Fructose induces hepatic steatosis in adolescent mice linked to the disorders of lipid metabolism, bile acid metabolism, and autophagy.

The effects of excessive fructose intake on the development and progression of metabolic disorders have received widespread attention. However, the deleterious effects of fructose on the development of hepatic metabolic disease in adolescents and its potential mechanisms are not fully understood. In this study, we investigated the effects of isocaloric fructose-rich diets on the liver of adolescent mice. The results showed that fructose-rich diets had no effect on the development of obesity in the adolescent mice, but did induce hepatic lipid accumulation. Besides, we found that fructose-rich diets promoted hepatic inflammatory responses and oxidative stress in adolescent mice, which may be associated with activation of the NLRP3 inflammasome and inhibition of the Nrf2 pathway. Furthermore, our results showed that fructose-rich diets caused disturbances in hepatic lipid metabolism and bile acid metabolism, as well as endoplasmic reticulum stress and autophagy dysfunction. Finally, we found that the intestinal barrier function was impaired in the mice fed fructose-rich diets. In conclusion, our study demonstrates that dietary high fructose induces hepatic metabolic disorders in adolescent mice. These findings provide a theoretical foundation for fully understanding the effects of high fructose intake on the development of hepatic metabolic diseases during adolescence.

Zearalenone induces apoptosis and autophagy by regulating endoplasmic reticulum stress signalling in porcine trophectoderm cells.

Zearalenone (ZEA), a mycotoxin produced mainly by fungi belonging to Fusarium species in foods and feeds, causes a serious hazard to humans and animals. Numerous studies have revealed that ingesting ZEA can disrupt the reproductive function and impair the reproductive process in animals. This experiment was to investigate the toxicological effect and the mechanism of ZEA exposure on reproduction in pigs during early stages of pregnancy. In the present study, we treated with 0 to 80 µmol/L ZEA for 12 or 24 h in trophoblast ectoderm (pTr) cells. The results showed that ZEA had significantly decreased cell proliferation (P < 0.05), which was accompanied by DNA damage-related cell cycle arrest at G2/M phase, activation of the apoptosis and endoplasmic reticulum (ER) stress, as well as impairment of barrier function (P < 0.05). Western blot analysis and transmission electron microscopy (TEM) showed that exposure to ZEA can activation of autophagy in pTr cells. Importantly, pretreatment with chloroquine (CQ) or 3-methyladenine (3-MA) led to increased apoptosis in pTr cells. Interestingly, pTr cells pretreated with 4-phenylbutyric acid (4-PBA), an inhibitor of ER stress, resulted in reduced cell death in pTr cells, indicating a critical role for ER stress in the activation of autophagy. In conclusion, these results reveal that ZEA-triggered ER stress is critical for the cell fate decision of pTr cells during early porcine embryonic development. Application of small molecules with ability of blocking ER stress might be therapeutic option to reduce the deleterious effect of ZEA in pregnant animals.

Protective effect of glucosamine on zearalenone-induced reproductive toxicity and placental dysfunction in mice.

This study was conducted to determine the effects of glucosamine (GlcN) on zearalenone (ZEA)-induced reproductive toxicity and placental dysfunction in mice. The pregnant mice were randomly divided into one of the four groups, such as the control group, the ZEA group, the GlcN group, and the GlcN plus ZEA group. Reproductive toxicity was induced by consecutive gavages of ZEA at 5 mg/kg body weight during gestational days (GDs 0-14) and in the presence or absence of oral administration of GlcN (0.5 mM). The results showed that GlcN significantly alleviated the decrease of growth performance induced by ZEA exposure of pregnant mice. Meanwhile, ZEA ingestion significantly reduced the number and weight of fetuses, and reduction of placenta weight. Moreover, results of blood biochemical markers indicated that ZEA exposure led to increased oxidative stress levels in pregnant mice. Further analyses demonstrated that ZEA inhibited placental development, resulted in placental inflammation, increased the expression of pro-apoptotic proteins, and decreased the expression of placental tight junction proteins, which were reversed by the administration of GlcN. Results of western blot revealed that GlcN reversed ZEA-mediated phenotype by activating PI3K, while inhibiting MAPK signaling pathway. All these findings showed that GlcN was effective in the protection against ZEA-induced placental dysfunction and reproductive toxicity in pregnant mice. Supplementation of GlcN might be potential nutritional intervention with an ability to alleviate ZEA-induced toxicity in pregnant mice.

Resveratrol alleviates enterotoxigenic Escherichia coli K88-induced damage by regulating SIRT-1 signaling in intestinal porcine epithelial cells.

This study found that resveratrol pretreatment attenuated porcine intestinal epithelial cell damage caused by enterotoxigenic Escherichia coli (ETEC) K88 in vitro and the protective effects of resveratrol were associated with SIRT-1 signaling. ETEC K88 is a main intestinal pathogen for post-weaning diarrhea (PWD) in piglets. With the strict ban on antibiotics in animal feed, people are seeking effective antibiotic substitutes to protect the intestinal system against harmful pathogenic bacteria. This study was conducted to evaluate the effects of resveratrol, a natural plant polyphenol, on ETEC K88-induced cellular damage in porcine enterocytes and underlying mechanisms. Intestinal porcine epithelial cell line 1 (IPEC-1) cells, pretreated with or without resveratrol (30 µM, 4 h), were challenged with ETEC K88 (MOI = 1 : 10) for 3 h. The results showed that ETEC K88 infection induced severe damage and dysfunction in IPEC-1 cells, as evidenced by a reduced cell viability, decreased tight junctions, mitochondrial dysfunction, and autophagy. It is noteworthy that IPEC-1 cells pre-treated with resveratrol improved their capacity for resistance to most of these abnormal phenotypes caused by ETEC K88 infection. Furthermore, we found that the activation of SIRT-1 signaling was associated with the benefits of resveratrol, as demonstrated by EX-527, an inhibitor of SIRT-1, which reversed most of the protective effects of resveratrol. In conclusion, these results indicated that resveratrol could protect intestinal epithelial cells against ETEC K88 infection by activating SIRT-1 signaling. These findings provide new insights into the role of resveratrol in maintaining intestinal physiological functions.

