Hepatic Intermediary Metabolism Research Articles

The Efficacy of Intratissue Percutaneous Electrolysis (EPI®) and Nutritional Factors for the Treatment of Induced Tendinopathy in Wistar Rats: Hepatic Intermediary Metabolism Effects.

Achilles tendinopathy (TP) is characterized as the third most common disease of the musculoskeletal system, and occurs in three phases. There is currently no evidence of effective treatment for this medical condition. In this study, the modulatory effects of the minimally invasive technique intratissue percutaneous electrolysis (EPI) and combinations of EPI with four nutritional factors included in the diet, hydroxytyrosol (HT), maslinic acid (MA), glycine, and aspartate (AA), on hepatic intermediary metabolism was examined in Wistar rats with induced tendinopathy at various stages of TP. Results obtained showed that induced tendinopathy produced alterations in the liver intermediary metabolisms of the rats. Regarding carbohydrate metabolism, a reduction in the activity of pro-inflammatory enzymes in the later stages of TP was observed following treatment with EPI alone. Among the combined treatments using nutritional factors with EPI, HT+EPI and AA+EPI had the greatest effect on reducing inflammation in the late stages of TP. In terms of lipid metabolism, the HT+EPI and AA+EPI groups showed a decrease in lipogenesis. In protein metabolism, the HT+EPI group more effectively reduced the inflammatory effects of induced TP. Treatment with EPI combined with nutritional factors might help regulate intermediary metabolism in TP disease and reduce the inflammation process.

Early starvation in European seabass (Dicentrarchus labrax) larvae has no drastic effect on hepatic intermediary metabolism in juveniles.

The present study aims to investigate nutritional programming through early starvation in the European seabass (Dicentrarchus labrax). European seabass larvae were fasted at three different developmental periods for three durations from 60 to 65 dph (F1), 81 to 87 dph (F2), and 123 to 133 dph (F3). Immediate effects were investigated by studying gene expression of npy (neuropeptide Y) and avt (Arginine vasotocin) in the head, while potential long-term effects (i.e., programming) were evaluated on intermediary metabolism later in life (in juveniles). Our findings indicate a direct effect regarding gene expression in the head only for F1, with higher avt mRNA level in fasted larved compared to controls. The early starvation periods had no long-term effect on growth performance (body weight and body length). Regarding intermediary metabolism, we analyzed related key plasma metabolites which reflect the intermediary metabolism: no differences for glucose, triglycerides, and free fatty acids in the plasma were observed in juveniles irrespective of the three early starvation stimuli. As programming is mainly linked to molecular mechanisms, we then studied hepatic mRNA levels for 23 key actors of glucose, lipid, amino acid, and energy metabolism. For many of the metabolic genes, there was no impact of early starvation in juveniles, except for three genes involved in glucose metabolism (glut2-glucose transporter and pk-pyruvate kinase) and lipid metabolism (acly-ATP citrate lyase) which were higher in F2 compared to control. Together, these results highlight that starvation between 81 to 87 dph may have more long-term impact, suggesting the existence of a developmental window for programming by starvation. In conclusion, European seabass appeared to be resilient to early starvation during larvae stages without drastic impacts on intermediary metabolism later in life.

Effect of Nutraceutical Factors on Hepatic Intermediary Metabolism in Wistar Rats with Induced Tendinopathy.

Tendinopathy (TP) is a complex clinical syndrome characterized by local inflammation, pain in the affected area, and loss of performance, preceded by tendon injury. The disease develops in three phases: Inflammatory phase, proliferative phase, and remodeling phase. There are currently no proven treatments for early reversal of this type of injury. However, the metabolic pathways of the transition metabolism, which are necessary for the proper functioning of the organism, are known. These metabolic pathways can be modified by a number of external factors, such as nutritional supplements. In this study, the modulatory effect of four dietary supplements, maslinic acid (MA), hydroxytyrosol (HT), glycine, and aspartate (AA), on hepatic intermediary metabolism was observed in Wistar rats with induced tendinopathy at different stages of the disease. Induced tendinopathy in rats produces alterations in the liver intermediary metabolism. Nutraceutical treatments modify the intermediary metabolism in the different phases of tendinopathy, so AA treatment produced a decrease in carbohydrate metabolism. In lipid metabolism, MA and AA caused a decrease in lipogenesis at the tendinopathy and increased fatty acid oxidation. In protein metabolism, MA treatment increased GDH and AST activity; HT decreased ALT activity; and the AA treatment does not cause any alteration. Use of nutritional supplements of diet could help to regulate the intermediary metabolism in the TP.

