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The origin of duodenal purine bases (PB) was studied in a digestion experiment with four heifers, cannulated in the rumen and duodenum, which received a basal concentrate (152 g crude protein (CP) per kg dry matter (DM)) together with barley straw (85 :15 fresh weight basis) or the same concentrate supplemented with soya-bean meal, carbohydrate-treated soya-bean meal, maize gluten meal or fish meal to increase its protein content to 192 g/kg DM. Treatments were assigned to the four animals in five experimental periods according to an incomplete Latin-square design. Each 30-day period included 20 days of change-over adaptation and 10 days of experimental measurements. The flow of digests entering the duodenum was estimated using Yb and acid-detergent insoluble ash as indigestible markers according to a double-marker system and microbial nitrogen (N) and PB were labelled with 15N infused into the rumen. The proportion of duodenal PB of microbial origin estimated from 15N enrichment of PB-N averaged 0.66 (s.e. 0.029) and did not differ between treatments nor when protozoa or bacteria associated with liquid (LAB) and solid (SAB) fractions were used as a reference sample. On average microbial contribution to duodenal non-ammonia N was higher when estimated from the PB/N ratio than from 15N (0.67 v. 0.55 (s.e. 0.015)) although differences were small and not significant when LAB was the reference sample (0.58 v. 0.52 (s.e. 0.018)) reflecting the higher PB/N ratio of this fraction compared with SAB and protozoa (2.04 v.1.65 and 1.60 (s.e. 0.04) mmol/g). Considering only the duodenal PB of microbial origin resulted in estimates of microbial N synthesis from the PB/N ratio of SAB similar to those derived from 15N enrichment of both bacterial fractions (12.9 v. 13.5 and 13.3 (s.e.0.83)g/kg of organic matter apparently digested in the rumen OMADR)) but underestimated the values derived from LAB (9.9 g/kg OMADR). Regardless of the estimation... [ABSTRACT FROM AUTHOR]

The effect of post-ruminal fermentation on faecal output of purine bases (PB) and urinary excretion of their derivatives (PD) was studied by the infusion of yeast RNA (2·9 g/day), corn starch (100 g/day), cellulose (200 g/day) and saline solutions into the gastro-intestinal tract offour sheep (35·4 kg live weight) fitted with caecal and duodenal catheters and given 0-80 kg/day alfalfa hay. All substrates were infused into the caecum except cellulose that was infused into the proximal duodenum.The infusion of RNA did not affect either the faecal excretion of PB or the urinary excretion of allantoin or total PD, although xanthine excretion increased significantly from <0·01 to 0·12 mmol/day.Starch and cellulose infusions promoted a significant increase in the faecal excretion of diaminopimelic acid (206 and 159 v. 131 mg/day) and PB (4·55 and 3·62 v. 2·29 mmol/day) and modified the partitioning of total nitrogen losses between faeces and urine. The urinary excretion of allantoin and total PD were not affected by the caecal infusion of starch (6·60 and 22·9 v. 7·02 and 22·8 mmol/day) but both tended to increase with the duodenal infusion of cellulose (7·75 and 26·4 mmol/day).It is concluded that the urinary excretion ofPD is independent of either the supply of nucleic acids to the caecum or the extent of hind gut fermentation although it may be affected by variations in the flow of undigested fibre along the small intestine. [ABSTRACT FROM PUBLISHER]

Four adult ewes (mean weight 42·6 kg) fitted with oesophageal fistulae were given 5 mmol/day ofallantoin or saline solutions by intrajugular continuous infusion. The experiment was a randomized cross-over design, with two consecutive 3-day infusion periods. One kg/day fresh matter of either chopped or pelleted fescue hay was distributed over 12 meals and salivary flow estimated from dilution of Co-EDTA infused into the buccal cavity. Allantoin infusion resulted in a rapid increase in its plasma concentration (84 to 128 (s.e. 1·5) μmol/l) and urinary excretion (9·6 to 13·3 (s.e. 0·18) mmol/day) without significant differences between diets. Salivary allantoin also increased (4·6 to 6·4 (s.e. 0·60) ymol/1) in response to infusion, although the concentration of total purine derivatives in saliva was only proportionately 0·08 that of plasma. Renal and salivary clearance of oxypurines, allantoin (78 (s.e. 5·0) ml/min and 13 (s.e. 0·7) ml/h), uric acid (466 (s.e. 98·0) ml/min and 45 (s.e. 9·8) ml/h) and creatinine (104 (s.e. 3·0) ml/min and 14 (s.e. 1·1) ml/h) were constant, irrespective of diet and infusion treatments. Urinary recovery of infused allantoin averaged 0·78 (s.e. 0·031) but salivary secretion, equivalent to about 0·003 of urinary losses, was not the explanation for the incomplete recovery. [ABSTRACT FROM PUBLISHER]

