Maternal or post-weaning dietary fructo-oligosaccharide supplementation reduces stillbirth rate of sows and diarrhea of weaned piglets.

Fructo-oligosaccharides (FOS) are well-known prebiotics that have the potential to improve sow reproductive performance and increase piglet growth. However, previous studies were observed in sole FOS-supplemented diets of sows or weaned piglets and did not consider the sow-to-piglet transfer effect on the performance and diarrhea rate of weaned piglets. This study explores the effects of dietary FOS supplementation on the reproductive performance of sows, and the effects of FOS supplementation at different stages on the growth performance and diarrhea rate of weaned piglets. A split-plot experimental design was used with sow diet effect in the whole plot and differing piglet diet effect in the subplot. Fifty-two multiparous sows (223.24 ± 14.77 kg) were randomly divided into 2 groups (0 or 0.2% FOS). The experiment lasted from day 85 of gestation to day 21 of lactation. Reproductive performance, glucose tolerance, placental angiogenesis, and intestinal flora of sows were assessed. At weaning, 192 weaned piglets were grouped in 2 × 2 factorial designs, with the main effects of FOS supplemental level of sow diet (0 and 0.2%), and FOS supplemental level of weaned piglet diet (0 and 0.2%), respectively. The growth performance and diarrhea rate of the weaned piglets were analyzed during a 28-d experiment. Maternal dietary supplementation of FOS was shown to reduce the stillbirth and invalid piglet rates (P < 0.05), improve the insulin sensitivity (P < 0.05) and fecal scores (P < 0.05) of sows, increase the abundance of Akkermansia muciniphila (P = 0.016), decrease the abundance of Escherichia coli (P = 0.035), and increase the isovalerate content in feces (P = 0.086). Meanwhile, the placental angiogenesis marker CD31 expression was increased in sows fed FOS diet (P < 0.05). Moreover, maternal and post-weaning dietary FOS supplementation reduced the diarrhea rate of weaned piglets (P < 0.05) and increased the content of short-chain fatty acids in feces (P < 0.05). Furthermore, only post-weaning dietary FOS supplementation could improve nutrient digestibility of weaned piglets (P < 0.05). Collectively, FOS supplementation in sows can reduce stillbirth rate, perinatal constipation, and insulin resistance, as well as improve placental vascularization barrier. Additionally, maternal and post-weaning dietary FOS supplementation reduced the diarrhea rate of weaned piglets, but only FOS supplementation in piglets alone at weaning stage could improve their nutrient digestibility.

Effects of dietary iron supplementation on reproductive performance of sows and growth performance of piglets.

This experiment aimed to investigate the effects of dietary iron supplementation from different sources on the reproductive performance of sows and the growth performance of piglets. A total of 87 sows with similar farrowing time were blocked by body weight at day 85 of gestation, and assigned to one of three dietary treatments (n = 29 per treatment): basal diet, basal diet supplemented with 0.2% ferrous sulfate (FeSO4), and basal diet supplemented with 0.2% iron sucrose, respectively, with 30% iron in both FeSO4 and iron sucrose. Compared with the control (CON) group, iron sucrose supplementation reduced the rate of stillbirth and invalid of neonatal piglets (P < 0.05), and the number of mummified fetuses was 0. Moreover, it also improved the coat color of newborn piglets (P < 0.05). At the same time, the iron sucrose could also achieve 100% estrus rate of sows. Compared with the CON group, FeSO4 and iron sucrose supplementation increased the serum iron content of weaned piglets (P < 0.05). In addition, iron sucrose increased serum transferrin level of weaned piglets (P < 0.05) and the survival rate of piglets (P < 0.05). In general, both iron sucrose and FeSO4 could affect the blood iron status of weaned piglets, while iron sucrose also had a positive effect on the healthy development of newborn and weaned piglets, and was more effective than FeSO4 in improving the performance of sows and piglets.

Sows need more iron to meet the requirements for their and offspring's growth during pregnancy and lactation. Exogenous iron supplementation may improve the reproductive performance of sows and the growth performance of piglets, but different sources of iron have different effects. This study facilitates the understanding of the effects of iron sucrose and ferrous sulfate on the reproductive performance of sows and the growth performance of piglets.