Effects of dietary chloroquine on fish growth, hepatic intermediary metabolism, antioxidant and inflammatory responses in turbot

Autophagy is a conserved cellular self-digestion process and is essential for individual growth, cellular metabolism and inflammatory responses. It was responsive to starvation, pathogens infection and environmental stress. However, the information on the regulation of autophagy in fish hepatic intermediary metabolism, antioxidant system, and immune responses were limited. In the present study, turbot with inhibited autophagy flux was built by dietary chloroquine. The hepatic metabolic response, antioxidant enzymes and immune responses were explored. Results showed that dietary chloroquine induced the expression of Beclin 1, SQSTM and LC-3II, and effectively inhibited autophagy flux. Autophagy dysfunction depressed fish growth and feed utilization, while it induced clusters of liver lipid droplets. The genes involved in lipolysis and fatty acid β-oxidation, as well as the lipogenesis-related genes in chloroquine group were depressed. The phosphorylation of AMPK was activated in chloroquine group, and the genes involved in glycolysis were induced. The hepatic content of malonyldialdehyde and the activities of SOD and CAT were induced when autophagy was inhibited. The content of Complement 3, Complement 4 and Immunoglobulin M, as well as the activity of lysozyme in plasma were depressed in chloroquine group. Dietary chloroquine induced the expression of toll-like receptors and stimulated the expression of myd88 and nf-κb p65, as well as the pro-inflammatory cytokines, such as tnf-α and il-1β. The expression of anti-inflammatory cytokine tgf-β was depressed in the chloroquine group. Our results would extend the knowledge on the role of autophagy in teleost and assist in improving fishery production.

Dietary lysine level affects digestive enzyme, amino acid transport and hepatic intermediary metabolism in turbot (Scophthalmus maximus)

Lysine is one of the most important essential amino acids in fish, especially in the feed formulated with high levels of plant ingredients. Lysine restriction always led to growth inhibition and poor feed utilization. However, little information was available on its effects on digestion, absorption, and metabolism response in fish. In the present study, three experimental diets were formulated with three lysine levels, 1.69% (LL group), 3.32% (ML group), and 4.90% (HL group). A 10-week feeding trial was carried out to explore the effects of dietary lysine levels on the digestive enzymes, amino acid transporters, and hepatic intermediary metabolism in turbot (Scophthalmus maximus). As the results showed, the activities of lipase and trypsin in ML group were higher than in other groups. Lysine restriction inhibited the expression levels of peptides and amino acid transporters such as PpeT1, y+LAT2, b0,+AT, and rBAT but significantly induced the expression of CAT1. Meanwhile, lysine deficiency elevated the content of T-CHO and LDL-C in plasma, while a higher HDL-C/LDL-C ratio was observed in ML group. For hepatic intermediary metabolism, the increase of lysine level induced the mRNA expression of G6Pase1 and FBPase, but no differences were observed in the expression of the key regulators in glycolysis pathway, such as GK and PK. Furthermore, an appropriate increase in the level of lysine promoted the genes involved in lipolysis, including PPARα, ACOX1, CPT1A, and LPL. However, no differences were observed in the expression of PPARγ, FAS, SREBP1, and LXR, which were important genes related to lipid synthesis. These results provide clues on the metabolic responses on dietary lysine in teleost.

Estimating pentose phosphate pathway activity from the analysis of hepatic glycogen 13 C-isotopomers derived from [U-13 C]fructose and [U-13 C]glucose.

