Liver Protein Metabolism Research Articles

Exploring the relationship between dietary rapeseed meal, condensed tannin and growth, nutrive metabolism in largemouth bass (Micropterus salmoides)

This study evaluated the effects of rapeseed meal (RM) and condensed tannin (CT) on the growth and nutritional metabolism of largemouth bass (Micropterus salmoides), and speculated whether there was interaction between anti-nutritional factors in RM. Eight diets were formulated for 55-day feeding trial, six of which were practical diet groups, including control group (CG), five RM inclusive groups with graded RM levels of 5% (RM5), 10% (RM10), 15% (RM15), 20% (RM20) and 25% (RM25) partially replacing fishmeal, and the other two were semi-purified diets with 0.062% CT (CT5) ≈ the CT content in the RM5 and 0.31% CT (CT25) ≈ the CT content in the RM25. The results of the experiments on replacing fishmeal with RM demonstrated that with the increase of RM substitution level, the weight gain rate (WGR), survival rate (SR) and specific growth rate (SGR) of largemouth bass showed a downward trend. High levels of RM led to the inhibition of digestive enzyme activity in largemouth bass, as well as the manifestation of abnormal markers related to protein, fat, and carbohydrate metabolism in both plasma and liver. RM reduced muscle protein and fat content, although the effect was not statistically significant at 5% RM level. The results of CT concentration experiments showed that the addition of 0.31% CT significantly reduced WGR, SGR, SR, protein efficiency ratio (PER) and gastrointestinal digestive enzyme activity, and significantly increased the feed coefficient ratio (FCR), plasma ammonia (PA), plasma glucose (PG), and hepatic glycogen (HG) and liver triglyceride (TG). The addition of 0.062% CT significantly reduced PG and HG. Supplementation of CT significantly reduced muscle fat. Among the groups of CT supplementation and RM, CT5 exhibited superior WGR, PER and FCR compared to RM5, along with enhanced intestinal trypsin, amylase activity, liver glutamic pyruvic transaminase (GPT) activity and decreased content of HG and liver TG; CT25 exhibited decreased activities of gastric lipase (LPS), enteric trypsin and pepsin, and increased content of total cholesterol (T-CHO) and glucose in plasma in compariosn to RM25, accompanied with no significant change in growth performance. Therefore, largemouth bass exhibited tolerance to a 5% inclusion of RM in the feed without compromising their growth, digestion and metabolic functions. The incorporation of 5% RM, equivalent to a supplemental 0.062% CT, had regulatory effects on the digestion and metabolism of largemouth bass while improving feed utilization. There was an interaction among anti-nutritional factors in RM, with synergistic effect being evident at low RM levels, whereas antagonism more promient at high levels of RM.

The Effects of Glutamine Supplementation on Liver Inflammatory Response and Protein Metabolism in Muscle of Lipopolysaccharide-Challenged Broilers

The aim of our present study was to investigate the effects of Gln supplementation on liver inflammatory responses as well as protein synthesis and degradation in the muscle of LPS-challenged broilers. A total of 120 one-day-old male broiler chickens (Arbor Acres Plus) were randomly arranged in a 2 × 2 factorial design with five replicates per treatment and six broilers per replicate, containing two main factors: immune challenge (injected with LPS in a dose of 0 or 500 µg/kg of body weight) and dietary treatments (supplemented with 1.22% alanine or 1% Gln). After feeding with an alanine or Gln diet for 15 days, broilers were administrated an LPS or a saline injection at 16 and 21 days. The results showed that Gln supplementation alleviated the increased mRNA expressions of interleukin-6, interleukin-1β, and tumor necrosis factor-α induced by LPS in liver. Moreover, the increased activity of aspartate aminotransferase combined with the decreased expression of glutaminase in muscle were observed following Gln addition. In addition, in comparison with the saline treatment, LPS challenge altered the signaling molecules’ mRNA expressions associated with protein synthesis and degradation. However, Gln supplementation reversed the negative effects on protein synthesis and degradation in muscle of LPS-challenged broilers. Taken together, Gln supplementation had beneficial effects: alleviating inflammatory responses, promoting protein synthesis, and inhibiting protein degradation of LPS-challenged broilers.

PSI-21 The Role of N-Carbamylglutamate Supplementation During Last Third of Gestation in Nutrient Restricted Twin-Bearing Ewes