KLF4 down-regulation underlies placental angiogenesis impairment induced by maternal glucose intolerance in late pregnancy.

Maternal glucose intolerance in late pregnancy can easily impair pregnancy outcomes and placental development. The impairment of placental angiogenesis is closely related to the occurrence of glucose intolerance during pregnancy, but the mechanism remains largely unknown. In this study, the pregnant mouse model of maternal high-fat diet and endothelial injury model of porcine vascular endothelial cells (PVECs) was used to investigate the effect of glucose intolerance on pregnancy outcomes and placental development. Feeding pregnant mice, a high-fat diet was shown to induce glucose intolerance in late pregnancy, and significantly increase the incidence of resorbed fetuses. Moreover, a decrease was observed in the proportion of blood sinusoids area and the expression level of CD31 in placenta, indicating that placental vascular development was impaired by high-fat diet. Considering that hyperglycemia is an important symptom of glucose intolerance, we exposed PVECs to high glucose (50 mM), which verified the negative effects of high glucose on endothelial function. Bioinformatics analysis further emphasized that high glucose exposure could significantly affect the angiogenesis-related functions of PVECs and predicted that Krüppel-like factor 4 (KLF4) may be a key mediator of these functional changes. The subsequent regulation of KLF4 expression confirmed that the inhibition of KLF4 expression was an important reason why high glucose impaired the endothelial function and angiogenesis of PVECs. These results indicate that high-fat diet can aggravate maternal glucose intolerance and damage pregnancy outcome and placental angiogenesis, and that regulating the expression of KLF4 may be a potential therapeutic strategy for maintaining normal placental angiogenesis.

Effects of dietary supplementation of different levels of gamma-aminobutyric acid on reproductive performance, glucose intolerance, and placental development of gilts.

This study aimed to investigate the effects of dietary gamma-aminobutyric acid (GABA) supplementation on reproductive performance, glucose intolerance, and placental development of gilts during mid-late gestation. Based on the principle of backfat thickness consistency, 124 gilts at 65 d of gestation were assigned to three dietary groups: CON (basic diet, n = 41), LGABA (basic diet supplemented with 0.03% GABA, n = 42), and HGABA (basic diet supplemented with 0.06% GABA, n = 41). The litter performance, glucose tolerance, placental angiogenesis, and nutrients transporters were assessed. The LGABA group improved piglet vitality and placental efficiency and decreased area under the curve of glucose tolerance test compared to the CON group (P < 0.05). Meanwhile, the LGABA group enhanced placental vessel density, platelet endothelial cell adhesion molecule-1 levels and gene expression of fibroblast growth factor 18 (P < 0.05). Furthermore, LGABA showed an uptrend in glucose transporter type 1 mRNA level (P = 0.09). Taken together, this study revealed that the dietary supplementation of 0.03% GABA can improve piglet vitality, glucose intolerance, and placental development of gilts.

Glucose homeostasis and placental development are two key factors influencing reproductive performance of sows. Some studies have reported that gamma-aminobutyric acid (GABA) can improve glucose intolerance and cerebral angiogenesis in mice. Therefore, we hypothesized that GABA can improve reproductive performance, glucose intolerance, and placental development of gilts during mid-late gestation. In this study, gilts were randomly assigned into three groups: CON (basal diet), LGABA (basal diet supplemented with 0.03% GABA), and HGABA (basal diet supplemented with 0.06% GABA). Results showed that the LGABA group significantly improved the piglet viability, glucose intolerance, and placental development compared with the CON group. Therefore, GABA has a good prospect as a feed additive for gilts.

Konjac flour-mediated gut microbiota alleviates insulin resistance and improves placental angiogenesis of obese sows.

