type (adipose tissue) as in homeotherms; lipids are stored primarily as triacylglycerols, but various other lipid classes also are stored and constituent fatty acids tend to be more complex (longer chain, polyunsaturated). Lipid storage is influenced by de novo lipid synthesis and by lipid deposition from various plasma lipoproteins. Lipid accumulation generally occurs in most poikilotherms during periods of feeding when plasma insulin levels are elevated. Lipid mobilization is controlled by an intracellular lipase enzyme. Lipid depletion occurs during transitional and non-feeding periods and is especially apparent during salmonid smoltification and amphibian metamorphosis.

Effects of nutritional state on in vivo lipid and carbohydrate metabolism of coho salmon, Oncorhynchus kisutch.

Juvenile coho salmon (Oncorhynchus kisutch) were placed on five dietary regimes: fed 1 week, fasted 1 week, fed 3 weeks, fasted 3 weeks, and fasted 1 week/refed 2 weeks. Plasma levels of glucose, fatty acids, insulin, glucagon, and glucagon-like peptide (GLP) and the activities of key metabolic enzymes were determined. Plasma glucose levels in the fed control groups were 98.4 +/- 3.4 (SEM) and 104.8 +/- 4.7 mg/dl at 1 and 3 weeks, respectively. Plasma glucose in the fasted 1 week group was significantly elevated to 128.8 +/- 9.2 mg/dl. Animals fasted 3 weeks or fasted 1 week/refed 2 weeks displayed plasma glucose levels similar to those of fed animals. Fasted groups possessed significantly less liver glycogen than fed or fasted/refed groups. Plasma fatty acids were elevated only after 3 weeks of fasting (from 0.39 +/- 0.04 microEq/ml to 0.61 +/- 0.06 microEq/ml). This response was reflected in elevated liver lipase activity (from 6.02 +/- 0.44 nmol fatty acid released/hr/mg protein to 14.22 +/- 0.90 units). No significant alterations in liver lipogenesis, assessed by glucose-6-phosphate dehydrogenase activity and by 3H2O incorporation into fatty acids, were observed. Gluconeogenic flux, determined indirectly through kinetic parameters of pyruvate kinase, was enhanced in animals fasted 3 weeks and in animals recovering from a 1-week fast. Plasma insulin levels were highest in fed groups (7.7 +/- 2.3 and 5.9 +/- 1.4 ng/ml at 1 week and 3 weeks, respectively) and were significantly depressed in fasted groups. Plasma levels of glucagon and GLP were also depressed in fasted groups. These results indicate that plasma glucose levels are maintained in salmon during fasting and that fasting-induced hyperlipidemia is mediated by lipolytic enzyme activity. Insulin, glucagon, and GLP may interact with these enzyme systems to coordinate nutritional metabolism of fish.

Peripheral regulation of the growth hormone-insulin-like growth factor system in fish and other vertebrates.

The growth hormone (GH)-insulin-like growth factor (IGF) system plays a major role in coordinating the growth of vertebrates including fish. Considerable research on the regulation of growth has focused on the production and secretion of GH from the pituitary. This review will synthesize recent work on regulating extrapituitary aspects of the GH-IGF system, which includes GH binding proteins (GHBP), GH receptors (GHR), IGF binding protein (IGFBP), and IGF receptors (IGFR). These components are widely distributed and they interact to coordinate growth as well as a host of other biological processes such as metabolism, osmoregulation, reproduction, behavior, and immunity. The GH-IGF system of fish is particularly interesting and complex because it consists of multiple subtypes of GHRs, IGFRs, and IGFBPs that arose through gene duplication events associated with the evolution of the teleost lineage. Peripheral regulation of the GH-IGF system results from adjusting peripheral sensitivity to GH and IGFs as well as from modulating the bioavailability and actions of GH and IGFs in target cells. Numerous chemicals, including hormones such as growth hormone, insulin, somatostatin, and sex steroids as well as a variety of transcription factors, proteases, and phosphatases, regulate the synthesis and activity of GHRs, GHBPs, IGFRs, and IGFBPs as well as the synthesis, secretion, and bioavailability of IGFs. In addition, numerous environmental factors such as nutritional state, photoperiod, stress, and temperature have dramatic effects on the expression and activity of peripheral components of the GH/IGF system. The complex regulation of these system components appears to be both organism- and tissue-specific.

Alterations in lipid metabolism accompanying smoltification and seawater adaptation of salmonid fish

Abstract During the smoltification of salmonid fish, lipids are depleted from depot sites primarily from the triacylglycerol fraction. Increases in tissue lipolytic rates and decreases in rates of lipid synthesis are among the factors responsible for lipid depletion. Lipase mediated lipid depletion has also been observed following seawater exposure. Thyroxine, cortisol, growth hormone and prolactin underlie smoltification-associated lipid depletion and are probably involved in seawater-associated alterations in lipid metabolism.

Diurnal rhythms of plasma growth hormone, somatostatin, thyroid hormones, cortisol and glucose concentrations in rainbow trout, Oncorhynchus mykiss, during progressive food deprivation

Abstract The diurnal patterns of changes in plasma cortisol, growth hormone (GH), somatostatin‐14 (SRIF), thyroid hormones (L‐thyroxine, T4 and triiodo‐L‐thyronine, T3) and glucose were investigated in rainbow trout, Oncorhynchus mykiss, both during single meal‐feeding and during a progressive fast of 13 weeks. All measured variables exhibited a diurnal pattern in fed rainbow trout, most of which appeared to be correlated with the time of feeding (30–60 min after the onset of light), while additional changes, associated with the scotophase were also found for cortisol. Although fasting had no affect on mean daily plasma cortisol or SRIF concentrations, there was a progressive increase in mean daily plasma GH concentrations and a progressive decrease in mean daily plasma thyroid hormone and glucose concentrations associated with fasting. However, for GH, significant changes were not evident until week 10 of the fast. In addition, fasting appeared to phase‐shift the diurnal patterns of plasma GH, cortisol a...

