Multi-Enzyme Activity of MIL-101 (Fe)-Derived Cascade Nano-Enzymes for Antitumor and Antimicrobial Therapy.

The clinical application of oncology therapy is hampered by high glutathione concentrations, hypoxia, and inefficient activation of cell death mechanisms in cancer cells. In this study, Fe and Mo bimetallic sulfide nanomaterial (FeS2@MoS2) based on metal-organic framework structure is rationally prepared with peroxidase (POD)-, catalase (CAT)-, superoxide dismutase (SOD)-like activities and glutathione depletion ability, which can confer versatility for treating tumors and mending wounds. In the lesion area, FeS2@MoS2 with SOD-like activity can facilitate the transformation of superoxide anions (O2 -) to hydrogen peroxide (H2O2), and then the resulting H2O2 serves as a substrate for the Fenton reaction with FMS to produce highly toxic hydroxyl radicals (∙OH). Simultaneously, FeS2@MoS2 has an ability to deplete glutathione (GSH) and catalyze the decomposition of nicotinamide adenine dinucleotide phosphate (NADPH) to curb the regeneration of GSH from the source. Thus it can realize effective tumor elimination through synergistic apoptosis-ferroptosis strategy. Based on the alteration of the H2O2 system, free radical production, glutathione depletion and the alleviation of hypoxia in the tumor microenvironment, FeS2@MoS2 NPS can not only significantly inhibit tumors in vivo and in vitro, but also inhibit multidrug-resistant bacteria and hasten wound healing. It may open the door to the development of cascade nanoplatforms for effective tumor treatment and overcoming wound infection.

Liver-derived FGF21 is required for the effect of time-restricted feeding on high-fat diet-induced fatty liver in mice.

Nonalcoholic fatty liver disease (NAFLD), which leads to insulin resistance, steatosis, and even hepatocellular carcinoma, is the most common chronic liver disease worldwide, however, effective treatment is still lacking. This study determined the role of liver FGF21 and the mechanisms underlying the protective effects of time-restricted feeding (TRF) in NAFLD. FGF21 liver knockout (FGF21 LKO) mice and C57BL/6 wild-type (WT) mice were fed either a normal or a high-fat diet (HFD) for 16 weeks. Mice with diet-induced obesity (DIO) were also used. The mice were fed either ad libitum or in a time-restricted manner. Serum FGF21 levels were significantly increased after 16 weeks of TRF. TRF prevented body weight gain, improved glucose homeostasis, and protected against high-fat diet-induced hepatosteatosis and liver damage. The expression of genes related to liver lipogenesis and inflammation was reduced in TRF mice, but the expression of genes involved in fatty acid ß-oxidation was increased. However, those beneficial effects of TRF were blunted in the FGF21 LKO mice. Moreover, TRF promoted improvements in insulin sensitivity and liver damage in DIO mice. Our data show that liver FGF21 signaling was involved in the effect of TRF on high-fat diet-induced fatty liver.

Maternal folic acid and vitamin B12 supplementation during medium to late gestation promotes fetal development via improving placental antioxidant capacity, angiogenesis and amino acid transport.

BACKGROUND: Folic acid and vitamin B12 (FV), being B vitamins, not only facilitate the remethylation of homocysteine (Hcy) but also contribute to embryonic development. This study aimed to assess the impact of FV supplementation during late pregnancy on sows' reproductive performance, amino acid metabolism, placental angiogenesis, and related parameters. Twenty primiparous sows at day 60 of gestation were randomly allocated to two groups: a basal diet (CON) group and a group receiving a basal diet supplemented with folic acid at 20 ppm and vitamin B12 at 125 ppb. RESULTS: The findings revealed that dietary FV supplementation significantly reduced the incidence of intrauterine growth retardation compared to the CON group (P < 0.05). Furthermore, it led to a decrease in the Hcy levels in umbilical cord serum (P < 0.05) and activation of the placental mechanistic target of rapamycin complex 1 (mTORC1) signaling pathway (P < 0.05). Additionally, FV supplementation lowered placental malondialdehyde levels (P < 0.05) and increased the expression of placental thioredoxin (P = 0.05). Moreover, maternal FV supplementation notably elevated placental vascular density (P < 0.05) and the expression of sodium-coupled neutral amino acid transporter 2 (SNAT2) (P < 0.05), as well as amino acid concentrations in umbilical cord blood (P < 0.05). CONCLUSION: Maternal FV supplementation during medium to late gestation reduced Hcy levels in umbilical cord blood and positively impacted fetal development. This improvement was closely associated with increased placental antioxidant capacity and vascular density, as well as activation of the placental mTORC1-SNAT2 signaling pathway. © 2023 Society of Chemical Industry.