The pentose phosphate pathway (PPP) is an important component of hepatic intermediary metabolism. Jin et al developed an elegant 13 C-NMR method for measuring hepatic PPP flux by quantifying the distribution of glucose 13 C-isotopomers formed from [U-13 C]glycerol. We demonstrate that this approach can be extended to exogenous [U-13 C]fructose and [U-13 C]glucose precursors by 13 C-NMR analysis of glycogen. Twelve male C57BL/6 mice fed standard chow were provided a 55/45 mixture of fructose and glucose at 30% w/v in the drinking water for 18 wk. On the evening before sacrifice, the fructose component was enriched with 20% [U-13 C]fructose for 6 mice, while the glucose component was enriched with 20% [U-13 C]glucose for the remaining 6 mice. Mice were allowed to feed and drink naturally overnight, and then, euthanized. Livers were freeze-clamped and glycogen was extracted and derivatized for 13 C NMR spectroscopy. Flux of each sugar into the PPP relative to its incorporation into glycogen was quantified from selected 13 C glycogen isotopomer ratios. Both [U-13 C]fructose and [U-13 C]glucose precursors yielded glycogen 13 C-isotopomer distributions that were characteristic of PPP activity. The fraction of [U-13 C]glucose utilized by the PPP relative to its conversion to glycogen via the direct pathway was 14 ± 1%, while that from [U-13 C]fructose relative to its conversion to glycogen via the indirect pathway was significantly lower (10 ± 1%, P = .00032). Hepatic PPP fluxes from both [U-13 C]glucose and [U-13 C]fructose precursors were assessed by 13 C NMR analysis of glycogen 13 C-isotopomers. Glucose-6-phosphate generated via glucokinase and the direct pathway is preferentially utilized by the PPP.

Partially Defatted Tenebrio molitor Larva Meal in Diets for Grow-Out Rainbow Trout, Oncorhynchus mykiss (Walbaum): Effects on Growth Performance, Diet Digestibility and Metabolic Responses.

Simple SummaryThe current developments in the aquaculture sector have highlighted the need to find sustainable ingredients to replace fishmeal as a protein source in fish feeds. The use of insect meals may be a valid option, due to their good nutritional values and low ecological footprint. In this study, we evaluated the effects of a progressive fishmeal substitution with increasing concentrations of a partially defatted yellow mealworm meal in rainbow trout diets. We observed that the total substitution of fishmeal with insect meal is feasible and that there are no negative effects on fish growth or on the digestibility of most nutrients. The activities of hepatic enzymes involved in the amino acid metabolism and lipid synthesis were also evaluated. The enzymatic activities were not negatively influenced by insect meal inclusion in the diets. These results are of practical application for feed manufacturers and farmers, as they support the inclusion of insect meals in fish diets to obtain sustainable feeds that able to support an increase in aquaculture production.Insect meals are good candidates to replace fishmeal as new protein sources in aquafeeds. This study evaluated the effects of fishmeal replacement with different dietary inclusion levels of a partially defatted Tenebrio molitor (L.) larva meal (TM) on rainbow trout (Oncorhynchus mykiss Walbaum) growth, diet digestibility, and hepatic intermediary metabolism. A 154-day growth trial was performed with 252 rainbow trout (78.3 ± 6.24 g) randomly divided into twelve tanks and fed four experimental diets containing increasing levels of TM: 0% (TM0), 25% (TM25), 50% (TM50), and 100% (TM100) of fishmeal substitution, corresponding to TM dietary inclusion levels of 0%, 5%, 10%, and 20%, respectively. A digestibility trial was performed feeding 180 rainbow trout (94.6 ± 7.31 g) with the experimental diets used in the growth trial. The growth parameters were not affected by TM dietary inclusion. Regarding the evaluated apparent digestibility coefficients (ADC), only the ADC of crude protein was affected, showing the following trend: TM0 = TM25 > TM50 > TM100. The activities of key hepatic amino acid catabolic and lipogenic enzymes were not affected by the dietary composition. The results suggest that a partially defatted TM could totally replace fishmeal in commercial rainbow trout diets without negative effects on fish performance.

Social status regulates the hepatic miRNAome in rainbow trout: Implications for posttranscriptional regulation of metabolic pathways.