Our previous study revealed that dietary konjac flour (KF) could remodel gut microbiota and improve reproductive performance of sows, but its underlying mechanisms remain unclear. This experiment aimed to investigate how dietary KF improves reproductive performance of obese sows. Here, 60 sows were assigned into three groups according to their backfat thickness: normal backfat sows fed with control diet (CON-N), high backfat sows fed with control diet (CON-H) and high backfat sows fed with KF inclusion diet (KF-H). The characteristics of sows and piglets were recorded. Next, fecal microbiota transplantation (FMT) was performed on female mice, followed by recording the characteristics of female mice. The results showed that compared with CON-H group, KF-H group showed downtrend in stillbirth rate (P = 0.07), an increase in placental efficiency (P < 0.01) and average piglet weight (P < 0.01); coupled with a decrease in the values of homeostasis model assessment-insulin resistance (P < 0.01); as well as an increase in placental vascular density and protein expression of angiogenesis markers (P < 0.01). As expected, sows fed KF diets had improved abundance and diversity of gut microbiota. More importantly, compared with CON-H(FMT) group, KF-H(FMT) group showed improvement in reproductive performance and insulin sensitivity (P < 0.05), as well as an increase in placental labyrinth zone and protein expression of angiogenesis markers (P < 0.05). Furthermore, we found a content increase (P < 0.05) of SCFAs in both KF-H group sow and KF-H (FMT) group mice. Overall, KF supplementation could alleviate insulin resistance, promote placental angiogenesis, and ultimately improve the reproductive performance of sows via gut microbiota remodeling.

Lachnospiraceae-derived butyrate mediates protection of high fermentable fiber against placental inflammation in gestational diabetes mellitus.

Inflammation-associated insulin resistance is a key trigger of gestational diabetes mellitus (GDM), but the underlying mechanisms and effective interventions remain unclear. Here, we report the association of placental inflammation (tumor necrosis factor-α) and abnormal maternal glucose metabolism in patients with GDM, and a high fermentable dietary fiber (HFDF; konjac) could reduce GDM development through gut flora-short-chain fatty acid-placental inflammation axis in GDM mouse model. Mechanistically, HFDF increases abundances of Lachnospiraceae and butyrate, reduces placental-derived inflammation by enhancing gut barrier and inhibiting the transfer of bacterial-derived lipopolysaccharide, and ultimately resists high-fat diet-induced insulin resistance. Lachnospiraceae and butyrate have similar anti-GDM and anti-placental inflammation effects, and they can ameliorate placental function and pregnancy outcome effects probably by dampening placental immune dysfunction. These findings demonstrate the involvement of important placental inflammation-related mechanisms in the progression of GDM and the great potential of HFDFs to reduce susceptibility to GDM through gut-flora-placenta axis.

Retinoic Acid-PPARα Mediates ß-Carotene Resistance to Placental Dysfunction Induced by Deoxynivalenol.

Deoxynivalenol (DON), one of the most polluted mycotoxins in the environment and food, has been proven to have strong embryonic and reproductive toxicities. However, the effects of DON on placental impairment and effective interventions are still unclear. This study investigated the effect of ß-carotene on placental functional impairment and its underlying molecular mechanism under DON exposure. Adverse pregnancy outcomes were caused by intraperitoneal injection of DON from 13.5 to 15.5 days of gestation in mice, resulting in higher enrichment of DON in placenta than in other tissue samples. Interestingly, 0.1% ß-carotene dietary supplementation could significantly alleviate DON-induced pregnancy outcomes. Additionally, in vivo and in vitro placental barrier models demonstrated the association of DON-induced placental function impairment with placental permeability barrier disruption, angiogenesis impairment, and oxidative stress induction. Moreover, ß-carotene regulated DON-induced placental toxicity by activating the expressions of claudin 1, zonula occludens-1, and vascular endothelial growth factor-A through retinoic acid-peroxisome proliferator-activated receptor α signaling.

Dietary adenosine supplementation improves placental angiogenesis in IUGR piglets by up-regulating adenosine A2a receptor.