Time-Restricted Feeding Ameliorates Uterine Epithelial Estrogen Receptor α Transcriptional Activity at the Time of Embryo Implantation in Mice Fed a High-Fat Diet.

BACKGROUND: More than 30% of reproductive-age women are obese or overweight. Obesity and exposure to a high-fat diet (HFD) detrimentally affect endometrial development and embryo implantation. We previously reported that time-restricted feeding (TRF) improved ovarian follicular development, but whether and how TRF modulates embryo implantation are poorly understood. OBJECTIVE: We investigated the effect of TRF on embryo implantation. METHODS: In TRF group, mice had 10 h of food free access from 9 pm to 7 am, and fed a normal diet or a HFD. Tail vein injection of Chicago blue dye was used to examine embryo implantation sites at day 5.5 (D5.5) of pregnancy. Serum collected at D0.5 and D4.5 of pregnancy was used to examine the level of estradiol (E2) and progesterone. Uterine estrogen receptor (ER) and progesterone receptor levels and their targeted aquaporins (AQPs) were measured. LC-MS was used to analyze bile acid (BA) composition, and primary hepatocytes were used to test the effects of BA on the expression level of SULT1E1, a key enzyme in estrogen inactivation and elimination. RESULTS: We found that TRF prevented HFD-induced embryo loss and alleviated the defect in luminal closure on D4.5 of pregnancy. The cyclic changes of E2 level were lost in mice fed ad libitum but not in TRF mice on the HFD. The HFD increased ER-α expression and transcriptional activity, which induced AQP3 and AQP5 expression on D4.5 of pregnancy. TRF prevented the negative effect of the HFD on uterine luminal closure. Furthermore, in vitro and in vivo results showed that BA suppressed estrogen degradation by activating liver SULT1E1 expression. CONCLUSIONS: Our findings demonstrated that TRF prevented HFD-induced defects in luminal closure, thereby improving embryonic implantation, and provide novel insights into the effects of dietary intervention on obesity and associated infertility.

Acute Endoplasmic Reticulum Stress Suppresses Hepatic Gluconeogenesis by Stimulating MAPK Phosphatase 3 Degradation.

Drug-induced liver injury (DILI) is a widespread and harmful disease, and is closely linked to acute endoplasmic reticulum (ER) stress. Previous reports have shown that acute ER stress can suppress hepatic gluconeogenesis and even leads to hypoglycemia. However, the mechanism is still unclear. MAPK phosphatase 3 (MKP-3) is a positive regulator for gluconeogenesis. Thus, this study was conducted to investigate the role of MKP-3 in the suppression of gluconeogenesis by acute ER stress, as well as the regulatory role of acute ER stress on the expression of MKP-3. Results showed that acute ER stress induced by tunicamycin significantly suppressed gluconeogenesis in both hepatocytes and mouse liver, reduced glucose production level in hepatocytes, and decreased fasting blood glucose level in mice. Additionally, the protein level of MKP-3 was reduced by acute ER stress in both hepatocytes and mouse liver. Mkp-3 deficiency eliminated the inhibitory effect of acute ER stress on gluconeogenesis in hepatocytes. Moreover, the reduction effect of acute ER stress on blood glucose level and hepatic glucose 6-phosphatase (G6pc) expression was not observed in the liver-specific Mkp-3 knockout mice. Furthermore, activation of protein kinase R-like ER kinase (PERK) decreased the MKP-3 protein level, while inactivation of PERK abolished the reduction effect of acute ER stress on the MKP-3 protein level in hepatocytes. Taken together, our study suggested that acute ER stress could suppress hepatic gluconeogenesis by stimulating MKP-3 degradation via PERK, at least partially. Thus, MKP-3 might be a therapeutic target for DILI-related hypoglycemia.