Juvenile rainbow trout develop social hierarchies when held in dyads, and the development of socially subordinate (SS) and social dominance (SD) phenotypes in this context has been linked to specific changes in the hepatic energy metabolism of all major macronutrients. Following our recently reported finding that transcript abundance of drosha, a key component of the microRNA (miRNA) biogenesis pathway, is increased in paired juvenile rainbow trout irrespective of social status compared to socially isolated (SI) controls, we here determined global changes of the hepatic miRNA pathway genes in detail at the transcript and protein level. Both socially SD and SS rainbow trout exhibited increased Ago2 protein abundance compared to SI rainbow trout, suggesting that hepatic miRNA function is increased in rainbow trout maintained in dyads. Given the well-described differences in hepatic intermediary metabolism between socially SD and SS rainbow trout, and the important role of miRNAs in the posttranscriptional regulation of metabolic pathways, we also identified changes in hepatic miRNA abundance between socially SS and SD rainbow trout using small RNA next generation sequencing. We identified a total of 24 differentially regulated miRNAs, with 15 miRNAs that exhibited increased expression, and 9 miRNAs that exhibited decreased expression in the liver of socially SS trout compared to socially SD trout. To identify potential miRNA-dependent posttranscriptional regulatory pathways important for social status-dependent regulation of hepatic metabolism in rainbow trout, we used an in silico miRNA target prediction and pathway enrichment approach. We identified enrichment for pathways related to metabolism of carbohydrates, lipids and proteins in addition to organelle-specific processes involved in energy metabolism, especially mitochondrial fusion and fission. Select predicted miRNA-mRNA target pairs within these categories were quantitatively analyzed by real-time RT-PCR to validate candidates for future studies that will probe the functional metabolic roles of specific hepatic miRNAs in the development of socially SD and SS metabolic phenotypes.

The effects of intraperitoneal administration of Francisella noatunensis subsp. noatunensis on hepatic intermediary metabolism and indicators of stress in Patagonian blennie Eleginops maclovinus.

Francisellosis is a disease produced by Francisella spp. which affects farmed fish. Eleginops maclovinus specimens can be caught close to salmon farming centers, feeding on un-consumed pellet, making the transmission of pathogens such as Francisella noatunensis possible. The aim of this study was to evaluate the effect of F. noatunensis on liver intermediary metabolism in E. maclovinus. 144 fish were injected intraperitoneally with F. noatunensis at a low dose LD (1 × 101 cells/μL), medium dose MD (1 × 105 cells/μL), high dose HD (1 × 1010 cells/μL), or with culture medium C (control), and sampled at 1, 3, 7, 14, 21 and 28 days post injection (dpi). No mortality was recorded during the experimental period, but there was a marked metabolic response in fish injected with high doses. Metabolites in plasma were lowest in the high bacterial dose. Cortisol levels were highest at day 7 in the high dose and then decreased from day 14 until the end of the study. Liver enzymes showed a similar pattern to plasma metabolites, with decreased enzymatic activity, mostly with the high bacteria dose. PK was the exception, with increased enzymatic activity in a dose-dependent manner over time. Liver metabolites were highly variable, except in the high bacterial dose where variability and total levels decreased significantly. Our results show that fish infection with F. noatunensis induces a clear stress response, especially with at the highest dose, shifting intermediary metabolism towards mobilization of energy and suggesting that E. maclovinus detects experimental infection of F. noatunensis as a stressor, which it is dependent on the bacterial dose.

Effect of dietary starch level on growth, metabolism enzyme and oxidative status of juvenile largemouth bass, Micropterus salmoides

A 60-day feeding trial was conducted to investigate the effect of dietary carbohydrate level on the growth performance, body composition,plasma biochemical indices and antioxidant capacity of largemouth bass, Micropterus salmoides. Six isonitrogenous and isolipidic diets containing graded levels of starch (0%, 5%, 10%, 15%, 20% and 25%) were fed to juvenile largemouth bass. The weight gain (WG), specific growth rate (SGR) and protein efficiency ratio (PER) decreased with increasing dietary starch levels (P < .05), whereas feed conversion ratio (FCR) showed the opposite trend. Feed intake (FI) was found to be not significantly related to the dietary starch levels (P < .05). However, liver lipid, hepatic glycogen and muscle glycogen contents increased significantly with dietary starch levels. There were significant differences in hepatic glucose metabolism enzymes in fish fed diets with different dietary starch levels. The hexokinase (HK), glucokinase (GK), and pyruvate kinase (PK) activities in liver increased significantly as dietary starch levels increased, whereas fructose-1,6-bisphosphatase (FBPase), phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase) activities in liver showed the opposite trend. Moreover, the superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and inducible nitric oxide synthase (iNOS) activities, nitric oxide (NO) concent in liver decreased significantly as dietary starch levels increased, while the malondialdehyde (MDA) contents in liver increased. Results demonstrate that the starch levels may affect growth performance and metabolic changes in hepatic intermediary metabolism, which suggest that starch diets were inefficiently used as an energy source by M.salmoides juveniles.

