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.

Temporal gene expression profiling during early-stage traumatic temporomandibular joint bony ankylosis in a sheep model.

BACKGROUND: Investigating the molecular biology underpinning the early-stage of traumatic temporomandibular joint (TMJ) ankylosis is crucial for discovering new ways to prevent the disease. This study aimed to explore the dynamic changes of transcriptome from the intra-articular hematoma or the newly generated ankylosed callus during the onset and early progression of TMJ ankylosis. METHODS: Based on a well-established sheep model of TMJ bony ankylosis, the genome-wide microarray data were obtained from samples at postoperative Days 1, 4, 7, 9, 11, 14 and 28, with intra-articular hematoma at Day 1 serving as controls. Fold changes in gene expression values were measured, and genes were identified via clustering based on time series analysis and further categorised into three major temporal classes: increased, variable and decreased expression groups. The genes in these three temporal groups were further analysed to reveal pathways and establish their biological significance. RESULTS: Osteoblastic and angiogenetic genes were found to be significantly expressed in the increased expression group. Genes linked to inflammation and osteoclasts were found in the decreased expression group. The various biological processes and pathways related to each temporal expression group were identified, and the increased expression group comprised genes exclusively involved in the following pathways: Hippo signaling pathway, Wnt signaling pathway and Rap 1 signaling pathway. The decreased expression group comprised genes exclusively involved in immune-related pathways and osteoclast differentiation. The variable expression group consisted of genes associated with DNA replication, DNA repair and DNA recombination. Significant biological pathways and transcription factors expressed at each time point postoperatively were also identified. CONCLUSIONS: These data, for the first time, presented the temporal gene expression profiling and reveal the important process of molecular biology in the early-stage of traumatic TMJ bony ankylosis. The findings might contributed to identifying potential targets for the treatment of TMJ ankylosis.

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.

Hepatic-Specific FGF21 Knockout Abrogates Ovariectomy-Induced Obesity by Reversing Corticosterone Production.

Increased glucocorticoid (GC) levels act as a master contributor to central obesity in estrogen-depleted females; however, what factors cause their increased GC production is unclear. Given (1) liver fibroblast growth factor 21 (FGF21) and GCs regulate each other's production in a feed-forward loop, and (2) circulating FGF21 and GCs are parallelly increased in menopausal women and ovariectomized mice, we thus hypothesized that elevation of hepatic FGF21 secretion causes increased GGs production in estrogen-depleted females. Using the ovariectomized mice as a model for menopausal women, we found that ovariectomy (OVX) increased circulating corticosterone levels, which in turn increased visceral adipose Hsd11b1 expression, thus causing visceral obesity in females. In contrast, liver-specific FGF21 knockout (FGF21 LKO) completely reversed OVX-induced high GCs and high visceral adipose Hsd11b1 expression, thus abrogating OVX-induced obesity in females. Even though FGF21 LKO failed to rescue OVX-induced dyslipidemia, hepatic steatosis, and insulin resistance. What's worse, FGF21 LKO even further exacerbated whole-body glucose metabolic dysfunction as evidenced by more impaired glucose and pyruvate tolerance and worsened insulin resistance. Mechanically, we found that FGF21 LKO reduced circulating insulin levels, thus causing the dissociation between decreased central obesity and the improvement of obesity-related metabolic syndromes in OVX mice. Collectively, our results suggest that liver FGF21 plays an essential role in mediating OVX-induced central obesity by promoting GC production. However, lack of liver FGF21 signaling reduces insulin production and in turn causes the dissociation between decreased central obesity and the improvement of obesity-related metabolic syndromes, highlighting a detrimental role for hepatic FGF21 signals in mediating the development of central obesity but a beneficial role in preventing metabolic abnormality from further exacerbation in estrogen-depleted females.

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.

RNA-seq coupling two different methods of castration reveals new insights into androgen deficiency-caused degeneration of submaxillary gland in male Sprague Dawley rats.