The improvement of parturition duration by high intake of dietary fibre in late gestation is associated with gut microbiota and metabolome in sows.

Prolonged parturition duration has been widely demonstrated to be a risk factor for incidence of stillbirth. This study evaluated the supply of dietary fibre on the parturition duration, gut microbiota and metabolome using sows as a model. A total of 40 Yorkshire sows were randomly given diet containing normal level of dietary fibre (NDF, 17·5 % dietary fibre) or high level of dietary fibre (HDF, 33·5 % dietary fibre). Faecal microbiota profiled with 16S rRNA amplicon sequencing, SCFA and metabolome in the faeces and plasma around parturition were compared between the dietary groups. Correlation analysis was conducted to further explore the potential associations between specific bacterial taxa and metabolites. Results showed that HDF diet significantly improved the parturition process as presented by the shorter parturition duration. HDF diet increased the abundance of the phyla Bacteroidetes and Synergistetes and multiple genera. Except for butyrate, SCFA levels in the faeces and plasma of sows at parturition were elevated in HDF group. The abundances of fifteen and twelve metabolites in the faeces and plasma, respectively, markedly differ between HDF and NDF sows. These metabolites are involved in energy metabolism and bacterial metabolism. Correlation analysis also showed associations between specific bacteria taxa and metabolites. Collectively, our study indicates that the improvement of parturition duration by high fibre intake in late gestation is associated with gut microbiota, production of SCFA and other metabolites, potentially serving for energy metabolism.

Maternal and Fetal Bile Acid Homeostasis Regulated by Sulfated Progesterone Metabolites through FXR Signaling Pathway in a Pregnant Sow Model.

Abnormally elevated circulating bile acids (BA) during pregnancy endanger fetal survival and offspring health; however, the pathology and underlying mechanisms are poorly understood. A total of nineteen pregnant sows were randomly assigned to day 60 of gestation, day 90 of gestation (G60, G90), and the farrowing day (L0), to investigate the intercorrelation of reproductive hormone, including estradiol, progesterone and sulfated progesterone metabolites (PMSs), and BA in the peripheral blood of mother and fetuses during pregnancy. All data were analyzed by Student's t-test or one-way ANOVA of GraphPad Prism and further compared by using the Student-Newman-Keuls test. Correlation analysis was also carried out using the CORR procedure of SAS to study the relationship between PMSs and BA levels in both maternal and fetal serum at G60, G90, and L0. Allopregnanolone sulphate (PM4S) and epiallopregnanolone sulphate (PM5S) were firstly identified in the maternal and fetal peripheral blood of pregnant sows by using newly developed ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) methods. Correlation analysis showed that pregnancy-associated maternal BA homeostasis was correlated with maternal serum PM4S levels, whereas fetal BA homeostasis was correlated with fetal serum PM5S levels. The antagonist activity role of PM5S on farnesoid X receptor (FXR)-mediated BA homeostasis and fibroblast growth factor 19 (FGF19) were confirmed in the PM5S and FXR activator co-treated pig primary hepatocytes model, and the antagonist role of PM4S on FXR-mediated BA homeostasis and FGF19 were also identified in the PM4S-treated pig primary hepatocytes model. Together with the high relative expression of FGF19 in pig hepatocytes, the pregnant sow is a promising animal model to investigate the pathogenesis of cholestasis during pregnancy.