Abnormal placental angiogenesis is associated with the occurrence of intrauterine growth restriction (IUGR) in piglets, and effective treatment strategies against this occurrence remain to be explored. Adenosine has been reported to play an important role in angiogenesis, but its role in placental angiogenesis is still unknown. Here, we investigated the effect of dietary adenosine supplementation on IUGR occurrence in piglets by analyzing the role of adenosine in placental angiogenesis for Normal and IUGR piglets. Specifically, 88 sows were allotted to 2 treatments (n = 44) and fed a basal diet supplemented with 0% or 0.1% of adenosine from day 65 of gestation until farrowing, followed by collecting the placental samples of Normal and IUGR piglets, and recording their characteristics. The results showed that adenosine supplementation increased the mean birth weight of piglets (P < 0.05) and placental efficiency (P < 0.05), while decreasing the IUGR piglet rate (P < 0.05). Expectedly, the placenta for IUGR neonates showed a down-regulated vascular density (P < 0.05) and angiogenesis as evidenced by the expression level of vascular cell adhesion molecule-1 (VCAM1) (P < 0.05). Notably, dietary adenosine supplementation promoted angiogenesis (P < 0.05) both in the Normal and IUGR placenta. More importantly, the expression level of adenosine A2a receptor (ADORA2A) was lower (P < 0.05) in the IUGR placenta than in Normal placenta, whereas adenosine treatment could significantly increase ADORA2A expression, and also had an interaction effect between factors IUGR and Ado. Collectively, placentae for IUGR piglets showed impaired angiogenesis and down-regulated expression level of ADORA2A, while dietary adenosine supplementation could activate ADORA2A expression, improve the placental angiogenesis, and ultimately decrease the occurrence of IUGR in piglets.

Cysteamine and N-Acetyl-cysteine Alleviate Placental Oxidative Stress and Barrier Function Damage Induced by Deoxynivalenol.

Sows are highly sensitive to deoxynivalenol (DON) and susceptible to reproductive toxicity caused by oxidative stress, but the potential mechanisms and effective interventions remain unclear. Here, we investigated the role of two antioxidants (cysteamine and N-acetyl-cysteine) in regulating the reproductive performance, redox status, and placental barrier function of sows and their potential mechanisms under DON exposure. Maternal dietary supply of antioxidants from day 85 of gestation to parturition reduced the incidence of stillbirths and low-birth-weight piglets under DON exposure. Moreover, the alleviation of DON-induced reproductive toxicity by dietary antioxidants was associated with the alleviation of placental oxidative stress, the enhancement of the placental barrier, and the vascular function of sows. Furthermore, in vivo and in vitro vascularized placental barrier modeling further demonstrated that antioxidants could reverse both DON transport across the placenta and DON-induced increase of placental barrier permeability. The molecular mechanism of antioxidant resistance to DON toxicity may be related to the signal transducer and activator of the transcription-3-occludin/zonula occludens-1 signaling pathway. Collectively, these results demonstrate the potential of antioxidants to protect the mother from DON-induced reproductive toxicity by alleviating placental oxidative stress and enhancing the placental barrier.

Adenosine-ADORA2A Promotes Ang-Induced Angiogenesis in Intrauterine Growth Restriction Placenta via the Stat3/Akt Pathway.

BACKGROUND: Abnormal placental angiogenesis is an important cause of fetal intrauterine growth restriction (IUGR), but its underlying mechanisms and therapies remain unclear. Adenosine and its mediated signaling has been reported to be associated with the development of angiogenesis. However, whether the adenosine-related signaling plays a role in modulating angiogenesis in placenta and the IUGR pregnancy outcomes remains unclear. METHODS: The angiogenesis and adenosine signaling expressions in normal and IUGR placentas were detected in different species. And the role of adenosine in regulating IUGR pregnancy outcomes was evaluated using diet-induced IUGR mouse model. Molecular mechanisms underlying adenosine-induced angiogenesis were investigated by in vitro angiogenesis assays and in vivo Matrigel plug assays. RESULTS: Here, we demonstrated poor angiogenesis and low adenosine concentration and downregulated expression of its receptor A2a (ADORA2A [adenosine A2a receptor]) in IUGR placenta. Additionally, the beneficial effects of adenosine in improving IUGR pregnancy outcomes were revealed in a diet-induced IUGR mouse model. Moreover, adenosine was found to effectively improve adenosine signaling and angiogenesis in IUGR mice placenta. Mechanistically, by using angiogenesis assays in vitro and in vivo, adenosine was shown to activate ADORA2A to promote the phosphorylation of Stat3 (signal transducer and activator of transcription 3) and Akt (protein kinase B), resulting in increased Ang (angiogenin)-dependent angiogenesis. CONCLUSIONS: Collectively, this study uncovers an unexpected mechanism of promoting placental angiogenesis by adenosine-ADORA2A signaling and advances the translation of this signaling as a prognostic indicator and therapeutic target in IUGR treatment.