Abstract Nutrient restriction in sheep during pregnancy normally occurs in Patagonia with negative effects on ewe body condition (BCS) and reproductive performance. N-carbamylglutamate (NCG), an analogue of N-acetylglutamate, is postulated to improve urea recycling, nitrogen utilization and antioxidant capacity in ruminants. The objective of this study was to evaluate the effect of oral NCG supplementation in naturally nutrient restricted grazing twin-bearing ewes, on maternal body weight (BW) and body condition score (BCS), serum biochemical indexes and antioxidant capacity in mid-late gestation. Ten twin-bearing ewes were orally dosed once-daily with 60 mg/kg BW NCG in a water carrier from 100 to 140 days of gestation (dg) and were compared with unsupplemented controls (CON; n = 8). Maternal BW, and BCS were recorded every 10 days, from 100 to 140 dg. Blood samples were collected at the same time points to evaluate plasma metabolites (NEFA, urea, total protein, albumin, globulin, Ca, P, Mg, Cholesterol, ASAT, CK, GGT, GLDH, total bilirubin and triglycerides), antioxidant status [malondialdehyde (MDA)], and total antioxidant capacity (TAC). Ewes were managed as a single mob in a paddock with natural pasture (3.3% CP, 1.9 Mcal/kg ME), supplemented with alfalfa hay (600 g· ewe-1· /day-1; 13% CP and ME 2.2 Mcal/kg ME) from 130 dg, with a stocking rate of 0.9 ewes per hectare and a dry matter availability of 525 kg per hectare, representative of Patagonian prairie conditions. The effect of treatment on ewe BW, BCS and plasma metabolites were analyzed using REML analysis in R using lme4 R package with time (dg) and treatment (and their interaction) as fixed effects and animal as the random effect. Ewe BW increased (P < 0.0001) and BCS decreased (P = 0.005) with advancing gestation, but there was no effect of treatment. There was a tendency for a treatment effect (P = 0.07) on plasma urea with ~10% less concentrations in NCG than CON ewes at 130 dg (P = 0.08) and 140 dg (P = 0.04). There was a treatment by time interaction for total bilirubin (P = 0.005), phosphorus (P = 0.02), and a similar trend for albumin (P = 0.09). Ewes supplemented with NCG had~10% lower concentrations of bilirubin at 100 (P = 0.01) and 120 dg (P = 0.04), less concentrations of phosphorus (P = 0.003) and albumin (P = 0.02) at 140 dg compared with CON ewes. No other effects of treatment on blood metabolites or antioxidant status or capacity were observed. Collectively these results suggest that supplementation of nutritionally restricted ewes with 60 mg/kg BW from 100 to 140 dg did not influence BW or LWT but may have some effects on liver function, protein metabolism, urea recycling, feed intake and/or feed efficiency which warrant further investigation.*Funded by FONDECYT Project N°1221042; AgResearch Strategic Science Investment Fund.

Negative effects of aflatoxin B1 (AFB1) in the diet on growth performance, protein and lipid metabolism, and liver health of juvenile hybrid grouper (Epinephelus fuscoguttatus♀×Epinephelus lanceolatus♂)

With the increasing consumption of plant-based ingredients in aquafeeds, aflatoxin B1 (AFB1) contamination has become an issue of concern. This experiment aimed to investigate the effect of dietary AFB1 levels on the growth and liver function of hybrid grouper and the mechanisms involved. Six diets with different AFB1 levels were formulated at concentrations of 0 μgkg−1 (AFB0), seven μgkg−1 (AFB7), 30 μgkg−1 (AFB30), 111 μgkg−1 (AFB111), 445 μgkg−1 (AFB445) and 2230 μgkg−1 (AFB2230). A total of 540 healthy hybrid grouper with an initial weight of 11.59 ± 0.03 g were selected and randomly divided into six groups of three replicates of 30 fish each for a trial period of eight weeks. The results showed that with increasing dietary AFB1 levels, growth performance decreased, feed conversion ratio increased, and serum liver damage indicators increased. Liver section results also showed a significant hepatic inflammatory response and increased liver ROS levels in the high AFB1 dietary dose group. In addition, combined with the expression of critical genes in the liver, it was shown that high dietary AFB1 levels disrupted normal liver lipid and protein metabolism, reduced liver antioxidant capacity, and upregulated liver inflammation-related gene expression.

Effect of Dangfei Liganning capsule on liver X receptor α/steroid regulatory element binding protein-1/fatty acid synthase signal pathway in rats with metabolic- associated fatty liver disease.

To study the mechanism of Dangfei Liganning capsule in the treatment of rats with metabolic associated fatty liver disease (MAFLD). Totally 48 specific pathogen free Sprague-Dawley male rats were randomly divided into normal Group, model group, Dangfei Liganning high, moderate, and low-dose groups and Essentiale group which were fed with high fat diet for 8 weeks, and gavage and molding were carried out simultaneously. Dangfei Liganning high, middle and low-dose group were given 0.27, 0.135 and 0.0675 g·kg·d respectively by gavage, Essentiale group was given 0.123 g·kg·d by gavage, the same amount of distilled water was given by gavage in the normal group and the model group. The rats were weighed at the 0th week, 2nd week, 4th week, 6th week and 8th weekend respectively. The rats were sacrificed at the end of the 8th week. Serum levels of alanine aminotransferase (ALT), alanine aminotransferase (AST), triglyceride (TG), total cholesterol (CHO), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein (LDL-C), total protein (TP), albumin (Alb), globulin (GLB), total bilirubin (TBIL), direct bilirubin (DBIL), tumor necrosis factor-α(TNF-α) and interleukin-6 (IL-6) were measured. The levels of liver tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and liver pathology [hematoxylin and eosin (HE) staining, oil red O staining] were detected. The expression levels of liver X receptor α (LXRα), steroid regulatory element binding protein-1 (SREBP-1) and fatty acid synthase (FAS) were detected by immunohistochemistry, Western blot and reverse transcription-polymerase chain reaction reverse transcription-polymerase chain reaction. From the beginning to the 8th week, the growth rate of body weight in the Dangfei Liganning high-dose group was slower than all other groups. There was no significant difference in ALB level in all groups ( 0.05). Compared with the model group, the levels of ALT, AST, LDL-C, TG, CHO, TP, GLB, TBIL, DBIL, IL-6, TNF-α were significantly decreased and HDL-C were significantly increased in Dangfei Liganning high-dose group (0.01, < 0.05). HE and oil red O staining showed that the fatty lesions in rat liver were alleviated, while the expressions of LXRα, SREBP-1, FAS mRNA and protein were significantly decreased (0.01). Dangfei Liganning capsule can slow down the increase of body weight of MAFLD rats, reduce the levels of transaminase, Lipid and inflammatory factors in MAFLD rats, promote the synthesis of liver protein and bile metabolism, and improve the liver fatty lesion of MAFLD rats, among which the Dangfei Liganning high-dose group is more effective. The mechanism of action may be through blocking LXR-SREBP-1-FAS signal pathway.