Effect of dietary arachidonic acid levels on growth performance, fatty acid profiles and lipid metabolism of juvenile yellow catfish (Pelteobagrus fulvidraco)

An 8-week feeding trial was conducted to evaluate the effects of different dietary arachidonic acid (ARA) levels on growth performance, fatty acid composition, hepatic intermediary metabolism and antioxidant responses for juvenile yellow catfish. An ARA-enriched oil was supplemented into the basal diet to formulate six iso-nitrogenous and iso-energetic practical diets containing 0.03% (the control diet), 0.30%, 0.60%, 0.90%, 1.20% and 1.50% of dry weight. Dietary ARA levels were 0.39%, 2.47%, 4.96%, 7.49%, 9.79% and 12.64% total fatty acids, respectively. Triplicate groups of 20 fish (average initial weight is about 1.55±0.01g) were fed to apparent satiation twice daily. The results indicated that fish fed the diets containing 4.96% and 7.49% ARA of total fatty acids have higher final body weight and percent weight gain (PWG) than those fed the other diets. Survival, feed conversion ratio, hepatosomatic index and viscerosomatic index were not significantly influenced by the dietary ARA levels. Fatty acid compositions both in liver and muscle reflected closely those of fatty acid profiles in diets, ARA proportion in liver and muscle significantly increased with dietary ARA levels increasing from 0.39% to 12.64% of total fatty acids, while, EPA proportion in liver significantly decreased with increase of dietary ARA levels. Fish fed the control diet had the highest aspartate aminotransferase (AST) and glucose content in serum among all treatments, and fish fed the 9.79% and 12.64% ARA of total fatty acids had higher malondialdehyde (MDA) content in liver than those fed the other diets. However, the activities of total superoxide dismutase (T-SOD), glutathione peroxidase (GSH-PX) and catalase (CAT) in liver were not significantly influenced by dietary ARA levels. The relative gene expression of accα, g6pd, 6pgd and evovl5 in liver down-regulated significantly with the dietary ARA levels increasing from 0.39% to 12.64% of total fatty acids. The relative gene expression of atgl and hslb in liver down-regulated significantly with the dietary ARA levels increasing from 0.39% to 7.49% of total fatty acids, and then up-regulated as dietary ARA levels increasing from 9.79% to 12.64%. However, relative gene expression of cpt1a and ppara in liver are down-regulated in ARA supplemental groups. These results suggested that dietary moderate ARA levels (4.96% and 7.49% of total fatty acids) could improve growth performance and antioxidant response, and up-regulate or down-regulate relative expression levels of some lipid metabolism-related gene in liver. Two slope broken-line regression analysis of PWG against dietary ARA levels indicated that optimal dietary ARA requirement for juvenile yellow catfish was 6.45% of total fatty acids.

Prebiotics effect on growth performance, hepatic intermediary metabolism, gut microbiota and digestive enzymes of white sea bream (Diplodus sargus)

This study aimed at evaluating the effects of short-chain fructooligosaccharides (scFOS), xylooligosaccharides (XOS) and galactooligosaccharides (GOS) on growth performance, hepatic metabolism, gut microbiota and digestive enzymes activities of white sea bream juveniles. Four diets were formulated: a control diet with fish meal (FM) and plant feedstuffs (PF) (30FM:70PF) and three test diets similar to control but supplemented with 10 g of scFOS, XOS or GOS per kilo diet, which were fed to fish during 12 weeks. Prebiotics had no effect on growth, feed efficiency or gut microbiota. Plasmatic triglycerides were lower in fish fed XOS than FOS and GOS diets. Malic enzyme activity was lower in fish fed XOS than FOS diet. Fish fed XOS diet had lower fatty acid synthetase (FAS), a key lipogenic enzyme and higher alanine aminotransferase activities. Fifteen days after the start of the trial, an enhancement of total alkaline protease, trypsin and lipase activities was observed in fish fed prebiotics, but such effect disappeared at 12 weeks. In conclusion, scFOS, XOS or GOS seem to have limited applicability in white sea bream feed.