Abstract: Background: Electrical bioimpedance (BI) has been used to indirectly measure steatosis. This method has not yet been established in the clinics thus experimental studies are needed in big animals. We assessed BI to measure liver steatosis in porcine animals. Methods: Twelve large-white × Landrace pigs weighing 35 kg were allocated to a study (n = 9) and a control group (n = 3). A special diet was used to promote steatosis among the study group: methionine deficient and choline-restricted diet that contains supplements of cholesterol, collate and excess of saturated fat. Control group animals were fed a normal diet. A new tetrapolar electrode model was used for BI measurement, which were performed during open laparotomy by inserting a probe into one of the lobes. Measurements were done in the third and fourth segments of the pig liver, placing the probe either on the surface or inserted into the parenchyma of the liver. Open biopsies were obtained at the end of the measurements. Histological samples were processed and stained with hematoxylin-eosin to estimate macrosteatosis. Pearson correlation coefficient between BI and percentage steatosis were calculated at different frequencies. Results: After 4 months of the special diet all the animals in the study group developed steatosis (90% to 20%), whereas none of the control group was affected. Pearson correlation coefficients between BI and percentage of steatosis were significant (0.877–0.878) with the best correlations obtained with a probe placed on the fourth segment of the liver surface and the best frequency to perform the measurements being 50 and 75 kHz. Conclusions: BI is an accurate, fast method for steatosis measurements, that is easier and cheaper than either open or needle biopsy. [Copyright &y& Elsevier]

Introduction: The lower rates of cardiovascular disease in Southern Europe could be partially explained by the low prevalence of lipid-rich atheroma plaques. Consumption of certain foods affects the progression and severity of atherosclerosis. We investigated whether the isocaloric inclusion of walnuts within an atherogenic diet prevents phenotypes predicting unstable atheroma plaque in a mouse model of accelerated atherosclerosis., Methods: Apolipoprotein E-deficient male mice (10-week-old) were randomized to receive a control diet (9.6% of energy as fat, n = 14), a palm oil-based high-fat diet (43% of energy as fat, n = 15), or an isocaloric diet in which part of palm oil was replaced by walnuts in a dose equivalent to 30 g/day in humans ( n = 14). All diets contained 0.2% cholesterol., Results: After 15 weeks of intervention, there were no differences in size and extension in aortic atherosclerosis among groups. Compared to control diet, palm oil-diet induced features predicting unstable atheroma plaque (higher lipid content, necrosis, and calcification), and more advanced lesions (Stary score). Walnut inclusion attenuated these features. Palm oil-based diet also boosted inflammatory aortic storm (increased expression of chemokines, cytokines, inflammasome components, and M1 macrophage phenotype markers) and promoted defective efferocytosis. Such response was not observed in the walnut group. The walnut group's differential activation of nuclear factor kappa B (NF-κB; downregulated) and Nrf2 (upregulated) in the atherosclerotic lesion could explain these findings., Conclusion: The isocaloric inclusion of walnuts in an unhealthy high-fat diet promotes traits predicting stable advanced atheroma plaque in mid-life mice. This contributes novel evidence for the benefits of walnuts, even in an unhealthy dietary environment., Competing Interests: Research supported by the California Walnut Commission (CWC, Folsom, CA), which had no involvement in the study design, data collection, analyses, interpretation of the data or writing of the manuscript. AS-V has received research funding through his institution and support to attend professional meetings from the California Walnut Commission (CWC, Folsom, CA). The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Lázaro, Bobi, Cofán, Kapravelou, Amor, Surra, Gómez-Guerrero, Ortega, Osada, Dantas and Sala-Vila.)

Thioredoxin domain containing 5 (TXNDC5) is a protein disulfide isomerase involved in several diseases related to oxidative stress, energy metabolism and cellular inflammation. In a previous manuscript, a negative association between fatty liver development and hepatic Txndc5 expression was observed. To study the role of TXNDC5 in the liver, we generated Txndc5 -deficient mice. The absence of the protein caused an increased metabolic need to gain weight along with a bigger and fatter liver. RNAseq was performed to elucidate the putative mechanisms, showing a substantial liver overexpression of serum amyloid genes ( Saa1 , Saa2 ) with no changes in hepatic protein, but discrete plasma augmentation by the gene inactivation. Higher levels of malonyldialdehyde, apolipoprotein A1 and platelet activating factor-aryl esterase activity were also found in serum from Txndc5 -deficient mice. However, no difference in the distribution of high-density lipoproteins (HDL)-mayor components and SAA was found between groups, and even the reactive oxygen species decreased in HDL coming from Txndc5 -deficient mice. These results confirm the relation of this gene with hepatic steatosis and with a fasting metabolic derive remedying an acute phase response. Likewise, they pose a new role in modulating the nature of HDL particles, and SAA-containing HDL particles are not particularly oxidized.