Replacement of dietary fish meal with Clostridium autoethanogenum meal on growth performance, intestinal amino acids transporters, protein metabolism and hepatic lipid metabolism of juvenile turbot (Scophthalmus maximus L.)

Clostridium autoethanogenum meal (CAM) is a novel single-cell protein, which is produced from bacteria using carbon monoxide (CO) as sole carbon source. To evaluate the efficiency of CAM as an alternative for dietary fish meal, a 56-days growth experiment was performed on juvenile turbot (Scophthalmus maximus L.) with initial average weight of 9.13 ± 0.02 g. Six iso-nitrogenous (crude protein, 51.0%) and iso-lipidic (crude lipid, 11.5%) diets were formulated with 0%, 15%, 30%, 45%, 60% and 80% dietary fish meal protein substituted by CAM protein, which were designated as CAM0 (the control group), CAM15, CAM30, CAM45, CAM60 and CAM80, respectively. Results showed that no significant differences were observed in survival rate (over 97.50%) among different dietary treatments (p > 0.05). The specific growth rate (SGR) was not significantly affected when replacement levels of dietary fish meal with CAM were less than 45% (p > 0.05). The feed intake (FI) was significantly linear reduced with increasing dietary CAM (p < 0.05), whereas no significant differences were observed in feed efficiency ratio (FER), protein efficiency ratio (PER) and protein retention (PR) among different dietary treatments (p > 0.05). With increasing dietary CAM, lipid retention (LR) and carcass lipid tended to be increased in both significantly linear and quadratic patterns (p < 0.05). The apparent digestibility coefficient (ADC) of crude protein and some essential amino acids, including threonine, valine, lysine, histidine and arginine, showed significantly linear increase with increasing dietary CAM (p < 0.05). Furthermore, with the increase of dietary CAM, the gene expression of intestinal peptide and amino acids transporters was first up-regulated and then down-regulated with significantly quadratic pattern (p < 0.05), peaking in fish fed with diets CAM30 or CAM45, which was similar to the expression of genes related protein degradation in muscle. For genes related to protein metabolism in liver and muscle, the expression of mammalian target of rapamycin (mtor) was not significantly affected by dietary CAM, while the general control nonderepressible 2 (gcn2) tended to be first up-regulated and then down-regulated with significantly quadratic pattern (p < 0.05). Apart from that, the lipid metabolism of turbot was also affected by high dietary CAM, evidenced by increased expression of hepatic genes related to lipogenesis as well as reduced expression of genes related to lipid oxidation and lipid transport. In conclusion, CAM can replace up to 45% fish meal protein in diet for juvenile turbot without significantly adverse effects on growth performance. But excessive dietary CAM would result in significant growth reduction, and excessive lipid deposition may also occur in fish fed diets with high levels of CAM.

MitoPlex: A targeted multiple reaction monitoring assay for quantification of a curated set of mitochondrial proteins

Mitochondria are the major source of cellular energy (ATP), as well as critical mediators of widespread functions such as cellular redox balance, apoptosis, and metabolic flux. The organelles play an especially important role in the maintenance of cardiac homeostasis; their inability to generate ATP following impairment due to ischemic damage has been directly linked to organ failure. Methods to quantify mitochondrial content are limited to low throughput immunoassays, measurement of mitochondrial DNA, or relative quantification by untargeted mass spectrometry. Here, we present a high throughput, reproducible and quantitative mass spectrometry multiple reaction monitoring based assay of 37 proteins critical to central carbon chain metabolism and overall mitochondrial function termed ‘MitoPlex’. We coupled this protein multiplex with a parallel analysis of the central carbon chain metabolites (219 metabolite assay) extracted in tandem from the same sample, be it cells or tissue. In tests of its biological applicability in cells and tissues, “MitoPlex plus metabolites” indicated profound effects of HMG-CoA Reductase inhibition (e.g., statin treatment) on mitochondria of i) differentiating C2C12 skeletal myoblasts, as well as a clear opposite trend of statins to promote mitochondrial protein expression and metabolism in heart and liver, while suppressing mitochondrial protein and ii) aspects of metabolism in the skeletal muscle obtained from C57Bl6 mice. Our results not only reveal new insights into the metabolic effect of statins in skeletal muscle, but present a new high throughput, reliable MS-based tool to study mitochondrial dynamics in both cell culture and in vivo models.

