Dietary supplementation with inosine-5'-monophosphate improves the functional, energetic, and antioxidant status of liver and muscle growth in pigs.

Inosine 5'-monophosphate (5'-IMP) is an essential nucleotide for de novo nucleotide biosynthesis and metabolism of energy, proteins, and antioxidants. Nucleotides are conditionally essential, as they cannot be produced sufficiently rapidly to meet the needs of the body in situations of oxidative stress or rapid muscle growth. A deficient intake of nucleotides can result in decreased ATP and GTP synthesis and impaired metabolism. We demonstrated that supplementation of finishing pig diets with 5'-IMP reduces the relative weight of the liver, and increases oxygen consumption during mitochondrial respiration without changing the ADP/O ratio, indicating an increase in the respiratory efficiency of liver mitochondria. We also observed a reduction in liver lipid peroxidation and an increase in muscle creatine. Moreover, 5'IMP supplementation increases slaughter weight, lean meat yield, sarcomere length, and backfat thickness in finishing barrows, demonstrating influence on protein metabolism. We suggest that 5'-IMP supplementation increase the mitochondrial respiratory capacity when the liver metabolic activity is stimulated, enhances antioxidant defense, and promotes muscle growth in finishing barrows.

Engineering the Vasculature of Stem-Cell-Derived Liver Organoids.

The vasculature of stem-cell-derived liver organoids can be engineered using methods that recapitulate embryonic liver development. Hepatic organoids with a vascular network offer great application prospects for drug screening, disease modeling, and therapeutics. However, the application of stem cell-derived organoids is hindered by insufficient vascularization and maturation. Here, we review different theories about the origin of hepatic cells and the morphogenesis of hepatic vessels to provide potential approaches for organoid generation. We also review the main protocols for generating vascularized liver organoids from stem cells and consider their potential and limitations in the generation of vascularized liver organoids.

Long-term programming of skeletal muscle and liver lipid and energy metabolism by resveratrol supplementation to suckling mice.

Metabolic programming by dietary chemicals consumed in early life stages is receiving increasing attention. We here studied long-term effects of mild resveratrol (RSV) supplementation during lactation on muscular and hepatic lipid metabolism in adulthood. Newborn male mice received RSV or vehicle from day 2-20 of age, were weaned onto a chow diet on day 21, and were assigned to either a high-fat diet (HFD) or a normal-fat diet on day 90 of age for 10 weeks. RSV-treated mice showed in adulthood protection against HFD-induced triacylglycerol accumulation in skeletal muscle, enhanced muscular capacities for fat oxidation and mitochondria activity, signs of enhanced sirtuin 1 and AMP-dependent protein kinase signaling in muscle, and increased fat oxidation capacities and a decreased capacity for lipogenesis in liver compared with controls. Thus, RSV supplementation in early postnatal life may help preventing later diet-related disorders linked to ectopic lipid accumulation in muscle and liver tissues.

Acute exposure to environmentally relevant concentrations of copper affects branchial and hepatic phosphoryl transfer network of Cichlasoma amazonarum: Impacts on bioenergetics homeostasis.

The toxic effects of copper (Cu) are linked to dysfunction of metabolism and depletion of adenosine triphosphate (ATP). Nevertheless, the effects related to phosphoryl transfer network, a network of enzymes to precise coupling of the ATP-production and ATP-consuming process for maintenance of bioenergetic, remain unknown. Therefore, the aim of this study was to determine whether the phosphoryl transfer network could be one pathway involved in the bioenergetic imbalance of Cichlasoma amazonarum exposed for 96 h to environmentally relevant concentrations of Cu found in Amazonia water around mines. Branchial mitochondrial creatine kinase (CK) activity was significantly lower in fish exposed to 1500 µg/L Cu than in the control group, while branchial cytosolic CK activity was significantly greater. Branchial (exposed to 750 and 1500 µg/L Cu) and hepatic (exposed to 1500 µg/L Cu) pyruvate kinase (PK) activity was significantly lower in fish exposed to Cu than in the control group. Branchial and hepatic ATP levels were significantly lower in fish exposed to 1500 µg/L than in the control group. Branchial reactive oxygen species (ROS) and lipid peroxidation (LPO) levels were significantly higher in fish exposed to 750 and 1500 µg/L Cu compared to control. Hepatic ROS and LPO levels were significantly higher in fish exposed to 1500 µg/L than in the control group. Branchial and hepatic Cu levels were significantly higher in fish exposed to 1500 µg/L compared to other groups. Exposure to 750 and 1500 µg/L Cu impairs bioenergetics homeostasis, which appears to be mediated by ROS overproduction and lipid peroxidation.