BACKGROUND: Salivary gland (SMG) degeneration and dysfunction are common symptoms that occur after sex hormone deprivation, but the underlying mechanisms remain largely unknown. Additionally, immunocastration, which causes drop of sex hormones, has been developed as an alternative to surgical castration, however whether it exerts similar effects as surgical castration on the salivary glands is unknown. Through histological and RNA-seq analysis, we assessed changes in morphology and transcriptome of SMG in response to immunocastration (IM) versus surgical castration (bilateral orchiectomy, ORC). RESULTS: Compared to entire males (EM), ORC caused severe degeneration of SMG in rats, as evidenced by both decreased (P < 0.01) SMG weight and organ index, and by decreased (P < 0.01) quantity of SMG acini and ducts. IM had minimal effects (P > 0.05) on SMG weight and organ index, but it still caused degeneration (P < 0.05) of the acini and ducts. Even though, the quantity of both SMG acini and ducts was much higher (P < 0.001) in IM than in ORC. Functional enrichment analysis of the common regulated genes by ORC/IM revealed disrupted epithelial cell development, angiogenesis, anatomical structure morphogenesis and enhanced cell death are associated with SMG degeneration in deprivation of androgens. Integrated data analysis shown that there existed a selective hyperfunction of SMG ribosome and mitochondrion in ORC but not in IM, which might be associated with more severe degeneration of SMG in ORC than in IM. CONCLUSIONS: Our findings suggested that both surgical castration and immunocastration caused SMG degeneration by disrupting epithelial cell development, angiogenesis, anatomical structure morphogenesis and enhancing cell death. But, surgical castration selectively induced hyperfunction of SMG ribosome and mitochondrion, thus causing more severe degeneration of SMG than immunocastration.

Two Synthetic Peptides Corresponding to the Human Follicle-Stimulating Hormone ß-Subunit Promoted Reproductive Functions in Mice.

A follicle stimulating hormone (FSH) is widely used in the assisted reproduction and a synthetic peptide corresponding to a receptor binding region of the human (h) FSH-ß-(34−37) (TRDL) modulated reproduction. Furthermore, a 13-amino acid sequence corresponding to hFSH-ß-(37−49) (LVYKDPARPKIQK) was recently identified as the receptor binding site. We hypothesized that the synthetic peptides corresponding to hFSH-ß-(37−49) and hFSH-ß-(34−49), created by merging hFSH-ß-(34−37) and hFSH-ß-(37−49), modulate the reproductive functions, with the longer peptide being more biologically active. In male or female prepubertal mice, a single injection of 200 µg/g BW ip of hFSH-ß-(37−49) or hFSH-ß-(34−49) hastened (p < 0.05) puberty, whereas the same treatments given daily for 4 d promoted (p < 0.05) the gonadal steroidogenesis and gamete formation. In addition of either peptide to the in vitro cell cultures, promoted (p < 0.05) the proliferation of primary murine granulosa cells and the estradiol production by upregulating the expression of Ccnd2 and Cyp19a1, respectively. In adult female mice, 200 µg/g BW ip of either peptide during diestrus antagonized the FSH-stimulated estradiol increase and uterine weight gain during proestrus. Furthermore, hFSH-ß-(34−49) was a more potent (p < 0.05) reproductive modulator than hFSH-ß-(37−49), both in vivo and in vitro. We concluded that hFSH-ß-(37−49) and especially hFSH-ß-(34−49), have the potential for reproductive modulation.

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.

Association of three SNPs in adiponectin gene with lipid traits of Tianzhu Black Muscovy (Cairina moschata).

Adiponectin plays a critically biological role in atherosclerosis, glucose utilization, lipid and carbohydrate metabolism, and triglyceride synthesis in animals and humans. However, little is known about the effect of adiponectin on lipid metabolism of the avian species. The aim of the preset study was to investigate the potential associations between adiponectin gene single nucleotide polymorphisms (SNPs) and the lipid traits in 348 females of Tianzhu Black Muscovy. Three novel SNPs (167G>A, 290T>C and 711G>A) were detected in adiponectin gene. 167G>A and 290T>C has linked very closely, and then 711G>A with 167G>A and 290T>C has no strong linkage disequilibrium, respectively. The Chi square test showed that allelic frequency and genotype frequency of two SNPs (167G>A and 711G>A) didn't agree with the Hardy-Weinberg equilibrium (P>0.05). Four haplotypes and nine diplotypes were formed on the three SNPs of adiponectin gene. Association analysis indicated that the 167G>A genotypes were strongly associated with intramuscular fat (IMF) of chest muscle and serum total cholesterol (TC) (P < 0.01); the 290T>C genotypes were strongly associated with IMF, TC, and serum triglyceride (TG) (P < 0.01); furthermore, the 711G>A genotypes were significantly associated with TG and TC (P < 0.05); the diplotypes were strongly associated with IMF, TC, and TG (P < 0.01). Therefore, three SNPs in adiponectin were potential markers for improving IMF in Muscovy ducks.