Molecular Docking and Preclinical Study of Five-Membered S,S-Palladaheterocycle as Hepatoprotective Agent.

Purpose: In order to investigate mechanisms underlying the hepatoprotective action of S,Spalladaheterocycle, inhibition of cytochromes P450 has been modeled by molecular docking of four palladaheterocycle stereoisomers to the active sites of an enzymatic oxidase system. To obtain a deeper insight into biochemical aspects providing a basis for the therapeutic effects of five-membered palladacycles (as mixture of stereoisomers), a number of preclinical trials has been conducted Methods: 2D and 3D structures of palladaheterocycle stereoisomers were obtained via converting into SDF files by means of software MarvinSketch. Binding of palladaheterocycle at the active sites of cytochromes P450 2E1 and P450 2C9 has been studied by molecular docking using LeadIT 2.3.2. Hepatoprotective activity of palladaheterocycle at 2.5, 25 and 250 mg/kg doses has been studied based on a model of acute intoxication by CCl4 using in vivo methods. Results: By molecular docking it was identify amino acid fragments responsible for binding with palladacyclic isomers. The tested compound is comparable, in terms of its activity to the hepatoprotective drug SAM according to the in vivo and in vitro experiments such as animal survival data, the efficiency of correction of the cytolytic syndrome, the liver excretory function, carbohydrate, protein and lipid metabolism, and the correction efficiency of the liver antitoxic function (the latter has been determined based on the results of a hexobarbital control experiment). Conclusion: Taking into account results obtained in vivo, in vitro and in silico, it can be concluded that the five-membered S,S-palladaheterocycle effectively protect the liver against acute damage caused by CCl4 , via activation of catalase and glucuronyltransferase, as well as via inhibition of the oxidative stress enzymes.

Effect of Nickel Supplementation on Liver and Kidney Function Test and Protein Metabolism in Growing Cattle

This study was conducted to assess the nickel (Ni) content of commonly available feedstuffs and their supplemental effect on biomarkers of liver and kidney function and protein metabolism in growing cattle. Eighteen growing Hariana heifers were randomly assigned to three groups for 90 days and managed on similar feeding regimen except that these three groups were supplemented with 0.0 (Ni0.0), 1.5 (Ni1.5), and 3.0 (Ni3.0) of Ni/kg DMI. Cereal grain by-products, cakes and meals, green fodders, molasses, and compounded concentrate were high in Ni content. Cereal grains, straw, and stovers were moderate to low in Ni content. Dietary supplementation of 3.0 mg of Ni/kg DMI showed linear increase (P < 0.01) in average daily gain. No effects of treatments were observed on haemoglobin concentration, haematocrit value, aspartate aminotransferase level, alanine aminotransferase level, and alkaline phosphatase level. Circulating levels of bilirubin (P < 0.05) and creatinine (P < 0.01) showed dose-dependent increase with supplemental Ni. Heifers receiving diet supplemented with Ni showed higher (P < 0.001) plasma urease activity, plasma levels of total protein, albumin, globulin, and plasma urea nitrogen as compared to non-supplemented heifers. Ni supplementation showed a trend of linear increase (P < 0.001) in plasma Ni concentrations, and Ni level was observed highest in Ni3.0 group. Mean plasma iron (Fe) concentration showed no effect of Ni supplementation. The results of the present study indicate that Ni supplementation seems to improve performance in growing cattle by modulating urease activity and protein metabolism.

Quantitative proteomics reveals systematic dysregulations of liver protein metabolism in sucralose-treated mice

Sucralose, one kind of “sugar-free” artificial sweeteners, is widely used as food and drinks additives. It is generally considered that sucralose is safe because majority of ingested sucralose is not metabolized and absorbed by human body. However, increasing evidence shows the negative effects of artificial sweeteners in perturbations of gut microbiota which plays an important role in a variety of processes related to host health such as immune system development. Specifically, sucralose uptake can alter the homeostasis of mouse gut microbiota, resulting in the significant changes of gut bacterial genera diversity, metabolic patterns, and fecal metabolite profiles as well as inducing host liver inflammation. Therefore, there is a need to study liver proteome changes which may be potentially affected by sucralose-induced dysbiosis. In this study, isobaric labeling-based quantitative proteomics was performed to reveal the liver functional proteome changes in male C57BL/6J mice with sucralose administration in drinking water for six-month period. The labeled tryptic peptides were off-line fractionated before LC-MS/MS analysis to improve proteome coverage detected. SignificanceWe demonstrated the first quantitative proteomics for mice liver proteome to evaluate the effect of sucralose consumption. In total, >5700 protein groups were identified from 18 mouse liver tissues (9 from control group; 9 from sucralose-treated group), and 4327 protein groups were quantified in all samples without any missing values. Among them, 113 protein groups were identified with statistical significance (q value <0.05) as differentially expressed proteins. Bioinformatics analysis revealed the systematic dysregulations of protein metabolism after sucralose treatment. Importantly, our findings proposed that enhanced inflammation may be triggered by ribosomal inactivation in sucralose treated mice liver.