Increasing levels of dietary crystalline methionine affect plasma methionine profiles, ammonia excretion, and the expression of genes related to the hepatic intermediary metabolism in rainbow trout (Oncorhynchus mykiss).

Strictly carnivorous fish with high requirements for dietary protein, such as rainbow trout (Oncorhynchus mykiss) are interesting models for studying the role of amino acids as key regulators of intermediary metabolism. Methionine is an essential amino acid for rainbow trout, and works as a signalling factor in different metabolic pathways. The study investigated the effect of increasing dietary methionine intake on the intermediary metabolism in the liver of juvenile rainbow trout. For this purpose, five diets were formulated with increasing methionine levels from 0.60 to 1.29% dry matter. The diets were fed in excess for six weeks before three sampling campaigns carried out successively to elucidate (i) the hepatic expression of selected genes involved in lipid, glucose and amino acid metabolism; (ii) the postprandial ammonia excretion; and (iii) the postprandial plasma methionine concentrations. The transcript levels of enzymes involved in lipid metabolism (fatty acid synthase, glucose 6 phosphate dehydrogenase and carnitine palmitoyl transferase 1 a), gluconeogenesis (fructose-1,6-biphosphatase) and amino acid catabolism (alanine amino transferase and glutamate dehydrogenase) were significantly affected by the increase in dietary methionine. Changes in gene expression reflected to some extent the decrease in ammonia excretion (P=0.022) and in the hepatosomatic index (HSI; P<0.001) when dietary methionine increased. Postprandial plasma methionine concentrations correlated positively with the dietary level (P<0.001) at the different sampling points. The study shows that the expression of several genes related to the hepatic intermediary metabolism in rainbow trout responded in a dose-dependent manner to increasing levels of dietary methionine.

Dietary methionine imbalance alters the transcriptional regulation of genes involved in glucose, lipid and amino acid metabolism in the liver of rainbow trout (Oncorhynchus mykiss)

Supplementation of fish diets with crystalline methionine is needed to overcome the low methionine content of plant based diet and to ensure good growth performances of the farmed fish. The study aimed to investigate the consequences of methionine imbalance on the expression of genes related to hepatic intermediary metabolism in rainbow trout. For this purpose, juvenile trout were fed during 6weeks diets containing either deficient, adequate or excess levels of methionine. The results indicate that the methionine deficiency increased the expression of the activating transcription factor 4 (ATF4) target genes asparagine synthetase (ASNS), system A amino acid transporter 2 (SNAT2) and cationic amino acid transporter 1 (CAT1) as a result of the activation of the GCN2/eIF2α pathway. In contrast, dietary methionine supplied in excess produced broader changes on hepatic gene expression by increasing the levels of transcripts related to fatty acid synthesis (fatty acid synthesis, FAS) and oxidation (hydroxyacyl-CoA dehydrogenase, HOAD), gluconeogenesis (glucose-6-phosphatase 2, G6Pase2 and phosphoénolpyruvate carboxykinase, PEPCK) and amino acid catabolism (glutamate dehydrogenase 1 and 2, GDH 1 and 2). Methionine excess also led to a post-prandial down-regulation of G6Pase2 and PEPCK gene expression not occurring in fish fed the methionine deficient or adequate diet. This study shows that a dietary methionine imbalance in juvenile trout strongly affects hepatic gene expression and that the response highly depends on the nature of the imbalance: deficiency or excess. Statement of relevancePrecise amino acid supplementation of fish diet.

Effects of short-chain fructooligosaccharides (scFOS) and rearing temperature on growth performance and hepatic intermediary metabolism in gilthead sea bream (Sparus aurata) juveniles.