Preserving the Fibrous Layer of the Mandibular Condyle Reduces the Risk of Ankylosis in a Sheep Model of Intracapsular Condylar Fracture.

PURPOSE: The aim of this experimental study was to investigate the role of the fibrous layer of the condylar head in the formation of temporomandibular joint (TMJ) ankylosis in a sheep model of intracapsular condylar fracture. MATERIALS AND METHODS: Six growing Xiao-wei Han sheep were used in the study, and bilateral TMJ surgery was performed in each sheep. In the left TMJ, sagittal fracture of the condyle, removal of the fibrous layer of the condylar head, excision of two thirds of the disc, and removal of the fibrous zone of the glenoid fossa were performed. In the right TMJ, the same surgical management was performed, except that in each sheep, the fibrous layer of the condylar head was preserved. Three sheep were killed humanely at 1 month postoperatively, and the other 3 sheep were killed humanely at 3 months postoperatively. The TMJ complexes were examined by histologic evaluation. RESULTS: Fibrous ankylosis was observed on the left side in 3 sheep at 1 month postoperatively and in 2 of 3 sheep at 3 months postoperatively. Fibro-osseous ankylosis was achieved on the left side in 1 sheep at 3 months postoperatively. In the right TMJ, the main postoperative histologic findings included condylar fracture healing, topical rupture or exfoliation of the fibrous layer of the condyle, and fissure between the fibrous layer and the proliferative zone of the condyle. However, no evidence of ankylosis was observed. The TMJ ankylosis scores on the right side were significantly lower than those on the left side at different time points (P < .05). CONCLUSIONS: This study showed that the presence of the fibrous layer of the condylar head prevented the development of TMJ ankylosis in a sheep model of intracapsular condylar fracture.

Endoplasmic Reticulum Stress Inducer Tunicamycin Alters Hepatic Energy Homeostasis in Mice.

Disorders of hepatic energy metabolism, which can be regulated by endoplasmic reticulum (ER) stress, lead to metabolic diseases such as hepatic steatosis and hypoglycemia. Tunicamycin, a pharmacological ER stress inducer, is used to develop an anti-cancer drug. However, the effects of tunicamycin on hepatic energy metabolism have not been well elucidated. Mice were intraperitoneally injected with tunicamycin or vehicle. Twenty-four hours later, hepatic triglyceride and glycogen content and serum lipids profiles were analyzed, as well as the expression of lipogenic and gluconeogenic genes. Tunicamycin significantly induced hepatic a yellowish color and ER stress, as well as increasing serum levels of aspartate transaminase and alanine transaminase. Besides, tunicamycin remarkably increased hepatic triglyceride content and suppressed the expression of apolipoprotein B100. In addition, tunicamycin-treated mice had lower serum levels of triglyceride, apolipoprotein B, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol. Gene expression of peroxisome proliferator-activated receptor α was decreased by tunicamycin, but the protein level was increased. Furthermore, blood glucose level and hepatic glycogen content were decreased in tunicamycin-treated mice. Protein kinase B signaling was attenuated in the tunicamycin-treated liver, but the expression and activities of phosphoenolpyruvate carboxykinase and glucose-6-phosphatase were unchanged. Tunicamycin alters hepatic energy homeostasis by increasing triglyceride accumulation and decreasing glycogen content.

Dietary supplementation with ß-hydroxy-ß-methylbutyrate calcium during the early postnatal period accelerates skeletal muscle fibre growth and maturity in intra-uterine growth-retarded and normal-birth-weight piglets.