Relationship between the state coagulation system, protein and fat metabolism, and Brain iron deposition in patients with cerebral small vessel disease

Brain iron deposition correlates with clinical manifestations of cerebral small vessel disease. Excessive iron load leads to the formation of free radicals, and nervous tissue damage. The main damaging effect of hydroxyl radicals is due to conversion of soluble fibrinogen to insoluble fibrin. There is also a possible relationship between the functional state of the liver and the early manifestations of cardiovascular disease. Objective: to investigate the relationship between the parameters of coagulation system, liver functional state, fat and protein metabolism, and brain iron deposition in patients with cerebral small vessel disease in the presence of hypertension and cerebral atherosclerosis. Materials and methods: 80 patients with diagnosed cerebral small vessel disease were selected. Patients were divided into two groups, depending on the severity of brain iron deposition. All patients underwent MRI in the T1-WI, T2-WI, TIRM, DWI, and SWI sequences. Determination of the coagulation system parameters and the biochemical analysis were carried out during routine blood test. Results: using a double-sample t test, it was determined that patients with severe brain iron deposition had higher levels of urea, triglycerides, and prolonged thrombin time. With the logistic regression analysis adjusted by the age and sex, levels of urea and the length of thrombin time were determined as the independent risk factors for severe brain iron deposition. For urea OR 1.87, CI 95% 1.31-2.65 (p = 0.02), for thrombin time OR 1.55, CI 95% 1.06-2.26 (p = 0.02). For these parameters, the risk increased when assessing only patients with ALT levels&gt; 15 U / l. For such patients, the relationship between thrombin time and brain iron deposition increased significantly: OR 2.11, CI 95% 1.20-3.71 (p = 0.01). In this study no relationship was found between the indicators of fat metabolism, levels of fibrin and iron deposition. There is a probable relationship between the brain iron deposition and the state of coagulation system, protein metabolism and liver functional state in patients with cerebral small vessel disease.

Dietary Methionine Restriction Upregulates Endogenous H2 S via miR-328-3p: A Potential Mechanism to Improve Liver Protein Metabolism Efficiency in a Mouse Model of High-fat-diet-induced Obesity.

Dietary methionine restriction (MR) promotes multifaceted health benefits. Moreover, lower rate of protein synthesis by dietary MR is associated with life span extension. The goal of this work is to explore how dietary MR would affect protein metabolism in a mouse model of high-fat-diet-induced obesity (DIO). DIO mice (male C57BL/6) are subjected to dietary MR for 22weeks. High-throughput sequencing technology, qRT-PCR analysis, and the dual luciferase reporter assay are performed to verify that MiR-328-3p directly targets cystathionine γ-lyase (CSE) to modulate endogenous H2 S production. Moreover, indicators of endogenous H2 S, fractional synthesis rate (FSR), fractional growth rate (FGR), fractional degradation rate (FDR), and protein retention efficiency (PRE) are analyzed. MR results in an increase in endogenous H2 S to relieve oxidative stress and ER stress to improve protein homeostasis and metabolic efficiency in DIO mice. Results show that dietary MR increases endogenous H2 S production via miR-328-3p. Furthermore, these results suggest the potential involvement of endogenous H2 S on the efficiency of protein metabolism in dietary MR.

Antimicrobial promotion of pig growth is associated with tissue-specific remodeling of bile acid signature and signaling

The spread of bacterial resistance to antimicrobials (AMA) have intensified efforts to discontinue the non-therapeutic use of AMA in animal production. Finding alternatives to AMA, however, is currently encumbered by the obscure mechanism that underlies their growth-promoting action. In this report, we demonstrate that combinations of antibiotics and zinc oxide at doses commonly used for stimulating growth or preventing post-weaning enteritis in pigs converge in promoting microbial production of bile acids (BA) in the intestine. This leads to tissue-specific modifications in the proportion of BA, thereby amplifying BA signaling in intestine, liver, and white adipose tissue (WAT). Activation of BA-regulated pathways ultimately reinforces the intestinal protection against bacterial infection and pathological secretion of fluids and electrolytes, attenuates inflammation in colon and WAT, alters protein and lipid metabolism in liver, and increases the circulating levels of the hormone FGF19. Conceivably, these alterations could spare nutrients for growth and improve the metabolic efficiency of AMA-treated animals. This work provides evidence that BA act as signaling molecules that mediate host physiological, metabolic, and immune responses to the AMA-induced alterations in gut microbial metabolism, eventually permitting the growth-promoting action of AMA. Consequently, BA emerge as a promising target for developing efficacious alternatives to AMA.