Effects of dietary adenosine and adenosine 5'-monophosphate supplementation on carcass characteristics, meat quality, and lipid metabolism in adipose tissues of finishing pigs.

This study investigated the effects of adenosine (ADO) and adenosine 5'-monophosphate (AMP) supplementation on the growth performance, carcass characteristics, meat quality, and lipid metabolism in adipose tissues of finishing pigs. The pigs were allocated to three treatment groups: the control diet, 0.2%ADO diet, or 0.2%AMP diet. Compared with CON group (CON), both ADO and AMP groups increased in carcass straight length (P < 0.05) and decreased in drip loss (P < 0.05), while AMP group tended to increase in redness value (P = 0.05) and decreased in free amino acid content in longissimus thoracis (LT) muscle (P < 0.05). Additionally, ADO or AMP supplementation increased the ADO or AMP content in serum, adipose tissue, and LT muscle (P < 0.05), as well as the protein level of adenosine 2A receptor (A2a) in adipose tissue (P < 0.05). Moreover, both ADO and AMP groups showed an increase in the expression of lipolysis genes (ATGL and HSL) in adipose tissue (P < 0.05). Overall, AMP supplementation could improve meat quality, and ADO and AMP supplementation regulate the lipid metabolism of finishing pigs.

Dietary fiber supplementation during the last 50 days of gestation improves the farrowing performance of gilts by modulating insulin sensitivity, gut microbiota, and placental function.

Our previous study found dietary konjac flour (KF) supplementation could improve insulin sensitivity and reproductive performance of sows, but its high price limits its application in actual production. This study aimed to investigate the effects of supplementation of a cheaper combined dietary fiber (CDF, using bamboo shoots fiber and alginate fiber to partially replace KF) from the last 50 days of gestation to parturition on farrowing performance, insulin sensitivity, gut microbiota, and placental function of gilts. Specifically, a total of 135 pregnant gilts with a similar farrowing time were blocked by backfat thickness and body weight on day 65 of gestation (G65d) and assigned to 1 of the 3 dietary treatment groups (n = 45 per group): basal diet (CON), basal diet supplemented with 2% KF or 2% CDF (CDF containing 15% KF, 60% bamboo shoots fiber, and 25% alginate fiber), respectively. The litter performance, insulin sensitivity and glucose tolerance parameters, placental vessel density, and short-chain fatty acids (SCFAs) levels in feces were assessed. The gut microbiota population in gilts during gestation was also assessed by 16S rDNA gene sequencing. Compared with CON, both KF and CDF treatments not only increased the piglet birth weight (P < 0.05) and piglet vitality (P < 0.01) but also decreased the proportion of piglets with birth weight ≤ 1.2 kg (P < 0.01) and increased the proportion of piglets with birth weight ≥ 1.5 kg (P < 0.01). In addition, KF or CDF supplementation reduced fasting blood insulin level (P < 0.05), homeostasis model assessment-insulin resistance (P < 0.05), serum hemoglobin A1c (P < 0.05), and the level of advanced glycation end products (P < 0.05) at G110d, and increased the placental vascular density (P < 0.05) at farrowing. Meanwhile, KF or CDF supplementation increased microbial diversity (P < 0.05) and SCFAs levels (P < 0.05) in feces at G110d. Notably, the production cost per live-born piglet was lower in CDF group (¥ 36.1) than KF group (¥ 41.3). Overall, KF or CDF supplementation from G65d to farrowing could improve the farrowing performance of gilts possibly by improving insulin sensitivity, regulating gut microbiota and metabolites, and increasing placental vascular density, with higher economic benefits and a similar effect for CDF vs. KF, suggesting the potential of CDF as a cheaper alternative to KF in actual production.

Dietary konjac flour (KF) supplementation could improve insulin sensitivity and reproductive performance of sows, but its high price limits its application in actual production. This study investigated the impact of 2% konjac flour (KF) and 2% combined dietary fiber (CDF, containing 15% KF, 60% bamboo shoots fiber, and 25% alginate fiber) supplementation from the last 50 days of gestation to farrowing on farrowing performance, placental function, insulin sensitivity, and gut microbiota of gilts. Results indicated that KF or CDF supplementation during this time could improve the farrowing performance of gilts possibly by improving insulin sensitivity and gut microbiota, and increasing placental vascular density. Meanwhile, CDF could lower the production cost per live-born piglet and have a similar effect to KF, thus a cheaper alternative to KF in actual production. This study facilitates understanding the beneficial effects of KF and non-conventional dietary fiber sources on the reproductive performance of gilts.