Intra-uterine growth restriction (IUGR) impairs postnatal growth and skeletal muscle development in neonatal infants. This study evaluated whether dietary ß-hydroxy-ß-methylbutyrate Ca (HMB-Ca) supplementation during the early postnatal period could improve muscle growth in IUGR neonates using piglets as a model. A total of twelve pairs of IUGR and normal-birth-weight (NBW) male piglets with average initial weights (1·85 (sem 0·36) and 2·51 (sem 0·39) kg, respectively) were randomly allotted to groups that received milk-based diets (CON) or milk-based diets supplemented with 800 mg/kg HMB-Ca (HMB) during days 7-28 after birth. Blood and longissimus dorsi (LD) samples were collected and analysed for plasma amino acid content, fibre morphology and the expression of genes related to muscle development. The results indicate that, regardless of diet, IUGR piglets had a significantly decreased average daily weight gain (ADG) compared with that of NBW piglets (P<0·05). However, IUGR piglets fed HMB-Ca had a net weight and ADG similar to that of NBW piglets fed the CON diet. Irrespective of body weight (BW), HMB-Ca supplementation markedly increased the type II fibre cross-sectional area and the mRNA expression of mammalian target of rapamycin (mTOR), insulin-like growth factor-1 and myosin heavy-chain isoform IIb in the LD of piglets (P<0·05). Moreover, there was a significant interaction between the effects of BW and HMB on mTOR expression in the LD (P<0·05). In conclusion, HMB-Ca supplementation during the early postnatal period could improve skeletal muscle growth and maturity by accelerating fast-twitch glycolytic fibre development in piglets.

Amino acid standardized ileal digestibility together with concentrations of digestible and metabolizable energy in Saccharomyces cerevisiae yeast and soybean meal for gestating sows.

The standardized ileal digestibility (SID) of amino acids (AAs) plus crude protein (CP), in addition to digestible energy (DE) and metabolizable energy (ME) concentrations, was assessed through two experiments on Saccharomyces cerevisiae yeast (SCY) combined with soybean meal (SBM) for gestating sows. SCY and SBM were subjected to experiment 1 for the determination of CP and AAs in terms of SID. Under a randomized complete block design, three dietary treatments were provided for a total of 24 Landrace × Yorkshire gestating sows (parity 2), with the distal ileum clipped by a T-cannula at gestational day 33 based on body weight (BW) (194.1 ±â€…7.1, 195.3 ±â€…8.5, and 195.3 ±â€…8.6 kg). SCY and SBM were used as the only source of nitrogen to prepare two semi-purified diets and a nitrogen-free diet was also utilized to examine CP plus AAs for basal ileal endogenous losses. The gestating sows were initially fed these diets for 5 d to allow for adaptation, and ileal digesta was collected 2 d later for analysis. CP and all AAs in SCY, except for Trp and Gly, showed significantly lower SID than those in SBM (P < 0.05). Among the essential AAs, the range of SID was 68.8% for Thr to 92.2% for Arg in dried yeast, and from 79.9% for Thr to 98.6% for Met in SBM. DE plus ME were measured via experiment 2 with a randomized complete block design on SCY and SBM. Eighteen day-35 Landrace × Yorkshire pregnant sows (parity 3) were allocated to three diets based on BW (233.3 ±â€…16.0, 233.4 ±â€…9.6, and 233.4 ±â€…10.3 kg). Three diets were adopted for the experiment, namely, a corn-based diet as well as two diets containing 20.2% SCY and 20.0% SBM samples. The full fecal collection method, comprising a 5-day adaptation period before a 5- to 6-d experimental period for quantitative urine and feces collection, was employed for metabolic trials. The DE and ME for SCY were remarkably decreased compared with those for SBM (3812 kcal/kg DM vs. 4264 kcal/kg DM and 3714 kcal/kg DM vs. 4157 kcal/kg DM), respectively (P < 0.05). No differences were observed in the apparent total tract digestibility (ATTD) of organic matter, CP, and gross energy between SCY and SBM, but ATTD was significantly reduced in SCY for acid detergent fiber, dry matter, and neutral detergent fiber by contrast with SBM (P < 0.05). In conclusion, most AAs and CP in SCY had lower SID, DE, and ME than SBM in this study. These findings can be applied to diet formulation with the aforementioned ingredients for sows.

Saccharomyces cerevisiae yeast (SCY) is commonly used as an additive in feed (<1% of the formulation), but there is a limited amount of available information about its function as a promising source of proteins for pig diets, and especially, the nutritive value of yeast protein for gestating sows remains to be clarified. Feeding stuff has different digestibility between growing and gestating pigs. Therefore, our study evaluated the standardized ileal digestibility of amino acids and crude protein together with metabolizable and digestible energy in SCY for gestating sows, to provide nutritional value parameters on its potential as an effective alternative to traditional protein ingredients such as soybean meal in sow diet formulations.

Effects of maternal methyl donor intake during pregnancy on ileum methylation and function in an intrauterine growth restriction pig model.