Soy isoflavones supplementation improves reproductive performance and serum antioxidant status of sows and the growth performance of their offspring.

A total of 60 sows (Landrace × Yorkshire, average parity was 1.39) were used to evaluate the effects of soy isoflavones (ISO) supplementation on reproductive performance, serum antioxidant enzyme parameters, and milk compositions of sows, and the growth performance of offspring. Sows were randomly assigned to 4 groups based on the parity. There were 15 replicates per treatment. Dietary treatments were based on a corn-soybean meal-based basal diet and supplemented with 0, 10, 20, or 40 mg/kg ISO. With the increase of the ISO dosage, average daily feed intake of sows increased linearly; oestrus interval decreased linearly and quadratically. In addition, on day 10 of lactation, linear increases in serum superoxide dismutase levels, linear and quadratic increases in serum total antioxidant capacity, and linear decreases in serum malondialdehyde levels were observed in increasing ISO dosage in the diet of sows. The body weight on day 10 and 21 and the average daily gain during days 3-10 and 3-21 of offspring increased linearly at graduated doses of ISO increased. Therefore, feeding sows with graded levels of ISO containing diet during late-gestation and lactation periods improved the reproductive performance of sows and the growth performance of their offspring in a dose-dependent manner.

Arginine promotes testicular development in boars through nitric oxide and putrescine.

The present work aimed to explore the influence and underlying mechanisms involving arginine in testicular development in boars. To this end, thirty 30-day-old male Duroc piglets (7.00 ± 0.30 kg) were randomly sorted into two groups, maintained on either a basal diet (CON, n = 15) or a diet supplemented with 0.8% arginine (ARG, n = 15). Blood and testicular samples were collected during the experimental period to analyse amino acid composition and arginine metabolite levels. The results showed that dietary supplementation with arginine increased number of spermatogonia and height of the seminiferous epithelium (p < 0.05). Sperm density, total number and effective number of sperm of the boars in the ARG group increased significantly compared with those in the CON group (p < 0.05). Although arginine supplementation did not affect plasma amino acid levels, testicular arginine levels in 150-day-old boars exhibited a significant increase (p < 0.05). The level of serum nitric oxide (NO) and activity of nitric oxide synthase (NOS) also increased in 150-day-old boars in the ARG group (p < 0.05). Interestingly, dietary supplementation with arginine increased testicular levels of putrescine in 150-day-old boars (p < 0.05). These results indicated that arginine supplementation increased serum NO levels and testicular arginine and putrescine abundance, thereby improving testicular development and semen quality in boars.

Gut microbial metabolism of dietary fibre protects against high energy feeding induced ovarian follicular atresia in a pig model.

To investigate the effects of dietary fibre on follicular atresia in pigs fed a high-fat diet, we fed thirty-two prepubescent gilts a basal diet (CON) or a CON diet supplemented with 300 g/d dietary fibre (fibre), 240 g/d soya oil (SO) or both (fibre + SO). At the 19th day of the 4th oestrus cycle, gilts fed the SO diet showed 112 % more atretic follicles and greater expression of the apoptotic markers, Bax and caspase-3, and these effects were reversed by the fibre diet. The abundance of SCFA-producing microbes was decreased by the SO diet, but this effect was reversed by fibre treatment. Concentrations of serotonin and melatonin in the serum and follicular fluid were increased by the fibre diet. Overall, dietary fibre protected against high fat feeding-induced follicular atresia at least partly via gut microbiota-related serotonin-melatonin synthesis. These results provide insight into preventing negative effects on fertility in humans consuming a high-energy diet.

Dietary supplementation with Lactobacillus plantarum modified gut microbiota, bile acid profile and glucose homoeostasis in weaning piglets.