Relationship between redox potential of glutathione and DNA methylation level in liver of newborn guinea pigs.

The metabolism of DNA methylation is reported to be sensitive to oxidant molecules or oxidative stress. Hypothesis: early-life oxidative stress characterized by the redox potential of glutathione influences the DNA methylation level. The in vivo study aimed at the impact of modulating redox potential of glutathione on DNA methylation. Newborn guinea pigs received different nutritive modalities for 4 days: oral nutrition, parenteral nutrition including lipid emulsion Intralipid (PN-IL) or SMOFLipid (PN-SF), protected or not from ambient light. Livers were collected for biochemical determinations. Redox potential (p < 0.001) and DNA methylation (p < 0.01) were higher in PN-infused animals and even higher in PN-SF. Their positive correlation was significant (r2 = 0.51; p < 0.001). Methylation activity was higher in PN groups (p < 0.01). Protein levels of DNA methyltransferase (DNMT)-1 were lower in PN groups (p < 0.01) while those of both DNMT3a isoforms were increased (p < 0.01) and significantly correlated with redox potential (r2 > 0.42; p < 0.001). The ratio of SAM (substrate) to SAH (inhibitor) was positively correlated with the redox potential (r2 = 0.36; p < 0.001). In conclusion, early in life, the redox potential value strongly influences the DNA methylation metabolism, resulting in an increase of DNA methylation as a function of increased oxidative stress. These results support the notion that early-life oxidative stress can reprogram the metabolism epigenetically. This study emphasizes once again the importance of improving the quality of parenteral nutrition solutions administered early in life, especially to newborn infants. Abbreviation of Title: Parenteral nutrition and DNA methylation.

Giant Island Mice Exhibit Widespread Gene Expression Changes in Key Metabolic Organs.

Island populations repeatedly evolve extreme body sizes, but the genomic basis of this pattern remains largely unknown. To understand how organisms on islands evolve gigantism, we compared genome-wide patterns of gene expression in Gough Island mice, the largest wild house mice in the world, and mainland mice from the WSB/EiJ wild-derived inbred strain. We used RNA-seq to quantify differential gene expression in three key metabolic organs: gonadal adipose depot, hypothalamus, and liver. Between 4,000 and 8,800 genes were significantly differentially expressed across the evaluated organs, representing between 20% and 50% of detected transcripts, with 20% or more of differentially expressed transcripts in each organ exhibiting expression fold changes of at least 2×. A minimum of 73 candidate genes for extreme size evolution, including Irs1 and Lrp1, were identified by considering differential expression jointly with other data sets: 1) genomic positions of published quantitative trait loci for body weight and growth rate, 2) whole-genome sequencing of 16 wild-caught Gough Island mice that revealed fixed single-nucleotide differences between the strains, and 3) publicly available tissue-specific regulatory elements. Additionally, patterns of differential expression across three time points in the liver revealed that Arid5b potentially regulates hundreds of genes. Functional enrichment analyses pointed to cell cycling, mitochondrial function, signaling pathways, inflammatory response, and nutrient metabolism as potential causes of weight accumulation in Gough Island mice. Collectively, our results indicate that extensive gene regulatory evolution in metabolic organs accompanied the rapid evolution of gigantism during the short time house mice have inhabited Gough Island.

FoxA2 inhibits the proliferation of hepatic progenitor cells by reducing PI3K/Akt/HK2-mediated glycolysis.