New insights into the signaling system and function of insulin in fish.

Fish have provided essential information about the structure, biosynthesis, evolution, and function of insulin (INS) as well as about the structure, evolution, and mechanism of action of insulin receptors (IR). INS, insulin-like growth factor (IGF)-1, and IGF-2 share a common ancestor; INS and a single IGF occur in Agnathans, whereas INS and distinct IGF-1 and IGF-2s appear in Chondrichthyes. Some but not all teleost fish possess multiple INS genes, but it is not clear if they arose from a common gene duplication event or from multiple separate gene duplications. INS is produced by the endocrine pancreas of fish as well as by several other tissues, including brain, pituitary, gastrointestinal tract, and adipose tissue. INS regulates various aspects of feeding, growth, development, and intermediary metabolism in fish. The actions of INS are mediated through the insulin receptor (IR), a member of the receptor tyrosine kinase family. IRs are widely distributed in peripheral tissues of fish, and multiple IR subtypes that derive from distinct mRNAs have been described. The IRs of fish link to several cellular effector systems, including the ERK and IRS-PI3k-Akt pathways. The diverse effects of INS can be modulated by altering the production and release of INS as well as by adjusting the production/surface expression of IR. The diverse actions of INS in fish as well as the diverse nature of the neural, hormonal, and environmental factors known to affect the INS signaling system reflects the various life history patterns that have evolved to enable fish to occupy a wide range of aquatic habitats.

Metabolic effects of salmon glucagon and glucagon-like peptide in coho and chinook salmon ☆

Different doses of glucagon and glucagon-like peptide (GLP) isolated from coho salmon, Oncorhynchus kisutch were tested in vivo and in vitro on juvenile coho and chinook (O. tshawytscha) salmon. Results obtained suggest an involvement of these peptides in the regulation of plasma glucose, plasma fatty acids, liver glycogen, and the hepatic enzymes: glycogen phosphorylase, pyruvate kinase, triacylglycerol lipase, and glucose-6-phosphate dehydrogenase. Metabolic effects were more enhanced in summer than either in spring or in autumn. GLP was less effective than glucagon in stimulating glycogenolysis in vivo. Salmon glucagon, especially in low concentrations, was generally more potent metabolically than mammalian (porcine/bovine) glucagon. The interaction between glucagon-family peptides and insulin seems to be different from the one described in mammals: glucagon and GLP either lowered plasma circulating levels of insulin or showed no effect. Only at the time of parr-smolt transformation did GLP slightly elevate plasma insulin levels in coho salmon.

Effects of nutritional state, insulin, and glucagon on lipid mobilization in rainbow trout, Oncorhynchus mykiss.

The effects of nutritional state, insulin, and glucagon on lipid mobilization were determined in rainbow trout, Oncorhynchus mykiss. In nutritional state experiments, fish were either fed continuously (except 24 to 36 hr prior to experimentation) with commercial trout chow or fasted for 4 weeks. Lipase activity in liver tissue isolated from fasted fish and cultured for 5 hr was greater than that in tissue isolated from fed fish and cultured. The presence of glucose (5.55 mM) in the incubation medium accentuates lipolytic activity in both liver and adipose tissue. Hormone response was assessed both in vivo and in vitro. Salmon insulin was injected into anesthetized fish (fed continuously except 24 hr prior to injections) in 10 microliters of saline/g body weight; final hormone dose was 100 ng/g body weight. Tissue and plasma were sampled 1 and 3 hr after injection. Insulin resulted in depressed plasma FA concentration and reduced hepatic triacylglycerol lipase activity. In vitro effects of hormones were evaluated by incubating liver and adipose tissue pieces in Hanks-MEM. Glucagon (bovine/porcine) directly stimulated lipid breakdown in both liver and adipose tissue. These actions were manifested by enhanced FA and glycerol released into the culture medium and by elevated triacylglycerol lipase activity. Insulin (bovine) generally appeared antilipolytic as this agent inhibited glucagon-stimulated lipase activity and glucagon-stimulated FA release. Furthermore, insulin (in the presence of glucose) reduced net lipolysis, as indicated by glycerol release, compared to control cultures. These results indicate that nutritional state and glucose are important modulators of lipid mobilization and that glucagon and insulin act directly on lipid storage sites to coordinate lipolysis in rainbow trout.

Somatostatin signaling and the regulation of growth and metabolism in fish

The study of the somatostatins (SS) signaling system in fish has provided important information about the structure, function, and evolution of SSs and their receptors. The SS signaling system elicits widespread biological actions via multiple hormone variants, numerous receptor subtypes, and a variety of signal transduction pathways. SSs alter growth via both direct and indirect actions, including inhibiting growth hormone release at the pituitary, decreasing hepatic GH sensitivity, and lowering plasma IGF-I levels. Metabolism also is significantly influenced by SSs. SSs stimulate the breakdown of energy stores and influences digestion, food intake, nutrient absorption, and food conversion both directly and through the modulation of other hormonal systems. The study of fish, which display a diversity of habitat types and life history forms, reveals that the SS signaling system helps regulate energy partitioning and integrate metabolism with growth and other biological processes.