Bile acids (BA) have emerged as signalling molecules regulating intestinal physiology. The importance of intestinal microbiota in production of secondary BA, for example, lithocholic acid (LCA) which impairs enterocyte proliferation and permeability, triggered us to determine the effects of oral probiotics on intestinal BA metabolism. Piglets were weaned at 28 d of age and allocated into control (CON, n 14) or probiotic (PRO, n 14) group fed 50 mg of Lactobacillus plantarum daily, and gut microbiota and BA profile were determined. To test the potential interaction of LCA with bacteria endotoxins in inducing damage of enterocytes, IPEC-J2 cells were treated with LCA, lipopolysaccharide (LPS) and LCA + LPS and expressions of genes related to inflammation, antioxidant capacity and nutrient transport were determined. Compared with the CON group, the PRO group showed lower total LCA level in the ileum and higher relative abundance of the Lactobacillus genus in faeces. In contrast, the relative abundances of Bacteroides, Clostridium_sensu_stricto_1, Parabacteroides and Ruminococcus_1, important bacteria genera in BA biotransformation, were all lower in the PRO than in the CON group. Moreover, PRO piglets had lower postprandial glucagon-like peptide-1 level, while higher glucose level than CON piglets. Co-administration of LPS and LCA led to down-regulated expression of glucose and peptide transporter genes in IPEC-J2 cells. Altogether, oral L. plantarum altered BA profile probably by modulating relative abundances of gut microbial genera that play key roles in BA metabolism and might consequently impact glucose homoeostasis. The detrimental effect of LCA on nutrient transport in enterocytes might be aggravated under LPS challenge.

Microbial insight into dietary protein source affects intestinal function of pigs with intrauterine growth retardation.

PURPOSE: Dietary protein, as important macronutrient, is vital for intestinal function and health status. We aimed to determine the effects of dietary protein source on growth performance and intestinal function of neonates with intrauterine growth retardation (IUGR) in a pig model. METHODS: Eighteen pairs of IUGR and normal birth weight (NBW) weaned pigs were allotted to be fed starter diet containing soybean protein concentrate (SPC) or spray-dried porcine plasma (SDPP) for 2 weeks. Growth performance, antioxidant variables, intestinal morphology and absorption capability, microbiota composition and short-chain fatty acids (SCFA) were assessed. RESULTS: IUGR led to poor growth performance, absorption capability and changes on antioxidant variables, while SDPP diet improved the growth performance, diarrhea index, intestinal morphology and antioxidant variables of IUGR or NBW pigs relative to that fed SPC diet. Importantly, SDPP diet improved bacterial diversity and increased the abundance of phylum Firmicutes, but decreased the phylum Proteobacteria in colonic digesta, associating with higher genera Lactobacillus and lower genera Escherichia-Shigella, linking to the increased concentration of SCFA. CONCLUSIONS: Our findings indicate that IUGR impairs the growth rate, intestinal function and oxidative status of weaned pigs, which could be partly improved by SDPP diet either for IUGR or NBW pigs, associating with the better antioxidant capability, composition of microbiotas and their metabolites.

Effects of silymarin supplementation during transition and lactation on reproductive performance, milk composition and haematological parameters in sows.

Silymarin has been shown to be a multiple-functional plant extract having antioxidant, hepatoprotective, hypolipidemic, antihypertensive, antidiabetic and anti-obesity effects. In recent years, the galactagogue effects of silymarin in animals and humans have also been revealed. This research was conducted to test whether dietary inclusion of silymarin during transition and lactation could impact reproductive performance of sows and to explore the underlying mechanisms. From day 108 of gestation to weaning, sows were randomly assigned to receive dietary treatment of silymarin (40 g/day) or not and were designated as control group (CGP, n = 55) or treatment group (TGP, n = 55). The results showed that piglets' average daily gain and average weaning weight were higher in TGP than CGP sows. In comparison with the CGP sows, the TGP sows had higher serum concentrations of catalase (CAT) on day 18 of lactation and glutathione peroxidase (GSH-Px) on day 7 of lactation. The TGP sows had lower concentration of TNF-α on day 7 of lactation and significantly lower concentration of IL-1ß on day 18 of lactation than CGP sows. There was significantly higher serum concentration of PRL on day 7 of lactation in sows consuming silymarin than sows from the CGP group. On day 18 of lactation, the protein and urea contents in milk were significantly increased while the serum urea concentration was significantly decreased in TGP sows. In summary, our results indicate that silymarin supplementation during transition and lactation can increase circulating concentrations of PRL transiently, reduce oxidative stress, increase feed intake and enhance protein metabolism, thereby significantly increasing milk yield of sows and subsequently improving growth performance of their offsprings.