FoxA2 is an essential transcription factor for liver organogenesis and homeostasis. Although reduced expression of FoxA2 has been associated with chronic liver diseases, hepatic progenitor cells (HPCs) that are activated in these circumstances express FoxA2. However, the functional effects and underlying mechanism of FoxA2 in HPCs are still unknown. As revealed by immunostaining, HPCs expressed FoxA2 in human cirrhotic livers and in the livers of choline-deficient diet supplemented with ethionine (CDE) rats. Knocking down FoxA2 in HPCs isolated from CDE rats significantly increased cell proliferation and aerobic glycolysis. Moreover, gene transcription, protein expression, and the enzyme activities of hexokinase 2 (HK2) were upregulated, and blocking HK2 activities via 2-deoxyglucose markedly reduced cell proliferation and aerobic glycolysis. Kyoto Encyclopedia of Genes and Genomes analysis revealed that FoxA2 knockdown enhanced the transcription of genes involved in the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) pathway and triggered downstream Akt phosphorylation. Blocking the PI3K/Akt pathway by Ly294002 inhibited HK2 activities, aerobic glycolysis, and cell proliferation in FoxA2-knockdown cells. Therefore, FoxA2 plays an important role in the proliferation and inhibition of HPCs by suppressing PI3K/Akt/HK2-regulated aerobic glycolysis.

Analysis of hiPSCs differentiation toward hepatocyte-like cells upon extended exposition to oncostatin.

The capability to produce and maintain functional human adult hepatocytes remains one of the major challenges for the use of in-vitro models toward liver cell therapy and industrial drug-screening applications. Among the suggested strategies to solve this issue, the use of human-induced pluripotent stem cells (hiPSCs), differentiated toward hepatocyte-like cells (HLCs) is promising. In this work, we propose a 31-day long protocol, that includes a final 14-day long phase of oncostatin treatment, as opposed to a 7-day treatment which led to the formation of a hepatic tissue functional for CYP1A2, CYP2B6, CYP2C8, CYP2D6, and CYP3A4. The production of albumin, as well as bile acid metabolism and transport, were also detected. Transcriptome profile comparisons and liver transcription factors (TFs) motif dynamics revealed increased expression of typical hepatic markers such as HNF1A and of important metabolic markers like PPARA. The performed analysis has allowed for the extraction of potential targets and pathways which would allow enhanced hepatic maturation in-vitro. From this investigation, NRF1 and SP3 appeared as transcription factors of importance. Complex epithelial-mesenchymal transition (EMT) and mesenchymal-epithelial transition (MET) patterns were also observed during the differentiation process. Moreover, whole transcriptome analysis highlighted a response typical of the one observed in liver regeneration and hepatocyte proliferation. While a complete maturation of hepatocytes was yet to be obtained, the results presented in this work provide new insights into the process of liver development and highlight potential targets aimed to improve in-vitro liver regeneration.

Supplementation of arginine, ornithine and citrulline in rainbow trout (Oncorhynchus mykiss): Effects on growth, amino acid levels in plasma and gene expression responses in liver tissue.

Functional amino acids (FAA) regulate metabolic pathways directly linked to health, survival, growth and development. Arginine is a FAA with crucial roles in protein deposition and the immune response. In mammals, supplementation of arginine's precursor amino acid, citrulline, is known to increase circulating arginine to levels beyond direct arginine supplementation, however, citrulline supplementation is poorly studied in fish. To address this knowledge gap, we supplemented the diet of rainbow trout with arginine and its precursor amino acids, ornithine and citrulline, at 3 levels (0.5%, 1% and 2% of the total diet) during a 14-week experiment. We sampled fish at 3 h and 24 h post-feeding to investigate immediate and steady-state effects, respectively. There were no differences in fish growth for any of the diets across a range of indicators. In blood plasma, out of 26 amino acids detected, 11 and 6 displayed significant changes 24 h and 3 h post-prandial, respectively. Arginine, ornithine and citrulline levels were all significantly increased by the citrulline supplemented diets. In muscle, 8 amino acids were significantly altered by supplemented diets, while there were no significant changes in liver. Arginine was increased by 2% citrulline supplementation in muscle tissue. We also investigated the transcriptional responses of urea cycle, nitric oxide cycle and rate-limiting polyamine synthesis enzymes, related to arginine's metabolism, in liver. At both time points, only 2 enzymes were significantly altered by the supplemented diets, however several significant changes were observed comparing 3 h and 24 h post-prandial expression levels. Of these, the paralogous polyamine synthesis enzyme encoding genes ODC1 and ODC2 displayed the largest increases in 3 h post-prandial fish. These findings demonstrate that endogenous synthesis of arginine is possible from a citrulline supplemented diet and improve our understanding of arginine metabolism in fish.

