Search

The aim of this study was to assess the effect of nucleotides administration on growth performance and immune response in post-weaning piglets. Twenty-eight male weaned piglets, homogeneous for age and weight were randomly allocated to two experimental treatments. Treated group (T) was daily orally administered 0.8 g/head of a mixture of nucleotides suspended in 2.1 mL water solution; while control group (C) received 2.1 mL saline solution. Body weight (BW) and average daily gain (ADG) were individually recorded weekly, while feed intake (FI), and gain:feed (G:F) were recorded and calculated on pen basis. Faecal score was evaluated every seven days. On day 0, 9, 18 and 27 blood samples were collected to determine IgA, IgG and haptoglobin concentration. At day 28 all piglets were sacrificed, and tissue samples of ileal Peyer’s patches were collected for the evaluation of IL1α, IL1β, IL6, IL10, TNFα, TLR2, TLR4 and PPARγ gene expression. Nucleotides supplementation significantly increased BW (17.37 vs. 19.00 kg/pig; p = <.01), ADG (.351 vs.400 kg/d; p <.01), and FI (3.96 vs. 4.39 kg/d; p <.01), but not G:F (.61 vs.64; p =.29). Faecal consistency was not different between the experimental groups and no occurrence of diarrhoea was reported. IgA and IgG content in blood was not influenced by the treatment, as well as gene expression of inflammatory cytokines in Peyer’s patches. The present trial shows that nucleotide administration is able to improve growth performance of post-weaning piglets, with no effects on inflammatory response and the expression of immune-related genes. Highlights Nucleotides administration increased BW, ADG and FI. Nucleotides did not affect inflammatory and immune response.

A new series of derivatives of the PPAR alpha/gamma dual agonist 1 allowed us to identify the ligand (S)-6 as a potent partial agonist of both PPAR alpha and gamma subtypes. X-ray studies in PPAR gamma revealed two different binding modes of (S)-6 to the canonical site. However, (S)-6 was also able to bind an alternative site as demonstrated by transactivation assay in the presence of a canonical PPAR gamma antagonist and supported from docking experiments. This compound did not activate the PPAR gamma-dependent program of adipocyte differentiation inducing a very less severe lipid accumulation compared to rosiglitazone but increased the insulin-stimulated glucose uptake in 3T3-L1 adipocytes. Finally, (S)-6 inhibited the Cdk5-mediated phosphorylation of PPAR gamma at serine 273 that is currently considered the mechanism by which some PPAR gamma partial agonists exert antidiabetic effects similar to thiazolidinediones, without showing their typical side effects. This is the first PPAR alpha/gamma dual agonist reported to show this inhibitory effect representing the potential lead of a new class of drugs for treatment of dyslipidemic type 2 diabetes., QC 20200416

Objectives:The simultaneous presence of cardiac and renal diseases is a pathological condition that leads to increased morbidity and mortality. Several lines of evidence have suggested that lipid dysmetabolism and mitochondrial dysfunction are pathways involved in the pathological processes affecting the heart and kidney. In the salt-loaded spontaneously hypertensive stroke-prone rat (SHRSP), a model of cardiac hypertrophy and nephropathy that shows mitochondrial alterations in the myocardium, we evaluated the cardiorenal effects of fenofibrate, a peroxisome proliferator-activated receptor alpha (PPAR) agonist that acts by modulating mitochondrial and peroxisomal fatty acid oxidation.Methods:Male SHRSPs aged 6-7 weeks were divided in three groups: standard diet (n=6), Japanese diet with vehicle (n=6), and Japanese diet with fenofibrate 150mg/kg/day (n=6) for 5 weeks. Cardiac and renal functions were assessed in vivo by MRI, ultrasonography, and biochemical assays. Mitochondria were investigated by transmission electron microscopy, succinate dehydrogenase (SDH) activity, and gene expression analysis.Results:Fenofibrate attenuated cardiac hypertrophy, as evidenced by histological and MRI analyses, and protected the kidneys, preventing morphological alterations, changes in arterial blood flow velocity, and increases in 24-h proteinuria. Cardiorenal inflammation, oxidative stress, and cellular senescence were also inhibited by fenofibrate. In salt-loaded SHRSPs, we observed severe morphological mitochondrial alterations, reduced SDH activity, and down-regulation of genes regulating mitochondrial fatty-acid oxidation (i.e. PPAR, SIRT3, and Acadm). These changes were counteracted by fenofibrate. In vitro, a direct protective effect of fenofibrate on mitochondrial membrane potential was observed in albumin-stimulated NRK-52E renal tubular epithelial cells.Conclusion:The results suggest that the cardiorenal protective effects of fenofibrate in young male salt-loaded SHRSPs, QC 20180518