Dietary fibers with low hydration properties exacerbate diarrhea and impair intestinal health and nutrient digestibility in weaned piglets.

BACKGROUND: This study aimed to investigate the hydration properties of different-source fibrous materials by comparing their water-binding capacity (WBC), water swelling capacity (WSC), viscosity, and in vivo effects of selected samples on growth performance, nutrient digestibility, diarrhea, and intestinal health in weaned piglets. METHODS: A total of 13 commercially available fibrous materials were first compared in chemical composition and in vitro hydration property. Subsequently, 40 weaned piglets were randomized to five experimental dietary groups (8 piglets per group): control diet (a basal diet without dietary fiber, CON), basal diet supplemented with 5% microcrystalline cellulose (MCC), 5% wheat bran (WB), 5% Moringa oleifera leaf powder (MOLP), or 5% sugar beet pulp (SBP), followed by analyzing their growth performance and diarrhea rate in a 28-d experiment. After the feeding experiment, anaesthetized piglets were killed, and their intestinal and colon content or plasma samples were analyzed in nutrient digestibility, intestinal morphology, intestinal barrier, short-chain fatty acids (SCFAs), and bacterial population. RESULTS: In vitro studies showed low hydration properties for WB and MCC, while medium hydration properties for MOLP and SBP. In vivo studies indicated that compared with medium hydration property groups, low hydration property groups showed (1) exacerbated diarrhea, impaired intestinal health, and reduced apparent fecal digestibility of dry matter, gross energy, acid detergent fiber, and neutral detergent fiber; (2) decreased SCFAs concentration and relative levels of Lactobacillus and Bifidobacterium, but increased levels of Escherichia coli and Brachyspira hyodysenteriae in colon contents. Additionally, SBP showed optimal performance in reducing diarrhea and increasing SCFAs production. Correlation analysis revealed a positive correlation of fiber hydration properties with in vitro SCFAs production, and diarrhea index and nutrient digestibility were negatively and positively correlated with SCFAs levels in the colon contents of weaned piglets, respectively. CONCLUSIONS: Different-source dietary fibers varied in their hydration properties and impacts on diarrhea, microbial composition and SCFAs production in weaned piglets. WB and MCC could exacerbate diarrhea and impair nutrient digestibility, probably because their low hydration properties were detrimental to gut microbial homeostasis and fermentation. Our findings provide new ideas for rational use of fiber resources in weaned piglets.

Effects of dietary supplementation of gestating sows with adenosine 5'-monophosphate or adenosine on placental angiogenesis and vitality of their offspring.

Our previous study found that dietary nucleotide supplementation, including adenosine 5'-monophosphate (AMP), could increase AMP content in sow milk and promote piglet growth, but its effects on placental efficiency and piglet vitality remain unknown. This experiment aimed to investigate the effects of dietary AMP or its metabolite adenosine (ADO) supplementation on sow reproductive performance and placental angiogenesis. A total of 135 sows with a similar farrowing time were blocked by backfat and body weight (BW) at day 65 of gestation and assigned to one of three dietary treatment groups (n = 45 per treatment): basal diet, basal diet supplemented with 0.1% AMP or 0.1% ADO, respectively. Placental analysis and the characteristics of sows and piglets unveiled that compared with control (CON) group, AMP or ADO supplementation could improve sow placental efficiency (P < 0.05) and newborn piglet vitality (P < 0.05), increase piglet birth weight (P < 0.05), and reduce stillbirth rate (P < 0.05). More importantly, AMP or ADO supplementation could increase the contents of AMP, ADO, and their metabolites in placentae (P < 0.05). Meanwhile, AMP or ADO supplementation could also increase placental vascular density (P < 0.05) and the expression of vascular endothelial growth factor A (P < 0.05), as well as promote the migration and tube formation of porcine iliac artery endothelial cells (P < 0.05). Overall, maternal dietary AMP or ADO supplementation could increase their contents in the placenta, thereby improving placental angiogenesis and neonatal piglet vitality.