Sodium nitrite negatively affects reproductive ability and offspring survival in female mice.

Sodium nitrite (NaNO2) is an industrial chemical that is frequently used as a food additive to prevent botulism and enhance glossiness, such as curing meat. In addition, in some regions, water source NaNO2 concentrations exceed standard regulatory levels. Whether the excessive intake of NaNO2 has toxic effects on female fertility and fetal development remain unknown. In this study, we administered ICR mice control saline, low-dose NaNO2 (60 mg/kg/day), or high-dose NaNO2 (120 mg/kg/day) by intragastric gavage for 21 days. We then assessed oocyte morphology, spindle-chromosome dynamics, mitochondrial distribution, ATP content, apoptotic cell numbers, DNA damage levels, histone modifications, reactive oxygen species (ROS) levels, and offspring survival. Results showed that NaNO2 treatment decreased oocyte number, impaired polar body extrusion, and increased zona pellucida thickness in oocytes. Furthermore, NaNO2 disrupted MII spindle integrity, caused abnormal mitochondrial distribution, decreased ATP content, and increased levels of ROS and H3K4me2. Moreover, the number of oocytes in early stages of apoptosis and with levels of DNA damage increased in NaNO2-treated mice along with decreased offspring numbers and survival rates. We demonstrated the negative effects of NaNO2 on female reproductive abilities in mice.

The freeze-dried extracts of Rotheca myricoides (Hochst.) Steane & Mabb possess hypoglycemic, hypolipidemic and hypoinsulinemic on type 2 diabetes rat model.

ETHNOPHARMACOLOGICAL RELEVANCE: Rotheca myricoides (Hochst.) Steane & Mabb is a plant species used in traditional medicine for the management of diabetes in the lower eastern part of Kenya (Kitui, Machakos and Makueni Counties, Kenya) that is mainly inhabited by the Kamba community. AIM: This study investigated the antihyperglycaemic, antidyslipidemic and antihyperinsulinemic activity of the freeze-dried extracts of Rotheca myricoides (Hochst.) Steane & Mabb (RME) in an animal model of type 2 diabetes mellitus. METHODS: Type 2 diabetes was induced by dietary manipulation for 56 days via (high fat- high fructose diet) and intraperitoneal administration of streptozocin (30 mg/kg). Forty freshly-weaned Sprague Dawley rats were randomly assigned into the negative control (high fat/high fructose diet), low dose test (50mg/kg RME, high dose test (100mg/kg RME and positive control (Pioglitazone, 20mg/kg) groups. Fasting blood glucose and body weight were measured at weekly intervals. Oral glucose tolerance tests were performed on days 28 and 56. Lipid profile, hepatic triglycerides, fasting serum insulin levels and serum uric acid were determined on day 56. RESULTS: The RME possessed significant antihyperglycemic [FBG: 6.5 ±â€¯0.11 mmol/l (negative control) vs. 4.62 ±â€¯0.13 mmol/l (low dose test) vs. 5.25 ±â€¯0.15 mmol/l in (high dose test) vs. 4.33 ±â€¯0.09 mmol/l (positive control): p < 0.0001] and antihyperinsulinemic effects [1.84 ±â€¯0.19 (negative control) vs. (0.69 ±â€¯0.13 (low dose test) vs. (0.83 ±â€¯0.17 (high dose test) vs. (0.69 ±â€¯0.10 (positive control): F (3, 36) = 0.6421: p < 0.0001. The extracts also possessed significant antidyslipidemic effects [LDL levels: 3.52 ±â€¯0.19 mmol/l (negative control) vs. 0.33 ±â€¯0.14 mmol/l (low dose test) vs. 0.34 ±â€¯0.20 mmol/l (high dose test) vs. 0.33 ±â€¯0.01 mmol/l (positive control): p < 0.0001].RME significantly lowered plasma uric acid levels, as well as hepatic triglycerides and hepatic weights. Network pharmacology analysis indicated that the observed pharmacological effects are mediated via the modulation of Peroxisome proliferator-activated gamma receptor. CONCLUSIONS: The freeze dried extracts of Rotheca myricoides possessed significant antihyperglycemic and antidyslidemic effects. In addition it lowered serum uric levels, as well as hepatic triglycerides and hepatic weight. These results appear to validate the traditional use of this plant species in the management of diabetes mellitus.