Erythrodiol is a terpenic compound found in a large number of plants. To test the hypotheses that its long-term administration may influence hepatic transcriptome and this could be influenced by the presence of APOA1-containing high-density lipoproteins (HDL), Western diets containing 0.01% of erythrodiol (10 mg/kg dose) were provided to Apoe - and Apoa1 -deficient mice. Hepatic RNA-sequencing was carried out in male Apoe -deficient mice fed purified Western diets differing in the erythrodiol content. The administration of this compound significantly up- regulated 68 and down-regulated 124 genes at the level of 2-fold change. These genes belonged to detoxification processes, protein metabolism and nucleic acid related metabolites. Gene expression changes of 21 selected transcripts were verified by RT-qPCR. Ccl19-ps2 , Cyp2b10 , Rbm14-rbm4 , Sec61g , Tmem81 , Prtn3 , Amy2a5 , Cyp2b9 and Mup1 showed significant changes by erythrodiol administration. When Cyp2b10 , Dmbt1 , Cyp2b13 , Prtn3 and Cyp2b9 were analyzed in female Apoe -deficient mice, no change was observed. Likewise, no significant variation was observed in Apoa1 - or in Apoe- deficient mice receiving doses ranging from 0.5 to 5 mg/kg erythrodiol. Our results give evidence that erythrodiol exerts a hepatic transcriptional role, but this is selective in terms of sex and requires a threshold dose. Furthermore, it requires an APOA1-containing HDL.

The calcium-activated potassium channel KCa3.1 controls different cellular processes such as proliferation and volume homeostasis. We investigated the role of KCa3.1 in experimental and human liver fibrosis. KCa3.1 gene expression was investigated in healthy and injured human and rodent liver. Effect of genetic depletion and pharmacological inhibition of KCa3.1 was evaluated in mice during carbon tetrachloride induced hepatic fibrogenesis. Transcription, protein expression and localisation of KCa3.1 was analysed by reverse transcription polymerase chain reaction, Western blot and immunohistochemistry. Hemodynamic effects of KCa3.1 inhibition were investigated in bile duct-ligated and carbon tetrachloride intoxicated rats. In vitro experiments were performed in rat hepatic stellate cells and hepatocytes. KCa3.1 expression was increased in rodent and human liver fibrosis and was predominantly observed in the hepatocytes. Inhibition of KCa3.1 aggravated liver fibrosis during carbon tetrachloride challenge but did not change hemodynamic parameters in portal hypertensive rats. In vitro, KCa3.1 inhibition leads to increased hepatocyte apoptosis and DNA damage, whereas proliferation of hepatic stellate cells was stimulated by KCa3.1 inhibition. Our data identifies KCa3.1 channels as important modulators in hepatocellular homeostasis. In contrast to previous studies in vitro and other tissues this channel appears to be anti-fibrotic and protective during liver injury.

Background and Aims: The present study was designed to verify the influence of acute fat loading on high density lipoprotein (HDL) composition, and the involvement of liver and different segments of small intestine in the changes observed., Methods and Results: To address these issues, rats were administered a bolus of 5-ml of extra-virgin olive oil and sacrificed 4 and 8 hours after feeding. In these animals, lipoproteins were analyzed and gene expressions of apolipoprotein and HDL enzymes were assessed in duodenum, jejunum, ileum and liver. Using this experimental design, total plasma and HDL phospholipids increased at the 8-hour-time-point due to increased sphingomyelin content. An increase in apolipoprotein A4 was also observed mainly in lipid-poor HDL. Increased expression of intestinal Apoa1, Apoa4 and Sgms1 mRNA was accompanied by hepatic decreases in the first two genes in liver. Hepatic expression of Abcg1, Apoa1bp, Apoa2, Apoe, Ptlp, Pon1 and Scarb1 decreased significantly following fat gavage, while no changes were observed for Abca1, Lcat or Pla2g7. Significant associations were also noted for hepatic expression of apolipoproteins and Pon1. Manipulation of postprandial triglycerides using an inhibitor of microsomal transfer protein -CP-346086- or of lipoprotein lipase -tyloxapol- did not influence hepatic expression of Apoa1 or Apoa4 mRNA., Conclusion: All these data indicate that dietary fat modifies the phospholipid composition of rat HDL, suggesting a mechanism of down-regulation of hepatic HDL when intestine is the main source of those particles and a coordinated regulation of hepatic components of these lipoproteins at the mRNA level, independently of plasma postprandial triglycerides.