The effect of dietary short-chain fructooligosaccharides (scFOS) incorporation on growth, feed utilization, body composition, plasmatic metabolites and liver activity of key enzymes of lipogenic and amino acid catabolic pathways was evaluated in gilthead sea bream reared at 18 and 25°C. Four practical diets containing plant ingredients and fish meal (50:50) as protein sources and supplemented with 0, 0.1, 0.25 and 0.5% scFOS were fed to triplicate groups of fish for 8weeks. Growth performance, feed efficiency and nitrogen retention were higher at 25°C. In fish reared at 18°C, there was a positive correlation between dietary scFOS concentration and growth. At 18°C, liver glycogen was higher in fish fed the control diet, while at 25°C it was higher in fish fed the 0.5% scFOS diet. Plasma cholesterol LDL was lower in fish fed 0.25% scFOS diet, and in fish reared at 18°C plasma glucose was higher in fish fed the 0.1% scFOS diet. Glucose 6-phosphate dehydrogenase, fatty acid synthetase and aspartate aminotransferase (ASAT) activities were higher in fish reared at 18°C, whereas alanine aminotransferase activity was higher in fish reared at 25°C. scFOS affected ASAT activity, which was lower in fish fed 0.25% scFOS diet. Although, scFOS seemed to have no major effects on gilthead sea bream metabolism, the positive correlation between dietary prebiotic incorporation and growth at 18°C indicates a beneficial effect of scFOS in fish reared at low temperatures.

Dietary fat and hepatic lipogenesis: mitochondrial citrate carrier as a sensor of metabolic changes.

Citrate carrier (CIC) is an integral protein of the inner mitochondrial membrane that has a fundamental role in hepatic intermediary metabolism. Its primary function is to catalyze the transport of citrate from mitochondria, where this molecule is formed, to cytosol, where this molecule is used for fatty acid (FA) and cholesterol synthesis. Therefore, mitochondrial CIC acts upstream of cytosolic lipogenic reactions, and its regulation is particularly important in view of the modulation of hepatic lipogenesis. Although a great deal of data are currently available on the dietary modulation of cytosolic lipogenic enzymes, little is known about the nutritional regulation of CIC transport activity. In this review, we describe the differential effects of distinct FAs present in the diet on the activity of mitochondrial CIC. In particular, polyunsaturated FAs were powerful modulators of the activity of mitochondrial CIC by influencing its expression through transcriptional and posttranscriptional mechanisms. On the contrary, saturated and monounsaturated FAs did not influence mitochondrial CIC activity. Moreover, variations in CIC activity were connected to similar alterations in the metabolic pathways to which the transported citrate is channeled. Therefore, CIC may be considered as a sensor for changes occurring inside the hepatocyte and may represent an important target for the regulation of hepatic lipogenesis. The crucial role of this protein is reinforced by the recent discovery of its involvement in other cellular processes, such as glucose-stimulated insulin secretion, inflammation, tumorigenesis, genome stability, and sperm metabolism.

Effect of fishmeal replacement by soy protein concentrate with taurine supplementation on hepatic intermediary metabolism and antioxidant status of totoaba juveniles (Totoaba macdonaldi)

The effect of dietary incorporation of soy protein concentrate (SPC) and the concomitant supplementation with taurine on hepatic intermediary metabolism and antioxidant status of totoaba (Totoaba macdonaldi) juveniles was assessed. Four isoproteic and isolipidic diets were formulated containing either 30 or 60% of SPC (diets SP30 and SP60), supplemented or not with 1% of taurine (diets SP30T and SP60T). A fish meal (FM) based diet, without SPC and taurine supplementation, was used as a control. Triplicate groups of 32 totoaba juveniles (average body mass=7.5g) were fed these diets over 45days. Results revealed that dietary FM replacement by SPC depressed the overall intermediary metabolism. Activity of key enzymes of amino acid catabolism and gluconeogenesis was significantly reduced and a trend to reduce glycolysis and glucose-6-phosphate dehydrogenase activity was observed. The incorporation of the highest level of SPC also significantly increased hepatic lipid peroxidation and the activity of superoxide dismutase. Concomitant taurine supplementation restored the activity of amino acid catabolic and gluconeogenic enzymes and hexokinase to levels similar of those of the control diet. Taurine supplementation also led to a significant increase of glucose-6-phosphate dehydrogenase and catalase activity, as well as to a significant reduction of liver lipid peroxidation. These results suggest that taurine may play an important metabolic modulation action on totoaba fed SPC based diets, contributing to the enhancement of the overall metabolism and to the reduction of liver oxidative damage.