Comparative transcriptomic analysis of hypothalamus-pituitary-liver axis in bighead carp (Hypophthalmichthys nobilis) with differential growth rate.

BACKGROUND: Growth rate is one of the most important features for aquaculture species and deciphering its regulation mechanism has great significance both in genetics and in economics. Hypothalamus-pituitary growth axis (HP growth axis) or neuro-endocrine axis plays a vital role in growth regulation in different aquaculture animals. RESULTS: In this study, the HP and liver transcriptomes of two female groups (H and L) with phenotypically extreme growth rate were sequenced using RNA-Seq. A total of 30,524 and 22,341 genes were found expressed in the two tissues, respectively. The average expression levels for the two tissues were almost the same, but the median differed significantly. A differential expression analysis between H and L groups identified 173 and 204 differentially expressed genes (DEGs) in HP and liver tissue, respectively. Pathway analysis revealed that DEGs in HP tissue were enriched in regulation of cell proliferation and angiogenesis while in liver tissue these genes were overrepresented in sterol biosynthesis and transportation. Genomic overlapping analyses found that 4 and 5 DEGs were within growth-related QTL in HP and liver tissue respectively. A deeper analysis of these 9 genes revealed 3 genes were functionally linked to the trait of interest. The expression of 2075 lncRNAs in HP tissue and 1490 in liver tissue were also detected, and some of lncRNAs were highly expressed in the two tissues. CONCLUSIONS: Above all, the results of the present study greatly contributed to the knowledge of the regulation of growth and then assisted the design of new selection strategies for bighead carp with improved growth-related traits.

Schisandra fruits for the management of drug-induced liver injury in China: A review.

BACKGROUND: With increasing use of pharmaceuticals, drug-induced liver injury (DILI) has become a significant therapeutic challenge to physicians all over the world. Drugs based on Schisandra fruits (SF for short, the fruits of Schisandra chinensis or Schisandra sphenanthera) or synthetic analogues of schisandrin C, are commonly prescribed for treating DILI in China. PURPOSE: This review summarizes the literature regarding the application of SF-derived drugs in patients with DILI and current understanding of mechanisms underlying the protective effects of SF against liver injury. METHODS: Keywords related to drug-induced liver injury and Schisandra fruits were searched in the following databases: Pubmed, Cochrane Library, Google Scholar, LiverTox, China National Knowledge Infrastructure (CNKI), Chinese Scientific Journal database (VIP), and Wanfang database. All studies, published in English or Chinese, were included. Clinical study exclusion criteria: if patients received other Chinese herbal medicines in a study, the study will not be included in this review. RESULTS: Clinical studies have shown that SF-derived drugs are effective in inhibiting drug-induced elevation of serum levels of alanine aminotransferase, aspartate transaminase and total bilirubin. Cellular and animal studies have demonstrated that crude SF extracts, lignan compounds found in SF, and SF-derived drugs are effective in protecting the liver against xenobiotic-induced injury. Regulation of cytochrome P450 enzyme activity, anti-oxidation, anti-inflammation and acceleration of liver regeneration are involved in the hepatoprotective mechanisms of SF. CONCLUSION: SF-derived drugs are effective in ameliorating DILI in China. To verify the clinical efficacy of these drugs, high-quality clinical studies are needed.

The effect of micronutrient supplementation on growth and hepatic metabolism in diploid and triploid Atlantic salmon (Salmo salar) parr fed a low marine ingredient diet.

The effects of low marine ingredient diets supplemented with graded levels (L1, L2, L3) of a micronutrient package (NP) on growth and metabolic responses were studied in diploid and triploid salmon parr. Diploids fed L2 showed significantly improved growth and reduced liver, hepatic steatosis, and viscerosomatic indices, while fish fed L3 showed suppressed growth rate 14 weeks post feeding. In contrast, dietary NP level had no effect on triploid performance. Whole body mineral composition, with exception of copper, did not differ between diet or ploidy. Whole fish total AAs and N-metabolites showed no variation by diet or ploidy. Free circulating AAs and white muscle N-metabolites were higher in triploids than diploids, while branch-chained amino acids were higher in diploids than triploids. Diploids had higher whole body α-tocopherol and hepatic vitamins K1 and K2 than triploids. Increased tissue B-vitamins for niacin and whole-body folate with dietary NP supplementation were observed in diploids but not triploids, while whole body riboflavin was higher in diploids than triploids. Hepatic transcriptome profiles showed that diploids fed diet L2 was more similar to that observed in triploids fed diet L3. In particular, sterol biosynthesis pathways were down-regulated, whereas cytochrome P450 metabolism was up-regulated. One­carbon metabolism was also affected by increasing levels of supplementation in both ploidies. Collectively, results suggested that, for optimised growth and liver function, micronutrient levels be supplemented above current National Research Council (2011) recommendations for Atlantic salmon when fed low marine ingredient diets. The study also suggested differences in nutritional requirements between ploidy.