Placental angiogenesis regulates piglet growth and development. Adenosine 5ʹ-monophosphate (AMP), a breakdown product of adenosine triphosphate, can be further converted to adenosine with various biological activities. However, little is known about whether AMP supplementation favors piglet growth and development as well as placental angiogenesis. This study facilitates the understanding of the promoting effects of AMP supplementation on placental angiogenesis and farrowing performance.

Dietary adenosine 5'-monophosphate supplementation increases food intake and remodels energy expenditure in mice.

Background: Dietary nucleotides [inclusion adenosine 5'-monophosphate (AMP)] supplementation was shown to promote the feed intake of sows and increase the AMP content in their milk in our previous work, but whether AMP shapes the energy expenditure and lipid metabolism in mammals remains unknown. Here, we aimed to explore the effects and the related mechanism of dietary AMP supplementation on food intake, body composition, energy expenditure, and lipid metabolism in male mice. Methods: 4-week-old C57BL/6 mice (After a 1-wk adaptation) were fed with basal diet and basal diet supplemented with 0.1% AMP, respectively. Animal food intake and body weight were monitored and after 4 weeks all animals were sacrificed to measure the body composition, energy expenditure and lipid metabolism changes. Results: Compared with the control, the 0.1% AMP fed mice showed higher food intake while lower adipose weight. Intriguingly, dietary AMP supplementation was found to stimulate brown adipose tissue thermogenesis as evidenced by the increase in the uncoupling protein-1 level and the core temperature. Moreover, AMP supplementation was shown to promote white adipose tissue lipolysis as indicated by smaller lipid droplet size in mice. These results demonstrate that dietary AMP supplementation could enhance oxygen consumption and energy expenditure. Conclusions: This study highlights the physiological importance of AMP supplementation in mediating food intake and energy expenditure and suggests its potential as an adjuvant therapy in preventing energy metabolic disorders (mainly obesity and diabetes).

UPLC-Orbitrap-MS/MS Combined With Biochemical Analysis to Determine the Growth and Development of Mothers and Fetuses in Different Gestation Periods on Tibetan Sow Model.

Pregnancy is a complex and dynamic process, the physiological and metabolite changes of the mother are affected by different pregnancy stages, but little information is available about their changes and potential mechanisms during pregnancy, especially in blood and amniotic fluid. Here, the maternal metabolism rules at different pregnancy stages were investigated by using a Tibetan sow model to analyze the physiological hormones and nutrient metabolism characteristics of maternal serum and amniotic fluid as well as their correlations with each other. Our results showed that amniotic fluid had a decrease (P < 0.05) in the concentrations of glucose, insulin and hepatocyte growth factor as pregnancy progressed, while maternal serum exhibited the highest concentrations of glucose and insulin at 75 days of gestation (P < 0.05), and a significant positive correlation (P < 0.05) between insulin and citric acid. Additionally, T4 and cortisol had the highest levels during late gestation (P < 0.05). Furthermore, metabolomics analysis revealed significant enrichment in the citrate cycle pathway and the phenylalanine/tyrosine/tryptophan biosynthesis pathway (P < 0.05) with the progress of gestation. This study clarified the adaptive changes of glucose, insulin and citric acid in Tibetan sows during pregnancy as well as the influence of aromatic amino acids, hepatocyte growth factor, cortisol and other physiological indicators on fetal growth and development, providing new clues for the normal development of the mother and the fetus, which may become a promising target for improving the well-being of pregnancy.

A review of the amino acid metabolism in placental function response to fetal loss and low birth weight in pigs.