Evaluation of biological effectiveness of amino acid mixture as potential stimulator of synthetic processes in skeletal muscles

Background. The ability of certain amino acids to stimulate anabolic processes in skeletal muscles has been proved by fundamental research, which makes it important to search for effective agents based on amino acids for stimulation of synthetic processes in skeletal muscles.&#x0D; Aim. To study the effect of oral administration of the original amino acid mixture (Larginine, Lmethionine, Lleucine, Lisoleucine) on protein, lipid and carbohydrate metabolism in skeletal muscles and liver of CBA male mice.&#x0D; Material and Methods. Two series of experiments were performed. In the first series (n=36), the animals were divided into three groups. In group 1 (n = 12), the mice received a diet balanced in protein and carbohydrates for two months. The animals of group 2 (n=12) were kept on a carbohydrate, proteindepleted isocaloric diet, in which wheat gliadin served as the protein source. Mice of group 3 (n=12) were kept on a diet similar to the second group, in which deficit of protein was compensated for with the tested mixture of Lamino acids. In the animals of the second series (n=36) acute liver failure was modeled by a single intraperitoneal injection of 20% carbon tetrachloride solution (CTC) in olive oil. Three days after the injection of CTC, all animals of the second series were randomly divided into three groups, depending on the received diet.&#x0D; Results. The results of the first series of experiments showed that compensation for protein deficiency with amino acid mixture reliably prevented excessive buildup of glycogen in muscles, led to a decrease in lipids in tissue, and also prevented reduction in the level of muscle protein. The results of the second series of experiments showed that intake of the amino acid mixture prevented loss of protein in muscles and supported the proteinsynthetic function of the liver.&#x0D; Conclusion. The study demonstrated that the tested mixture, when taken orally, can prevent disorders of proteincarbohydratelipid ratio in the muscles.

Evaluation of biological effectiveness of amino acid mixture as potential stimulator of synthetic processes in skeletal muscles

Background. The ability of certain amino acids to stimulate anabolic processes in skeletal muscles has been proved by fundamental research, which makes it important to search for effective agents based on amino acids for stimulation of synthetic processes in skeletal muscles.&#x0D; Aim. To study the effect of oral administration of the original amino acid mixture (Larginine, Lmethionine, Lleucine, Lisoleucine) on protein, lipid and carbohydrate metabolism in skeletal muscles and liver of CBA male mice.&#x0D; Material and Methods. Two series of experiments were performed. In the first series (n=36), the animals were divided into three groups. In group 1 (n = 12), the mice received a diet balanced in protein and carbohydrates for two months. The animals of group 2 (n=12) were kept on a carbohydrate, proteindepleted isocaloric diet, in which wheat gliadin served as the protein source. Mice of group 3 (n=12) were kept on a diet similar to the second group, in which deficit of protein was compensated for with the tested mixture of Lamino acids. In the animals of the second series (n=36) acute liver failure was modeled by a single intraperitoneal injection of 20% carbon tetrachloride solution (CTC) in olive oil. Three days after the injection of CTC, all animals of the second series were randomly divided into three groups, depending on the received diet.&#x0D; Results. The results of the first series of experiments showed that compensation for protein deficiency with amino acid mixture reliably prevented excessive buildup of glycogen in muscles, led to a decrease in lipids in tissue, and also prevented reduction in the level of muscle protein. The results of the second series of experiments showed that intake of the amino acid mixture prevented loss of protein in muscles and supported the proteinsynthetic function of the liver.&#x0D; Conclusion. The study demonstrated that the tested mixture, when taken orally, can prevent disorders of proteincarbohydratelipid ratio in the muscles.

DIABETES MELLITUS IN PATIENTS WITH LIVER CIRRHOSIS: NEW TREATMENT OPTIONS

In economically developed countries, cirrhosis is one of the six leading causes of death at the age of 35–60 years and ranges from 14 to 30 cases per 100000 population. In the world 40 million people die of cirrhosis each year. At 6% of the population of the Russian Federation there is a diabetes mellitus. The combination of diabetes mellitus in patients with cirrhosis of the liver is a common comorbid pathology. Diabetes mellitusis a risk factor for the development of liver cirrhosis, and the incidence of combination of both diseases is quite high, although the frequency of occurrence varies. About 80% of patients with LC may have impaired glucose metabolism, and 30% have diabetes mellitus. Prospective studies have shown that diabetes is associated with an increased risk of developing hepatic complications and death in patients with cirrhosis of the liver. Diabetes mellitus increases the risk of complications of liver cirrhosis of any etiology (varicose veins of the esophagus, hepatic encephalopathy, hepatic-cell insufficiency) and subsequent survival. The incidence, frequency of hospitalizations and mortality from this combined pathology are very high. There are common mechanisms that provoke metabolic and autoimmune disorders in the development of chronic hepatitis and cirrhosis, leading to steatosis, insulin resistance, impaired glucose tolerance and the development of diabetes mellitus. There are certain features of the evaluation of the compensation of carbohydrate metabolism in patients with cirrhosis of the liver, anemia and impaired protein metabolism. Effective control of glycemia can have a beneficial effect on the treatment of these patients. However, few studies have evaluated the efficacy and safety of antidiabetic drugs and the effect of diabetes treatment on morbidity and mortality in patients with cirrhosis. Previously it was believed that in the presence of cirrhosis the only treatment remains insulin. At present, in connection with the emergence of modern groups of hypoglycemic drugs, as well as new approaches to the treatment of type 2 diabetes, this concept has radically changed. Unfortunately, the issues of correction of carbohydrate metabolism in patients with cirrhosis of the liver are practically not covered in the world literature. This article deals with the correction of carbohydrate metabolism in patients with cirrhosis and hepatocellular insufficiency of insulin analogs, biguanides, drugs with incretin effect — dipeptidyl peptidase‑4 inhibitors, agonists of glucagon-like peptide‑1, inhibitors of sodium-glucose cotransporter 2 diabetes. Particular attention is paid to the development of hepatocellular insufficiency and portal hypertension in patients with cirrhosis and type 2 diabetes, as well as processes for their prevention and insulin alternative correction methods.

