Effects of Dietary l-Glutamine Supplementation on the Intestinal Function and Muscle Growth of Piglets.

The aim of this study was to investigate the effects of dietary l-glutamine (Gln) supplementation on the morphology and function of the intestine and the growth of muscle in piglets. In this study, sixteen 21-day-old piglets were randomly divided into two groups: the Control group (fed a basal diet) and the Gln group (fed a basal diet supplemented with 0.81% Gln). Blood, gut, and muscle samples were collected from all piglets on Day 20 of the trial. Compared with the Control group, the supplementation of Gln increased (p < 0.05) the villus height, villus width, villus surface area, and villus height/crypt depth ratio of the small intestine. Furthermore, the supplementation of Gln increased (p < 0.05) total protein, total protein/DNA, and RNA/DNA in both the jejunum and ileum. It also increased (p < 0.05) the concentrations of carnosine and citrulline in the jejunal mucosa, as well as citrulline and cysteine concentrations in the ileum. Conversely, Gln supplementation decreased (p < 0.05) Gln concentrations in both the jejunum and ileum, along with ß-aminoisobutyric acid and 1-Methylhistidine concentrations, specifically in the ileum. Subsequent research revealed that Gln supplementation increased (p < 0.05) the mRNA levels for glutathione-S-transferase omega 2 and interferon-ß in the duodenum. In addition, Gln supplementation led to an increase (p < 0.05) in the number of Lactobacillus genus in the colon, but a decrease (p < 0.05) in the level of HSP70 in the jejunum and the activity of diamine oxidase in plasma. Also, Gln supplementation reduced (p < 0.05) the mRNA levels of glutathione-S-transferase omega 2 and interferon stimulated genes, such as MX1, OAS1, IFIT1, IFIT2, IFIT3, and IFIT5 in both the jejunum and ileum, and the numbers of Clostridium coccoides, Enterococcus genus, and Enterobacterium family in the colon. Moreover, Gln supplementation enhanced (p < 0.05) the concentrations of total protein, RNA/DNA, and total protein/DNA ratio in the longissimus dorsi muscle, the concentrations of citrulline, ornithine, arginine, and hydroxyproline, and the mRNA level of peptide transporter 1, while reducing the contents of hydrogen peroxide and malondialdehyde and the mRNA level of glutathione-S-transferase omega 2 in the longissimus dorsi muscle. In conclusion, dietary Gln supplementation can improve the intestinal function of piglets and promote the growth of the longissimus dorsi muscle.

Retinoic acid enhances ovarian steroidogenesis by regulating granulosa cell proliferation and MESP2/STAR/CYP11A1 pathway.

INTRODUCTION: Ovarian steroidogenesis not only affects the embryonic development and pregnancy outcome, but also associates with many diseases in mammals and women. Exploring the nutrients and mechanisms influencing ovarian steroidogenesis is critical to maintaining the optimal reproductive performance, as well as guaranteeing body health. OBJECTIVES: This research aimed to explore the effect of retinol metabolism on ovarian steroidogenesis and the underlying mechanisms. METHODS: Comparative transcriptomic analysis of ovaries from normal and low reproductive performance sows were performed to identify the main causes leading to low fertility. The metabolites regulating steroid hormones synthesis were investigated in ovarian granulosa cells. Gene interference, overexpression, dual-luciferase reporter assays, chromatin immunoprecipitation and transcriptome analysis were further conducted to explore the underlying mechanisms of Aldh1a1 mediating ovarian steroidogenesis. RESULTS: Transcriptome analysis of ovaries from normal and low reproductive performance sows showed the significant differences in both retinol metabolism and steroid hormones synthesis, indicating retinol metabolism probably influenced steroid hormones synthesis. The related metabolite retinoic acid was furtherly proven a highly active and potent substance strengthening estrogen and progesterone synthesis in ovarian granulosa cells. For the first time, we revealed that retinoic acid synthesis in porcine and human ovarian granulosa cells was dominated by Aldh1a1, and required the assistance of Aldh1a2. Importantly, we demonstrated that Aldh1a1 enhanced the proliferation of ovarian granulosa cells by activating PI3K-Akt-hedgehog signaling pathways. In addition, Aldh1a1 regulated the expression of transcription factor MESP2, which targeted the transcription of Star and Cyp11a1 through binding to corresponding promoter regions. CONCLUSION: Our data identified Aldh1a1 modulates ovarian steroidogenesis through enhancing granulosa cell proliferation and MESP2/STAR/CYP11A1 pathway. These findings provide valuable clues for improving ovarian health in mammals.

Establishment and application of high throughput screening cell model for nutrient regulation of embryonic development.