BACKGROUND: Intrauterine growth retardation (IUGR) affects intestinal growth, morphology, and function, which leads to poor growth performance and high mortality. The present study explored whether maternal dietary methyl donor (MET) supplementation alleviates IUGR and enhances offspring's growth performance by improving intestinal growth, function, and DNA methylation of the ileum in a porcine IUGR model. METHODS: Forty multiparous sows were allocated to the control or MET diet groups from mating until delivery. After farrowing, 8 pairs of IUGR and normal birth weight piglets from 8 litters were selected for sampling before suckling colostrum. RESULTS: The results showed that maternal MET supplementation tended to decrease the IUGR incidence and increased the average weaning weight of piglets. Moreover, maternal MET supplementation significantly reduced the plasma concentrations of isoleucine, cysteine, urea, and total amino acids in sows and newborn piglets. It also increased lactase and sucrase activity in the jejunum of newborn piglets. MET addition resulted in lower ileal methionine synthase activity and increased betaine homocysteine S-methyltransferase activity in the ileum of newborn piglets. DNA methylation analysis of the ileum showed that MET supplementation increased the methylation level of DNA CpG sites in the ileum of newborn piglets. Down-regulated differentially methylated genes were enriched in folic acid binding, insulin receptor signaling pathway, and endothelial cell proliferation. In contrast, up-regulated methylated genes were enriched in growth hormone receptor signaling pathway and nitric oxide biosynthetic process. CONCLUSIONS: Maternal MET supplementation can reduce the incidence of IUGR and increase the weaning litter weight of piglets, which may be associated with better intestinal function and methylation status.

Microbial Mechanistic Insight into the Role of Yeast-Derived Postbiotics in Improving Sow Reproductive Performance in Late Gestation and Lactation Sows.

The purpose of this study is to investigate the effects of supplementing Yeast-derived postbiotics (Y-dP) to the diet of sows during late pregnancy and lactation on fecal microbiota and short-chain fatty acids (SCFA) in sows and their offspring weaned piglets, as well as the relationship between gut microbiota and SCFA, serum cytokines, and sow reproductive performance. A total of 150 sows were divided into three groups: control diet (CON), CON + Y-dP 1.25 g/kg, and CON + Y-dP 2 g/kg. The results showed that supplementing 0.125% Y-dP to the diet of sows can increase the content of isobutyric acid (IBA) in the feces of pregnant sows and reduce the content of butyric acid (BA) in the feces of weaned piglets (p < 0.05). The fecal microbiota of pregnant sows ß diversity reduced and piglet fecal microbiota ß diversity increased (p < 0.05). Y-dP significantly increased the abundance of Actinobacteria and Limosilactobacilli in the feces of pregnant sows (p < 0.05), as well as the abundance of Verrucomicrobiota, Bacteroidota, and Fusobacteriota in the feces of piglets (p < 0.05). The abundance of Bacteroidota in the feces of pregnant sows is positively correlated with propionic acid (PA) (r > 0.5, p < 0.05). The abundance of Prevotellaceae_NK3B31_group was positively correlated with Acetic acid (AA), PA, Valerate acid (VA), and total volatile fatty acid (TVFA) in the feces of pregnant sows (r > 0.5, p < 0.05), and Bacteroidota and Prevotellaceae_NK3B31_group were negatively correlated with the number of stillbirths (r < -0.5, p < 0.05). The abundance of Lactobacillus and Holdemanella in piglet feces was positively correlated with TVFA in feces and negatively correlated with IgA in serum (r > 0.5, p < 0.05). In conclusion, supplementing Y-dP to the diet of sows from late gestation to lactation can increase the chao1 index and α diversity of fecal microorganisms in sows during lactation, increase the abundance of Actinobacteria and Limosilactobacilli in the feces of sows during pregnancy, and increase the abundance of beneficial bacteria such as Bacteroidetes in piglet feces, thereby improving intestinal health. These findings provide a reference for the application of Y-dP in sow production and a theoretical basis for Y-dP to improve sow production performance.

Bile acids metabolism in the gut-liver axis mediates liver injury during lactation.