Influence of dietary lipid levels on growth, nutrient utilization, tissue fatty acid composition and desaturase gene expression in silver barb (Puntius gonionotous) fingerlings.

Silver barb (Puntius gonionotus) is considered as a promising medium-sized carp species for freshwater aquaculture in Asia. This study in silver barb was carried out to evaluate the effects of increasing dietary levels of lipid on growth, nutrient utilization, whole-body composition, tissue fatty acid composition and Δ6 fatty acyl desaturase (Δ6 fad) gene expression. Fish (11.3 ±â€¯0.23 g of initial body weight) was fed for 60 days with five experimental diets: FO-0 (control feed); FO-30; FO-60; FO-90 and FO-120 containing 0, 30, 60, 90 and 120 g fish oil kg-1 diet, respectively. Among the diets, the highest specific growth rate (SGR), protein efficiency ratio (PER) and whole-body lipid content, and the lowest feed conversion ratio (FCR) were recorded with FO-120 diet. The saturated fatty acids (SFA) level in the muscle was significantly (P < .05) increased with the enhanced FO supplementation, whereas monounsaturated fatty acids (MUFA) level decreased. Increased level of fish oil in the diet also enhanced the n-3 PUFA and n-3 LC-PUFA (long-chain polyunsaturated fatty acid) in the muscle and liver. The expression of Δ6 fad gene was downregulated, whereas the serum biochemical constituents were either remain unchanged or enhanced with increased FO supplementation in the diets of silver barb.

Long-Term Effects of Dietary Protein and Branched-Chain Amino Acids on Metabolism and Inflammation in Mice.

Aging is the main factor involved in the onset of degenerative diseases. Dietary protein restriction has been shown to increase the lifespan of rodents and improve metabolic phenotype. Branched-chain amino acids (BCAA) can act as nutrient signals that increase the lifespan of mice after prolonged supplementation. It remains unclear whether the combination of protein restriction and BCAA supplementation improves metabolic and immunological profiles during aging. Here, we investigated how dietary protein levels and BCAA supplementation impact metabolism and immune profile during a 12-month intervention in adult male C57BL/6J mice. We found that protein restriction improved insulin tolerance and increased hepatic fibroblast growth factor 21 mRNA, circulating interleukin (IL)-5 concentration, and thermogenic uncoupling protein 1 in subcutaneous white fat. Surprisingly, BCAA supplementation conditionally increased body weight, lean mass, and fat mass, and deteriorated insulin intolerance during protein restriction, but not during protein sufficiency. BCAA also induced pro-inflammatory gene expression in visceral adipose tissue under both normal and low protein conditions. These results suggest that dietary protein levels and BCAA supplementation coordinate a complex regulation of metabolism and tissue inflammation during prolonged feeding.

Zebrafish (Danio rerio): A valuable tool for predicting the metabolism of xenobiotics in humans?

Zebrafish has become a popular model organism in several lines of biological research sharing physiological, morphological and histological similarities with mammals. In fact, many human cytochrome P450 (CYP) enzymes have direct orthologs in zebrafish, suggesting that zebrafish xenobiotic metabolic profiles may be similar to those in mammals. The focus of the review is to analyse the studies that have evaluated the metabolite production in zebrafish over the years, either of the drugs themselves or xenobiotics in general (environmental pollutants, natural products, etc.), bringing a vision of how these works were performed and comparing, where possible, with human metabolism. Early studies that observed metabolic production by zebrafish focused on environmental toxicology, and in recent years the main focus has been on toxicity screening of pharmaceuticals and drug candidates. Nevertheless, there is still a lack of standardization of the model and the knowledge of the extent of similarity with human metabolism. Zebrafish screenings are performed at different life stages, typically being carried out in adult fish through in vivo assays, followed by early larval stages and embryos. Studies comparing metabolism at the different zebrafish life stages are also common. As with any non-human model, the zebrafish presents similarities and differences in relation to the profile of generated metabolites compared to that observed in humans. Although more studies are still needed to assess the degree to which zebrafish metabolism can be compared to human metabolism, the facts presented indicate that the zebrafish is an excellent potential model for assessing xenobiotic metabolism.