Glucagon's effect on liver protein metabolism in vivo.

The postprandial state is characterized by a storage of nutrients in the liver, muscle, and adipose tissue for later utilization. In the case of a protein-rich meal, amino acids (AA) stimulate glucagon secretion by the α-cell. The aim of the present study was to determine the impact of the rise in glucagon on AA metabolism, particularly in the liver. We used a conscious catheterized dog model to recreate a postprandial condition using a pancreatic clamp. Portal infusions of glucose, AA, and insulin were used to achieve postprandial levels, while portal glucagon infusion was either maintained at the basal level or increased by three-fold. The high glucagon infusion reduced the increase in arterial AA concentrations compared with the basal glucagon level (-23%, P < 0.05). In the presence of high glucagon, liver AA metabolism shifted toward a more catabolic state with less protein synthesis (-36%) and increased urea production (+52%). Net hepatic glucose uptake was reduced modestly (-35%), and AA were preferentially used in gluconeogenesis, leading to lower glycogen synthesis (-54%). The phosphorylation of AMPK was increased by the high glucagon infusion (+40%), and this could be responsible for increasing the expression of genes related to pathways producing energy and lowering those involved in energy consumption. In conclusion, the rise in glucagon associated with a protein-rich meal promotes a catabolic utilization of AA in the liver, thereby, opposing the storage of AA in proteins.

Effects of dietary soy protein concentrate meal on growth, immunity, enzyme activity and protein metabolism in relation to gene expression in large yellow croaker Larimichthys crocea

A 56-day feeding trial was conducted to investigate the effects of dietary soy protein concentrate meal (SPC) levels on growth performance, body composition, antioxidant and immune responses, enzyme activities and protein metabolism in relation to gene expression in Larimichthys crocea (initial weight 10.50±0.04g). Five isonitrogenous and isolipidic diets (45% protein and 10% lipid) were formulated by replacing 0 (the control), 25%, 50%, 75% and 100% of fish meal protein with SPC protein (designed SPC0, SPC25T, SPC50T, SPC75T and SPC100T, respectively). Lysine and methionine were added to the feed except the control diet, and the levels in the treatment diets were the same. Each diet was randomly fed twice daily (05:00 and 17:00) to apparent satiation to triplicate groups (60 fish per cage). The survival rate (SR) ranged from 90.56 to 93.89%, with no significant differences observed among dietary treatments (P>0.05). In addition, no significant differences were found for weight gain ratios (WGR), specific growth rates (SGR), feed conversion ratios (FCR) and feed intakes (FI) (P>0.05). Fish muscle protein and moisture contents did not show any statistical differences among the dietary treatments (P>0.05). Lipid contents first increased and then decreased, and the SPC25T diet was the highest. Ash contents first decreased and then increased, and the SPC100T diet was the highest. Fish whole-body composition analysis showed that with increasing dietary SPC levels, protein contents did not show any statistical differences among the dietary treatments (P>0.05). Lipid contents were significantly lower of SPC100T than SPC0 and SPC25T diets (P<0.05), and the highest was in the SPC0 diet. The contents of moisture in SPC100T diet were observed the highest, and significantly higher than the control diet (P<0.05). Ash contents of SPC50T diet were significant higher than SPC0 and SPC25T diets (P<0.05), but no significant differences were found among the diets of SPC50T, SPC75T and SPC100T (P>0.05). Significantly lower liver total superoxide dismutase (t-SOD) activity was found for the SPC100T diet than the SPC25T and SPC50T diets (P<0.05). There were no significant differences among the dietary diets with regard to malondialdehyde (MDA), catalase (CAT), and glutathione peroxidase （GPx） (P>0.05). Serum lysozyme (LYZ) activity was significantly lower in the SPC100T diet than in the SPC25T and SPC75T diets (P<0.05). There were no significant differences among the diets for alkaline phosphatase (AKP), complement C3 and C4 (P>0.05). Regarding digestive enzymes, no significant differences were found for hintgut alpha-amylase and lipase activity between the dietary treatments and the control diet (P>0.05). Among all diets, trypsin activity was the highest in fish fed the SPC75 diet, and significantly higher than SPC50T (P<0.05), but there were no significant differences among the SPC0, SPC25T, SPC75T and SPC100T diets (P>0.05). For liver protein metabolism enzymes, no significant differences were found in alanine aminotransferase (ALT) and aspartate amino-transferase (AST) among all dietary diets (P>0. 05). With increasing dietary SPC levels, hepatic insulin-like growth factor-I (IGF-I) expression decreased, and significant differences were observed between SPC50T, SPC75T, SPC100T and the control diets (P<0.05). Target of rapamycin (TOR) expression in the liver decreased, and there were significant differences between the treatment and the control diets (P<0.05).In conclusion, the results of this study suggest that SPC can completely replace fish meal protein as feed for large yellow croaker with no significant negative effects on growth performance.