Targeted metabolomics analysis of maternal-placental-fetal metabolism in pregnant swine reveals links in fetal bile acid homeostasis and sulfation capacity.

Cholestasis of pregnancy endangers fetal and neonatal survival, yet systematic knowledge of the cause and effect of disrupted bile acid (BA) homeostasis in pregnancy is limited. Here we show that gestation stage-associated BA dysregulation in swine correlated with fetal death resulting from compromised capacity for BA secretion and increased alternative systemic efflux. The balance of BA input and output in the developing uterus suggested little uptake and metabolism of maternal BA by the placenta-fetus unit, implying a protection role of placenta in preventing maternal BA transported into the fetus. We showed that the maternal origin of BA accounted for the increase in placental total BA, leading to dysregulated expression of genes involved in BA transport and potentially impaired transplacental export of fetus-derived BA. Correspondingly, the secondary BA, mainly derived from the mother, gradually decreased in the fetus. Finally, we identified that sulfation rather than glucuronidation played pivotal roles in maintaining BA homeostasis of the developing fetus. These novel and systemic findings contribute to a whole picture of BA metabolism in pregnancy and provide new insights into mechanisms responsible for maternal and fetal BA homeostasis. NEW & NOTEWORTHY We used a swine model to demonstrate the potentially impaired transplacental bile acid (BA) export, immaturity of fetal hepatic excretory function, and elevated BA synthesis in the developing fetus. Under these conditions, we have further identified that BA sulfation plays a pivotal role in regulation of fetal BA homeostasis, which appears to depend on the balance of BA synthesis and sulfation capacity. These novel findings have uncovered a previously unknown mechanism of BA homeostasis regulation in the developing fetus.

Identification of hepatic fibroblast growth factor 21 as a mediator in 17ß-estradiol-induced white adipose tissue browning.

Both ovarian E2 and hepatic fibroblast growth factor 21 (FGF21) are critical for energy homeostasis and white adipose tissue browning. Estrogen receptor α (ERα) is abundantly expressed in liver. However, whether FGF21 has a role in E2-induced white adipose tissue browning remains uncertain. In this study, we showed that hepatic Fgf21 expression and secretion during estrus cycle changed with the tetradian oscillatory secretion of circulation E2 in adult, female mice, with their peak expressions and secretions at the proestrus. In addition, exogenous E2 robustly stimulated liver Fgf21 expression and elevated serum FGF21 concentrations, which induced browning gene expression and reduced the tissue weight in subcutaneous white adipose in mice with ovariectomies. The inhibitor of mammalian target of rapamycin (mTOR) and of ERα blocked the induction effect of E2 on the expression of Fgf21 in primary hepatocytes, which revealed that E2 might stimulate FGF21 expression via the ERα-mTOR pathway. Furthermore, FGF21 liver-specific deficiency abolished E2-induced white adipose browning in mice with ovariectomies. This study indicates that ovarian E2 increased liver FGF21 expression directly, which in turn, functioned as an endocrine signal to influence inguinal white adipose tissue browning.-Hua, L., Zhuo, Y., Jiang, D., Li, J., Huang, X., Zhu, Y., Li, Z., Yan, L., Jin, C., Jiang, X., Che, L., Fang, Z., Lin, Y., Xu, S., Li, J., Feng, B., Wu, D. Identification of hepatic fibroblast growth factor 21 as a mediator in 17ß-estradiol-induced white adipose tissue browning.