Embryo development exerts far-reaching influence on pregnancy outcome, postnatal development and lifelong health. Thereafter, to select functional nutrients to improve embryo development is of great importance. Herein, a stable porcine trophectoderm cell line expressing a luciferase reporter gene driven by a 1,009 bp PCNA gene promoter was constructed through lentiviral transduction and G418 selection. A high throughput screening assay was subsequently developed using the stable reporter cell line to screen a library of 225 nutrients. Seven nutrients with a minimum Z-score of 2.0 were initially identified to be capable of enhancing embryonic development. Among these nutrients, resveratrol, apigenin, and retinol palmitate were furtherly confirmed the beneficial effects for embryo development. Resveratrol significantly increased the expression of key genes involved in pTr cell proliferation and the number of S-phase cells. Resveratrol was furtherly confirmed to promote the expression of key genes in trophoblast development and increase embryo adhesion rate in vitro. Similarly, dietary 0.05% resveratrol supplementation significantly increased the number of embryo attachment and serum level of P4 and E2 in rats. Resveratrol could also improve maternal antioxidant levels and reduce intracellular ROS. Collectively, a high throughput screening cell model for nutrient regulation of embryonic development was established, which can be used to highly effectively select the potential candidates for embryo development. These findings have great implications for exploring optimal functional nutrients to improve embryo development, ultimately beneficial for pregnancy outcome, offspring postnatal development and lifelong health for human beings and mammalian animals.

Methionine influences the profile of intestinal antibiotic resistome through inhibiting the growth of Escherichia coli.

Antibiotic resistance genes (ARGs) are a new type of environmental pollutant. However, studies have mainly focused on the distribution characteristics of ARGs in the livestock environment, lacking of studies on the composition of ARGs in the intestinal tract of animals and the effect of nutrients on intestinal ARGs and microbial communities. Reducing antimicrobial resistance and maintaining optimal animal health and performance are urgently needed. Methionine is an essential amino acid which plays a critical role in the growth and reproductive performance of animals. In this study, feeding experiment, in vitro fermentation and bacterial culture experiment were performed to explore the influence of methionine on the intestinal resistome of sows. We found that dietary 0.2 % methionine supplementation decreased the total abundance of intestinal ARGs, which was further confirmed by in vitro fecal microbial fermentation of sows. Metagenome binning analysis identified that Escherichia coli was the major ARG host, which carried 60-113 ARGs and 134-286 virulence factors, indicating that Escherichia coli in the pig intestine is not only a core ARG host, but also an important pathogen. In addition, we found that methionine supplementation inhibited the growth of Escherichia coli, indicating that dietary methionine may reduce the resistome risk in sow intestine by inhibiting core ARG hosts such as Escherichia coli. These findings reveal that dietary methionine application plays a critical role in intestinal antibiotic resistance, providing a new idea for preventing and controlling environmental pollution by antibiotic-resistant microbes.

Dietary Supplementation with Enterococcus faecium R1 Attenuates Intestinal and Liver Injury in Piglets Challenged by Lipopolysaccharide.

In this study, a strain of E. faecium R1 with effective bacteriostatic activity, acid resistance, bile salt resistance, high-temperature resistance was screened. To study the effect of E. faecium R1 on lipopolysaccharide (LPS)-induced intestinal and liver injury in piglets, twenty-four weaned female piglets were randomly assigned into one of three groups (8 piglets per group). Piglets in the control group and LPS group were fed a basal diet, piglets in the E. faecium group were fed the basal diet supplemented with E. faecium R1 (6.5 × 106 CFU/g). On day 21 of the trial, piglets in the LPS group and E. faecium group were intraperitoneally administered LPS (100 µg/kg), piglets in the control group were administered the same volume of saline. Subsequently, blood samples were collected at 3 h, and intestinal, liver, and pancreas samples were collected at 6 h. Results showed that E. faecium R1 supplementation significantly decreased the diarrhea rate and feed to gain ratio, and dramatically reduced LPS-induced intestinal and liver injury in piglets. Compared with the LPS group, E. faecium R1 supplementation significantly increased the content of glucagon in plasma and IL-1ß in the liver, and the mRNA levels of villin in jejunum and ileum and Bcl-xL and pBD-L in the ileum, and significantly decreased the contents of prostaglandin 2 and malondialdehyde in the liver and the activities of myeloperoxidase and aspartate aminotransferase in plasma in piglets. Moreover, E. faecium R1 improved the pancreatic antioxidant capacity in piglets, which was indicated by a significant increase in catalase activity and a decrease in total nitric oxide synthase activity. In summary, dietary supplementation with E. faecium R1 alleviates intestinal and liver injury in LPS-challenged piglets.

Screening for liver X receptor modulators: Where are we and for what use?

Liver X receptors (LXRs) are members of the nuclear receptor superfamily that are canonically activated by oxidized derivatives of cholesterol. Since the mid-90s, numerous groups have identified LXRs as endocrine receptors that are involved in the regulation of various physiological functions. As a result, when their expression is genetically modified in mice, phenotypic analyses reveal endocrine disorders ranging from infertility to diabetes and obesity, nervous system pathologies such Alzheimer's or Parkinson's disease, immunological disturbances, inflammatory response, and enhancement of tumour development. Based on such findings, it appears that LXRs could constitute good pharmacological targets to prevent and/or to treat these diseases. This review discusses the various aspects of LXR drug discovery, from the tools available for the screening of potential LXR modulators to the current situational analysis of the drugs in development. LINKED ARTICLES: This article is part of a themed issue on Oxysterols, Lifelong Health and Therapeutics. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v178.16/issuetoc.