AIMS: The obesity epidemic, especially in pregnant women, linked to a higher risk of liver diseases. Bile acids (BAs) are known to participate in liver metabolism, but this function during obesogenic reproductive process remains largely uncertain. The study aims to identify whether a high-fat diet (HFD) during pregnancy negatively disturbs liver metabolism and the potential role of BAs and gut microbiota (GM)in a sow model. MAIN METHODS: Reproductive (RP) or non-reproductive (NRP) sows were fed a 15 % HFD containing compound oil. Body condition, blood parameters, and BAs levels/profile during gestation and lactation were monitored. The tissues and colonic GM were collected after euthanasia at the end of lactation. HepG2 hepatocytes were used to test the effects of BAs on liver damage and the mechanism. KEY FINDINGS: Reproductive sows fed an HFD (HF-RP) experienced increased weight loss, and elevated plasma non-esterified fatty acid (NEFA) during lactation, consistent with exacerbated lipolysis, aggravating the risk of liver damage. HF-RP sows exhibited an enlarged BAs pool size and alterations in composition (higher levels of CDCA and LCA species) along with a drastic change in the GM (increased Firmicutes/Bacteroidetes ratio and declined Lactobacillus abundance). Furthermore, the liver FXR-SHP pathway, BAs synthesis and transport underwent adaptive regulation to sustain the BAs homeostasis and hepatic lipid metabolism. CDCA alleviated endoplasmic reticulum (ER) stress induced by palmitic acid via FXR pathway, in HepG2 cells. SIGNIFICANCE: Lactation BAs metabolism signal in gut-liver axis coordinated the risk of liver damage induced by exacerbated lipolysis in obesogenic pregnancy.

Generation of Porcine Angiogenin 4-Expressing Pichia pastoris and Its Protection against Intestinal Inflammatory Injury.

Antimicrobial peptides have been extensively studied as potential alternatives to antibiotics. Porcine angiogenin 4 (pANG4) is a novel antimicrobial peptide in the angiogenin (ANG) family, which may have a regulatory effect on intestinal microflora. The object of present study is obtained pANG4 protein by heterologous expression, so as to explore the biological function of recombinant pANG4 (rpANG4). The pANG4 was expressed in Pichia pastoris (P. pastoris) and anti-inflammatory effects were investigated in intestinal porcine epithelial cell line-J2 (IPEC-J2) and mice. Purified rpANG4 had bacteriostatic activity and did not cause hemolysis or cytotoxicity at concentrations below 128 µg/mL. Purified rpANG4 increased the activity of IPEC-J2 and reduced apoptosis in vitro. rpANG4 reduced the pro-inflammatory gene expression and upregulated tight junction protein gene expression during inflammation. rpANG4 alleviated lipopolysaccharide (LPS)-induced liver and spleen damage, intestinal inflammation, jejunal apoptosis genes' expression, and improved immune function in an in vivo mice model. rpANG4 increased tight junction protein gene expression in jejunum, thereby improving the jejunum intestinal barrier function. In conclusion, rpANG4 had antibacterial activity, inhibited intestinal inflammation, improved intestinal barrier function, and alleviated liver and spleen damage. The current study contributes to the development of antibiotic substitutes and the improvement of animal health.

Revealing the mechanism of fiber promoting sow embryo implantation by altering the abundance of uterine fluid proteins: A proteomic perspective.

Many studies have shown that fiber in the diet plays an important role in improving the reproductive performance of sows, but there is rarely research on the impact of fiber on early embryo implantation. This study used 4D-Label free technology to identify and analyze the effect of the fiber composition in the diet on the protein in the early pregnancy uterine fluid (UF) of sows. The results indicate that ratio of insoluble fibers to soluble fibers (ISF/SF) 4.89 can increase the concentration of progesterone (PROG) and reduce tumor necrosis factorα (TNF-α) concentration in sow UF. In addition, through 4D-Label free, we identified a total of 4248 proteins, 38 proteins abundance upregulated and 283 proteins abundance downregulated in UF. Through enrichment analysis of these differential abundance proteins (DAPs), it was found that these differential proteins are mainly related to the docking of extracellular vesicles, vesicular transport, inflammatory response, and insulin resistance. Therefore, the results of this study reveal the possible mechanism by which fiber improves the reproductive performance of sows, laying a theoretical foundation for future research on the effects of diet on reproduction. SIGNIFICANCE: This study demonstrates the importance of dietary fiber for early embryo implantation in sows. The effect of dietary ISF/SF on early embryo implantation in sows was elucidated from a proteomic perspective through 4D-Label free technology. This study not only has significant implications for improving sow reproductive efficiency, but also provides important theoretical references for studying early miscarriage and reproductive nutrition in human pregnancy.