Maternal Dietary Fiber Composition during Gestation Induces Changes in Offspring Antioxidative Capacity, Inflammatory Response, and Gut Microbiota in a Sow Model.

To study the effects of maternal dietary fiber composition during gestation on offspring antioxidant capacity, inflammation, and gut microbiota composition, we randomly assigned 64 gilts to four treatments and administered diets with an insoluble/soluble fiber ratio of 3.89 (R1), 5.59 (R2), 9.12 (R3), and 12.81 (R4). Sow samples (blood and feces at gestation 110) and neonatal samples (blood, liver, and colonic contents) were collected. The results showed that sows and piglets in R1 and R2 had higher antioxidant enzyme activity and lower pro-inflammatory factor levels than those in R3 and R4. Moreover, piglets in R1 and R2 had higher liver mRNA expression of Nrf2 and HO-1 and lower NF-κB than piglets in R4. Interestingly, maternal fiber composition not only affected the production of short-chain fatty acids (SCFAs) in sow feces but also influenced the concentrations of SCFAs in the neonatal colon. Results of high-throughput sequencing showed that piglets as well as sows in R1 and R2 had microbial community structures distinct from those in R3 and R4. Therefore, the composition of dietary fiber in pregnancy diet had an important role in improving antioxidant capacity and decreasing inflammatory response of mothers and their offspring through modulating the composition of gut microbiota.

Interpretation of Fiber Supplementation on Offspring Testicular Development in a Pregnant Sow Model from a Proteomics Perspective.

To study the effects of maternal fiber supplementation during pregnancy on the testicular development of male offspring and its possible mechanisms, 36 sows (Landrace × Yorkshire) were allocated to either a control diet (n = 18) or a fiber diet (the control diet supplemented with 22.60 g/kg inulin and 181.60 g/kg cellulosic; n = 18) during pregnancy. The body and testes weight of the offspring, 7-day-old piglets, was recorded. Testes were collected for further analyses. Results showed that the testicular organ index and the number of spermatogonia in single seminiferous tubule were higher in piglets from the fiber group than from the control group (p < 0.05). In addition, a significant increase in the concentration of glucose, lactate, and lipids in the testes was found in the fiber group (p < 0.05). Proteomic analysis suggested that there were notable differences in glucolipid transport and metabolism, oxidation, and male reproduction-related proteins expression between the two groups (p < 0.05). Results revealed that the most enriched signaling pathways in the fiber group testes included starch and sucrose metabolism, fatty acid metabolism, glutathione metabolism, and the renin-angiotensin system. mRNA expression analyzes further confirmed the importance of some signaling pathways in maternal fiber nutrition regulating offspring testicular development. Our results shed new light on the underlying molecular mechanisms of maternal fiber nutrition on offspring testicular development and provided a valuable insight for future explorations of the effect of maternal fiber nutrition on man reproduction.

Transcriptome Profiling of Placenta through Pregnancy Reveals Dysregulation of Bile Acids Transport and Detoxification Function.

Placenta performs the function of several adult organs for the fetus during intrauterine life. Because of the dramatic physiological and metabolic changes during pregnancy and the strong association between maternal metabolism and placental function, the possibility that variation in gene expression patterns during pregnancy might be linked to fetal health warrants investigation. Here, next-generation RNA sequencing was used to investigate the expression profile, including mRNAs and long non-coding RNAs (lncRNAs) of placentas on day 60 of gestation (G60), day 90 of gestation (G90), and on the farrowing day (L0) in pregnant swine. Bioinformatics analysis of differentially expressed mRNAs and lncRNAs consistently showed dysregulation of bile acids transport and detoxification as pregnancy progress. We found the differentially expressed mRNAs, particularly bile salt export pump (ABCB11), organic anion-transporting polypeptide 1A2 (OATP1A2), carbonic anhydrase II (CA2), Na+-HCO3- cotransporter (NBC1), and hydroxysteroid sulfotransferases (SULT2A1) play an important role in bile acids transport and sulfation in placentas during pregnancy. We also found the potential regulation role of ALDBSSCG0000000220 and XLOC_1301271 on placental SULT2A1. These findings have uncovered a previously unclear function and its genetic basis for bile acids metabolism in developing placentas and have important implications for exploring the potential physiological and pathological pathway to improve fetal outcomes.