Potential of processed animal protein versus soybean meal to replace fish meal in practical diets for European catfish (Silurus glanis): growth response and liver gene expression

A 9-week study was conducted to evaluate the potential of processed animal protein (PAP) in comparison with soybean meal (SM) to replace fish meal (FM) in practical diets for European catfish, Silurus glanis, on growth performance, liver transaminase activities and expression of growth-related genes. Seven isonitrogenous (440 g kg-1 crude protein) and isoenergetic (16.70 MJ/kg) practical diets were formulated by replacing 0 (control), 30%, 60% and 100% FM with either SM or PAP. Each diet was randomly assigned to triplicate groups of 25 fish per cages fixed in the pond. Fish fed the diet substituted 100% FM from SM or PAP had lower (p < .05) growth performance, feed efficiency and protein retention compared to control and other groups. The decreased growth performance occurred concomitant with a decline in the expression level of liver GHR/IGF-I axis genes. The gene expression and activity of liver protein metabolism enzymes also positively correlated with growth performance. Findings of this study indicated that both SM and PAP were equally effective in replacing FM up to 60% in the practical diet of Silurus glanis. Total replacement of FM either with SM or PAP induced negative influences on growth and feed utilization.

High Dietary Selenium Intake Alters Lipid Metabolism and Protein Synthesis in Liver and Muscle of Pigs

Background: Prolonged high intakes of dietary selenium have been shown to induce gestational diabetes in rats and hyperinsulinemia in pigs.Objective: Two experiments were conducted to explore metabolic and molecular mechanisms for the diabetogenic potential of high dietary selenium intakes in pigs.Methods: In Expt. 1, 16 Yorkshire-Landrace-Hampshire crossbred pigs (3 wk old, body weight = 7.5 ± 0.81 kg, 50% males and 50% females) were fed a corn-soybean meal basal diet supplemented with 0.3 or 1.0 mg Se/kg (as selenium-enriched yeast for 6 wk). In Expt. 2, 12 pigs of the same crossbreed (6 wk old, body weight = 16.0 ± 1.8 kg) were fed a similar basal diet supplemented with 0.3 or 3.0 mg Se/kg for 11 wk. Biochemical and gene and protein expression profiles of lipid and protein metabolism and selenoproteins in plasma, liver, muscle, and adipose tissues were analyzed.Results: In Expt. 1, the 1-mg-Se/kg diet did not affect body weight or plasma concentrations of glucose and nonesterified fatty acids. In Expt. 2, the 3-mg-Se/kg diet, compared with the 0.3-mg-Se/kg diet, increased (P < 0.05) concentrations of plasma insulin (0.2 compared with 0.4 ng/mL), liver and adipose lipids (41% to 2.4-fold), and liver and muscle protein (10–14%). In liver, the 3-mg-Se/kg diet upregulated (P < 0.05) the expression, activity, or both of key factors related to gluconeogenesis [phosphoenolpyruvate carboxykinase (PEPCK); 13%], lipogenesis [sterol regulatory element binding protein 1 (SREBP1), acetyl-coenzyme A carboxylase (ACC), and fatty acid synthase (FASN); 46–90%], protein synthesis [insulin receptor (INSR), P70 ribosomal protein S6 kinase (P70), and phosphorylated ribosomal protein S6 (P-S6); 88–105%], energy metabolism [AMP-activated protein kinase (AMPK); up to 2.8-fold], and selenoprotein glutathione peroxidase 3 (GPX3; 1.4-fold) and suppressed (P < 0.05) mRNA levels of lipolysis gene cytochrome P450, family 7, subfamily A, polypeptide 1 (CYP7A1; 88%) and selenoprotein gene selenoprotein W1 (SEPW1; 46%). In muscle, the 3-mg-Se/kg diet exerted no effect on the lipid profiles but enhanced (P < 0.05) expression of P-S6 and mammalian target of rapamycin (mTOR; 42–176%; protein synthesis); selenoprotein P (SELP; 40-fold); and tumor suppressor protein 53 (P53) and peroxisome proliferator–activated receptor γ (PPARG; 52–58%; lipogenesis) and suppressed (P < 0.05) expression of INSR (59%; insulin signaling); selenoprotein S (SELS); deiodinases, iodothyronine, type I (DIO1); and thioredoxin reductase 1 (TXNRD1; 50%; selenoproteins); and ACC1 and FASN (35–51%; lipogenesis).Conclusion: Our research showed novel roles, to our best knowledge, and mechanisms of high selenium intakes in regulating the metabolism of protein, along with that of lipid, in a tissue-specific fashion in pigs.