Long-Term Dietary Intake of Chia Seed Is Associated with Increased Bone Mineral Content and Improved Hepatic and Intestinal Morphology in Sprague-Dawley Rats.

Chia seeds (Salvia hispanica) provide an unusually high content of α-linolenic acid with several potential health benefits, but few studies have examined the long-term intake of n-3 fatty acid-rich plant foods such as chia. In this work, we investigated some of the effects of a diet containing 10% chia seeds versus a conventional isocaloric diet for 10 and 13 months on body measurements, musculoskeletal system, the liver, and the intestines of 20 male Sprague-Dawley rats assigned into two groups. The n-6/n-3 ratios for the control and chia diets were 7.46 and 1.07, respectively. For the first 10 months of the diet, the body parameters and weights were similar, but at 13 months, the bone mineral content (BMC) of the chia-fed rats was significantly higher than that of the controls whether in total or proximal areas of the left tibia. Also, significant positive correlations were found between the age of the chia group and the bone mineral density, BMC, weight of the musculoskeletal system, final body weight, and skin weight. Liver and intestinal examinations showed improved morphology associated with lower lipid deposit in hepatocytes and increased intestinal muscle layers and crypt size in the chia group. This study provides new data suggesting the potential benefits associated with the long-term intake of chia seeds.

Ammonia-Nitrogen Added to Low-Crude-Protein Diets Deficient in Dispensable Amino Acid-Nitrogen Increases the Net Release of Alanine, Citrulline, and Glutamate Post-Splanchnic Organ Metabolism in Growing Pigs.

Background: Dietary ammonia is rapidly absorbed but poorly used for urea synthesis in pigs fed low-crude-protein (low-CP) diets deficient in dispensable amino acid (DAA)-nitrogen. Objective: We explored the effect of dietary ammonia on net amino acid (AA) balances in portal-drained viscera (PDV) and livers of pigs fed a diet deficient in DAA-nitrogen. Methods: Eight barrows with an initial body weight (BW) of 26.5 ± 1.4 kg (mean + SD) were surgically fitted with 4 catheters each (portal, hepatic, and mesenteric veins and carotid artery). The pigs were restricted-fed (2.8 × 191 kcal/kg BW0.60) for 7 d, and every 8 h a diet deficient in DAA-nitrogen supplemented with increasing amounts of ammonia-nitrogen (CP = 7.76%, 9.27%, and 10.77% for the control and low- and high-ammonia diets, respectively). The treatment sequence was based on a 3 × 3 Latin-square design with 3 consecutive periods. On the last day of each period, blood flows in portal and hepatic veins were determined with a continuous infusion of ρ-amino hippuric acid into the mesenteric vein. Consecutive blood samples were taken for AA concentration in blood plasma, and AA balances were calculated for PDV and the liver. Results: Cumulative release of citrulline (Cit) and proline (Pro) increased with ammonia supplementation in PDV but decreased for glutamine (Gln) and glycine (Gly) (Gln: -19.32 ± 3.56, -32.50 ± 3.73, and -42.11 ± 3.55 mmol/meal for the control and low- and high-ammonia groups, respectively; P ≤ 0.05). Cumulative release of alanine (Ala), glutamic acid (Glu), and Gln increased with ammonia supplementation across the liver (P ≤ 0.05). When combined, PDV+liver, the cumulative release of Ala, Cit, and Glu increased with ammonia-nitrogen supplementation (P ≤ 0.05). Conclusion: Dietary ammonia could be used as a nitrogen supplement to increase the synthesis of Ala, Cit, and Glu across splanchnic organs in pigs fed a diet deficient in DAA-nitrogen.