Effect of maternal or post-weaning methyl donor supplementation on growth performance, carcass traits, and meat quality of pig offspring.

BACKGROUND: Limited studies have examined links between maternal methyl donor (MET) supplementation and the growth-development characteristics of offspring, and possible underlying mechanisms for such links. This study investigated the effect of maternal or post-weaning MET-supplementation on growth performance, carcass characteristics, and meat quality of the finishing (d 180) offspring. Twenty-four sows were placed on a control (C) or MET-supplemented diet during pregnancy and lactation. Forty-eight female offspring were fed the control or MET-supplemented diet from weaning to 6 months of age, resulting in four study groups (six litters per group): C/C, C/MET, MET/C, and MET/MET. RESULTS: Maternal MET-supplementation increased average daily gain (ADG), body weight (BW), lean percentage and longissimus dorsi (LD) of the offspring at day 180 (P < 0.05), and upregulated the myosin heavy chain IIx, myogenic differentiation and muscle regulatory factor 4 mRNA levels in the LD muscle (P < 0.05). Meanwhile, offspring from maternal MET-supplementation exhibited a higher pH24h post mortem and superoxide dismutase activity, a lower L* 45min , glycolytic potential, malonaldehyde content in the LD muscle, and plasma homocysteine concentration (P < 0.05). CONCLUSION: Maternal MET-supplementation has a remarkable effect on growth performance, carcass traits, and meat quality of the offspring, which is associated with increased expression levels of myogenic genes and anti-oxidant capacity. © 2018 Society of Chemical Industry.

mTORC1 signaling-associated protein synthesis in porcine mammary glands was regulated by the local available methionine depending on methionine sources.

Mechanistic target of rapamycin complex1 (mTORC1) activation and protein synthesis varied with methionine sources; however, the related mechanisms are largely unknown. Porcine mammary epithelial cells (PMEC) and mammary tissue slices (MTS) were used to test whether methionine precursors differ in providing the available methionine and thus differ in mTORC1 signaling-associated protein synthesis. PMEC with methionine deprivation for 8 h and MTS from lactating sows were cultured for 24 and 2 h, respectively, with treatment media without methionine (negative control, NC) or supplemented with 0.6 mM (for PMEC) and 0.1 mM (for MTS) of L-methionine (L-MET), D-methionine (D-MET), DL-2-hydroxy-4-(methylthio) butyric acid (HMTBA), or keto-methyl(thio)butanoic acid (KMB). The measurements included: phosphorylation of mTORC1 signaling, fractional protein synthesis rate (FSR), amino acids (AA) profile, and enzyme activities. Compared with the NC treatment, activated mTORC1 signaling as manifested by higher (P < 0.05) protein abundance of phosphorylated-S6 Kinase 1 (P-S6K1) and phosphorylated-4E-binding Protein 1 (P-4E-BP1) in PMEC and MTS, and increased protein synthesis as indicated by higher (P < 0.05) FSR in MTS occurred in L-MET and HMTBA treatments rather than in D-MET treatment. Compared with the NC treatment, methionine concentration and ratio of methionine to lysine in MTS increased (P < 0.05) in L-MET and HMTBA treatments but not in D-MET treatment, and activities of enzymes responsible for conversion of D-MET and HMTBA to keto-methionine in mammary tissues were about 10 and 50%, respectively, of that in liver. Taken together, mTORC1 signaling-associated protein synthesis in porcine mammary glands was regulated by the local available methionine depending on methionine sources.