The fertility of sows mainly depends on the embryo losses during gestation and the survival rate of the post-farrowing piglets. The selection of highly-prolific sows has been mainly focused on the selection of genotypes with high ovulatory quota. However, in the early- and post-implantation stages, the rate of embryo losses was increased with the increase of zygotes. Among the various factors, placental growth and development is the vital determinant for fetal survival, growth, and development. Despite the potential survival of fetuses with deficient placental development, their life-conditions and growth can be damaged by a process termed intrauterine growth retardation (IUGR). The newborn piglets affected by IUGR are prone to increased morbidity and mortality rates; meanwhile, the growth, health and welfare of the surviving piglets will remain hampered by these conditions, with a tendency to exacerbate with age. Functional amino acids such as glycine, proline, and arginine continue to increase with the development of placenta, which are not only essential to placental growth (including vascular growth) and development, but can also be used as substrates for the production of glutathione, polyamines and nitric oxide to benefit placental function in many ways. However, the exact regulation mechanism of these amino acids in placental function has not yet been clarified. In this review, we provide evidence from literature and our own work for the role and mechanism of dietary functional amino acids during pregnancy in regulating the placental functional response to fetal loss and birth weight of piglets. This review will provide novel insights into the response of nutritionally nonessential amino acids (glycine and proline) to placental development as well as feasible strategies to enhance the fertility of sows.

Arginine Promotes the Expression of Aquaporin-3 and Water Transport in Porcine Trophectoderm Cells Through NO- and cAMP-Dependent Mechanisms.

BACKGROUND: Dietary supplementation with L-arginine (Arg) has been shown to increase the volume of fetal fluids in gestating swine. Aquaporins (AQPs), known as water channel proteins, are essential for embryonic growth and development. It was not known if Arg mediates water transport through AQPs in porcine conceptus trophectoderm (pTr2) cells. METHODS: pTr2 cells derived from pregnant gilts on day 12 of gestation were cultured in customized Arg-free Dulbecco's modified Eagle's Ham medium (DMEM) supplemented with either 0.00, 0.25, or 0.50 mM Arg. RESULTS: Arg treatment increased water transport and the expression of AQP3, which was abundantly expressed in pTr2 cells at both the mRNA and protein levels. Arg also increased the expression of iNOS and the synthesis of nitric oxide (NO) in pTr2 cells. The presence of Nω-nitro-L-arginine methyl ester hydrochloride (L-NAME; an inhibitor of NO synthase) significantly attenuated the Arg-induced expression of AQP3. Furthermore, 0.50 mM Arg increased the concentrations of cAMP and the abundances of phosphorylated cAMP-dependent protein kinase A (PKA), phosphorylated PKA α/ß/γ, and phosphorylated CREB. These effects of Arg were mimicked by Forskolin (a cell-permeable activator of adenylyl cyclase), but inhibited by H-89 (an inhibitor of cAMP-dependent protein kinase). CONCLUSIONS: The results of this study demonstrate that Arg regulates AQP3 expression and promotes water transport in pTr2 cells through NO- and cAMP-dependent signaling pathways.

Starch supplementation improves the reproductive performance of sows in different glucose tolerance status.

This study was to evaluate the effects of glucose tolerance status, maternal starch supplementation and soybean substitution in diets on the performance of dams and their offspring. Eighty-eight pregnant sows (Landrace × Large White) were selected from an initial total of 120 sows, based on blood glucose test values, and assigned to 4 experimental treatments in a 2 × 2 factorial design. The factors were glucose tolerance status (glucose intolerant [GIT] vs. normal glucose tolerant [NGT]) or dietary treatments (corn starch diet [CS] vs. soybean substitution diet [SS]). A higher area under the curve (AUC) for post-meal glucose was observed (P < 0.05) in the GIT group than in the NGT group on d 109 of gestation. The CS group had a lower value of homeostasis model assessment-insulin resistance than the SS group (P < 0.05) on d 109 of gestation. Corn starch supplementation for sows decreased the stillbirth rate (P < 0.05), regardless of the sows' glucose tolerance status. The villus height of the jejunum and the villus height to crypt depth ratio of the ileum were greater in normal birth weight piglets from the CS group than from the SS group (P < 0.01), and so was the activity of sucrase in the jejunum and ileum (P < 0.01). Compared with the SS group, the CS group showed a reduction in pre-weaning mortality rate, an increase in the number of high-birth-weight piglets, and a decrease in the number of low-birth-weight piglets (P < 0.05) under GIT status. In conclusion, sows fed CS decreased stillbirth rate and improved insulin resistance, as well as improving the intestinal morphology and digestive enzyme activities of their progeny, regardless of glucose tolerance status. Additionally, the CS group improved birth weight distribution and decreased pre-weaning mortality rate of piglets under GIT status.