Hepatic glucose sensing and integrative pathways in the liver.

The hepatic glucose-sensing system is a functional network of enzymes and transcription factors that is critical for the maintenance of energy homeostasis and systemic glycemia. Here we review the recent literature on its components and metabolic actions. Glucokinase (GCK) is generally considered as the initial postprandial glucose-sensing component, which acts as the gatekeeper for hepatic glucose metabolism and provides metabolites that activate the transcription factor carbohydrate response element binding protein (ChREBP). Recently, liver receptor homolog 1 (LRH-1) has emerged as an upstream regulator of the central GCK-ChREBP axis, with a critical role in the integration of hepatic intermediary metabolism in response to glucose. Evidence is also accumulating that O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) and acetylation can act as glucose-sensitive modifications that may contribute to hepatic glucose sensing by targeting regulatory proteins and the epigenome. Further elucidation of the components and functional roles of the hepatic glucose-sensing system may contribute to the future treatment of liver diseases associated with deregulated glucose sensors.

Protective Effects of Calcium Pre-Exposure Against Waterborne Cadmium Toxicity in Synechogobius hasta

The present study was performed to evaluate the effects of calcium (Ca) pre-exposure and then waterborne cadmium (Cd) exposure on metal element accumulation, enzymatic activities, histology, and ultrastructure in Synechogobius hasta and test the hypothesis that Ca could protect against Cd-induced toxicity in the fish species. Three hundred sixty fish [initial mean weight 25.5±0.1g (mean±SEM)] were stocked in 18 circular fiberglass tanks (water volume: 300l), 9 of which were pre-exposed to Ca at a rate of 400mg Ca/l for 9days and then exposed to concentrations of 0, 79.3, and 158.6μg Cd/l for 9days. Another 9 tanks were cultured in natural seawater (no extra Ca addition) for 9days and then exposed to concentrations of 0, 79.3, and 158.6μg Cd/l for 9days. Both Ca pre-exposure and then waterborne Cd exposure influenced the accumulation of metal elements [cadmium (Cd), copper, zinc, and iron] in several tissues (muscle, gill, liver, spleen, and intestine), changed hepatic intermediary metabolism, and induced histological and ultrastructural alterations in tissues. In general, Ca pre-exposure seemed to mitigate the severity of Cd-induced mortality and histopathological injuries indicating that Ca pre-exposure had the capacity to decrease Cd toxicity in S. hasta.

Effect of Dietary Fish Meal Replacement by Canola Meal on Growth Performance and Hepatic Intermediary Metabolism of Genetically Improved Farmed Tilapia Strain of Nile Tilapia, Oreochromis niloticus, Reared in Fresh Water

An 8‐wk feeding trial was conducted to evaluate the potential of replacing fish meal with canola meal in experimental diets for genetically improved farmed tilapia (GIFT) strain of Nile tilapia, Oreochromis niloticus (mean initial weight: 20.0 ± 0.62 g, means ± SD), reared in fresh water. Six isonitrogenous (30% crude protein) and isolipidic (10%) diets were formulated with canola meal included at six levels of 0 (control), 11, 22, 33, 44, and 55%, replacing 0, 15, 30, 45, 60, and 75% fish meal, respectively. Growth performance and feed utilization showed no significant differences among the treatments. In general, dietary canola meal supplementation showed significant effect on hepatic composition of tilapia, but not muscle composition. Viscerosomatic index tended to increase with increasing dietary canola meal levels from 0 to 44%, and then declined when dietary canola meal levels further increased from 44 to 55%. Dietary fish meal replacement by canola meal significantly influenced several hepatic enzymatic activities, including succinate dehydrogenase, lactate dehydrogenase, malic dehydrogenase, lipoprotein lipase, and hepatic lipase, suggesting that dietary fish meal replacement by canola meal had significant effects on nutrient metabolism in the liver. Based on the information above, 75% of dietary fish meal could be replaced by canola meal with no effect on growth performance of GIFT strain of Nile tilapia. Use of canola meal in practical diets for GIFT stain of Nile tilapia may allow producers and feed mills to formulate more economical diets.