Standardized ileal digestibility of amino acids in Chinese fermented soybean meal from different sources fed to mid and late-gestating sows.

We determined apparent ileal digestibility (AID) and standardized ileal digestibility (SID) values of crude protein (CP) and amino acids (AA) in fermented soybean meal from five different sources (FSBM 1 to 5) in China when fed to mid and late-gestating sows. Twenty-four parity four sows (12 at 30 d in gestation and 12 at 80 d in gestation) were fitted with a T-cannula in the distal ileum and used in this experiment. Sows were randomly assigned to a replicated 6 × 3 Youden square design including six diets and three periods. Six diets were provided for sows in mid and late gestation, including a nitrogen-free diet and five test diets containing 26% FSBM from different sources. Results showed that there were differences in AID and SID of CP among the different FSBM samples, but no differences between sow physiological stages were observed. Specifically, when mid-gestating sows were fed FSBM 2, the AID of CP was the lowest, whereas FSBM 3 exhibited a greater AID of CP when compared to the other FSBM samples (P < 0.01). Furthermore, during late gestation, FSBM 3 consistently had greater SID of CP when compared to other FSBM samples (P < 0.01). The ileal digestibility of most AA varied with different FSBM samples. In both mid and late gestation, differences (P < 0.05) were observed for AID of lysine, tryptophan, histidine, and arginine across different FSBM samples. Similarly, the AID of dispensable AA (cysteine, glutamine, and serine) also exhibited differences (P < 0.05) across different FSBM samples in both mid and late-gestating sows. For mid-gestating sows, SID differences relating to lysine, phenylalanine, tryptophan, threonine, and arginine were observed among different diets (P < 0.05). In late-gestating sows, SID values for lysine, tryptophan, leucine, and arginine differed across diets (P < 0.05). Furthermore, the ileal digestibility of some dispensable AA was influenced by physiological stage, as evidenced by greater AID and SID values for glycine, glutamine, cysteine, and serine in late-gestating sows when compared to mid-gestating sows (P < 0.01). In summary, our study determined AA ileal digestibility of different FSBM fed to mid and late-gestating sows. We observed that the AA ileal digestibility differed among five FSBM samples, but the physiological stage of sows did not affect the ileal digestibility of CP and most AA. Additionally, when formulating diets for sows, it is crucial to consider the nutritional value differences of FSBM.

Fermented soybean meal (FSBM) is obtained from the microbial fermentation of soybean meal, which reduces anti-nutritional factor levels and enhances other nutrient content. Substituting soybean meal with FSBM in piglet and growing pig diets improves nutrient digestibility. However, its nutritional value for sows remains unclear. Therefore, five sources of FSBM were fed to sows in mid and late gestation to evaluate apparent ileal digestibility (AID) and standardized ileal digestibility (SID) values of amino acids (AA). We found that different FSBM samples impacted the SID value of AA when fed to gestating sows. Additionally, sow physiological stage influenced the SID of some dispensable AA. These findings provide valuable insights into the incorporation of FSBM into sow diets.

Benefits of maternal pectin supplementation in gestation diet on vaginal microbiota of sows and intestinal health of newborn piglets.

Pectin is a proven prebiotic and widely used in human health products. This study aims to assess the impact of dietary pectin supplementation during gestation on sow vaginal microbiota and the offspring's intestinal composition. Thirty sows were randomly allocated to two groups and fed a standard diet (CON) or a standard diet supplemented with 3 g/kg pectin (PEC). Blood, feces, and vaginal swab samples from the sows and blood, intestines issue, and colonic content samples from the offspring were collected and analyzed. The results indicate that the relative abundance of vaginal Lactobacillus was notably enhanced in the PEC group and fecal ß-glucuronidase (ß-G) activity and plasma 17ß-estradiol (E2) concentration were also significantly increased in the PEC group. Newborn piglets were found to host different microbial communities as well. At the phylum level, Proteobacteria dominated in the CON group, and Firmicutes was predominant in the PEC group. Newborn piglets in the PEC group had a lower interleukin-6 (IL-6) concentration in their plasma. The expression of intestinal cytokines of offspring was improved as well. Villus height and villus height/crypt depth (V/C) in the PEC group were extremely higher than those in the CON group. In conclusion, dietary pectin supplementation can be of benefit to both sows and newborn piglets.