Glucosamine alleviates zearalenone-induced damage to porcine trophectoderm cells by activating the PI3K/AKT signaling pathway.

As one of the mycotoxins commonly found in feed and food, zearalenone (ZEA) mainly harms the reproductive functions of humans and animals. In our study, we investigated the protective effects of glucosamine (GlcN) on ZEA-induced apoptosis and oxidative damage of porcine trophectoderm (pTr) cells. Our results showed that 0.5 mmol L-1 GlcN significantly alleviated ZEA-induced decline in pTr cell viability. In addition, GlcN also significantly reversed other toxicity of ZEA to pTr cells, including G2/M phase arrest, DNA damage, reactive oxygen species (ROS) production, and barrier function disruption. Further studies indicated that GlcN can reduce apoptosis and autophagy in pTr cells in response to ZEA treatment. These results were confirmed by flow cytometry, transmission electron microscopy (TEM) and western blotting to detect the expressions of apoptosis and autophagy related proteins. Notably, GlcN activated the expressions of the PI3K/AKT signaling pathway related proteins, suggesting that its protective effect on pTr cells may be mediated by the PI3K/AKT signaling pathway. To demonstrate this mechanism, we used the PI3K/AKT pathway inhibitor wortmannin to pretreat pTr cells, and showed that the protective effect of GlcN on ZEA-induced pTr cytotoxicity was eliminated. In conclusion, GlcN was able to alleviate ZEA-induced toxic effects in pTr cells. This study also provides a theoretical basis for GlcN alleviating the adverse effects of ZEA on early embryo development and proved its potential application prospects.

Kaempferol attenuates diquat-induced oxidative damage and apoptosis in intestinal porcine epithelial cells.

Kaempferol, a flavonol component of plants, is well-known to exhibit multiple bioactivities, such as anti-oxidative and anti-apoptotic effects. However, the underlying mechanisms responsible for the beneficial effects remain elusive. This study was conducted to test the hypothesis that kaempferol attenuated diquat-induced oxidative damage and intestinal barrier dysfunction by ameliorating oxidative damage and apoptosis in intestinal porcine epithelial cells. Compared with the control group, diquat treatment led to enhanced intracellular ROS production, increased mitochondrial depolarization, and apoptosis, which were accompanied by cell cycle arrest at the G1 phase, reduced cell migration, and disrupted intestinal epithelial barrier function. These effects triggered by diquat were reversed by kaempferol. Further study showed that the protective effect of kaempferol was associated with an enhanced mRNA level of genes related to cell cycle progression (cyclin D1, CDK4, and E2F1) and genes implicated in the anti-oxidant system (GSR, GSTA4, and HO-1), up-regulated abundance of tight junctions (ZO-1, ZO-2, occludin, and claudin-4), as well as enhanced Nrf2, an anti-oxidant transcription factor. In conclusion, we revealed a functional role of kaempferol in the intestinal barrier. Ingestion of kaempferol-rich foods might be a potential strategy to improve the integrity and function of enterocytes.

Cellular microRNA, miR-1343-5p, modulates IFN-I responses to facilitate feline panleukopenia virus replication by directly targeting IRAK1 gene.

Feline panleukopenia is an acute, highly contagious, and fatal infectious disease caused by feline panleukopenia virus (FPV) and has led to severe consequences on pets, economically important animals, and the wildlife industry. MicroRNAs (miRNAs) play significant roles in the host-pathogen interaction by modulating cellular factors expression which are essential for viral replication or host innate immune response to infection. However, the role of host miRNA response in FPV infection remains to be discovered. In this study, we screened nine host miRNAs associated with FPV infection that were previously implicated in innate immunity or antiviral functions. We found that miR-1343-5p overexpression strongly promoted FPV-BJ04 genomic DNA. Subsequently, the expression of host miR-1343-5p was upregulated by FPV-BJ04 infection in vitro and in vivo. In addition, we demonstrated that miR-1343-5p was a negative regulator of the IFN-I signaling pathway, thereby promoting FPV infection. Bioinformatic analysis combined with molecular biological assay indicated that interleukin-1 receptor-associated kinase 1 (IRAK1) is a putative target of miR-1343-5p. Collectively, our findings emphasize the importance of miR-1343-5p in host defense against FPV, thus, enhancing our understanding of its pathogenic mechanism.

Analysis of the microRNA expression profiles in feline kidney cell line infected with feline panleukopenia virus.

MicroRNAs (miRNAs) play crucial roles in post-transcriptional regulation of gene expression in many biological processes. Feline panleukopenia virus (FPV) is a highly infectious pathogen that can cause severe disease in pets, economically important animals and wildlife. In this study, miRNAs associated with FPV infection were identified using high-throughput sequencing. Our results showed that 673 known miRNAs and 278 novel miRNAs were identified and 57 significantly differential expression miRNAs were found post-FPV infection in feline kidney cell line. Stem-loop qRT-PCR was applied to validate the expression of the randomly selected miRNAs; the results were consistent with the sequencing data. Furthermore, the target genes of differential expression miRNAs were analyzed and predicated by GO and KEGG pathway. Altogether, our analysis provides a potential link between miRNA expression and the pathogenesis of FPV infection.