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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]

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.