作者机构：
[Liu, Yulan; Wang, Dan; Li, Shunkang; Wu, Nianbang; He, Wensheng; Kuang, Yanling; Zhu, Huiling] Hubei Key Laboratory of Animal Nutrition and Feed Science, Wuhan Polytechnic University, Wuhan, China;[Gao, Qingyu; Cong, Xin] Enshi Se-Run Material Engineering Technology Co., Ltd., Enshi, China;[Liu, Liping] Beijng Center for Disease Prevention and Control, Beijing, China;[Cheng, Shuiyuan] National R&D Center for Se-rich Agricultural Products Processing, School of Modern Industry for Selenium Science and Engineering, Wuhan Polytechnic University, Wuhan, China
通讯机构：
[Xin Cong] E;[Dan Wang] H;Enshi Se-Run Material Engineering Technology Co., Ltd., Enshi, China<&wdkj&>Hubei Key Laboratory of Animal Nutrition and Feed Science, Wuhan Polytechnic University, Wuhan, China
摘要：
This study aimed to investigate the impact of Cardamine violifolia on muscle protein degradation, the inflammatory response and antioxidant function in weaned piglets following LPS challenge. Twenty-four weaned piglets were used in a 2 × 2 factorial experiment with dietary treatment (sodium selenite or Cardamine violifolia) and LPS challenge. After 28 days of feeding, pigs were injected intraperitoneally with 100 μg/kg LPS or saline. Dietary supplementation with Cardamine violifolia mitigated the reduction in insulin and growth hormone levels induced by LPS. It also curbed the LPS-induced elevation of plasma glucagon, urea nitrogen, and creatinine concentrations. Cardamine violifolia reduced muscle damage caused by LPS, as evidenced by increased protein content and protein/DNA ratio and decreased TNF-α and IL-1β mRNA expression. Furthermore, Cardamine violifolia modulated the expression of FOXO1, FOXO4, and MuRF1 in muscle, indicative of the protective effect against muscle protein degradation. Enhanced muscle antioxidant function was observed in the form of increased T-AOC, reduced MDA concentration, and decreased mRNA expression of GPX3, DIO3, TXNRD1, SELENOS, SELENOI, SELENOO, and SEPHS2 in LPS-treated piglets. The findings suggest that Cardamine violifolia supplementation can effectively alleviate muscle protein degradation induced by LPS and enhance the antioxidant capacity in piglets.
摘要：
The proportion of n-6 and n-3 polyunsaturated fatty acid (PUFA) in commercial pig feed is severely unbalanced. This study was conducted to investigate the effects of different n-6/n-3 PUFA ratios on growth performance and lipid metabolism of nursery pigs. A total of 240 nursery pigs (Duroc × Large White × Landrace) were fed diets with different n-6/n-3 PUFA ratios, including 10:1, 5:1, 3:1, and 1.5:1. Pigs fed diet with n-6/n-3 PUFA ratio of 1.5:1 or 3:1 had optimum average daily gain and feed to gain ratio (P < 0.05). The levels of serum lipids including total cholesterol, triglyceride, high density lipoprotein and low density lipoprotein were the lowest in pigs fed diet with n-6/n-3 PUFA ratio of 1.5:1 (P < 0.05). The concentrations of serum insulin, adiponectin and leptin were the highest in pigs fed diet with n-6/n-3 PUFA ratio of 3:1 (P < 0.05).Pigs fed diet with n-6/n-3 PUFA ratio of 3:1 had the highest abundance of genes associated with fatty acid absorption and transportation (FATP4, and PPARγ), synthesis and storage (FAS and GPAT) and degradation (ATGL, HSL, and MAGL) in intestine (P < 0.05). Pigs fed diet with n-6/n-3 PUFA ratio of 1.5:1 had the lowest abundance of genes associated with fatty acid absorption (CD36 and FABP4), synthesis and storage (ACC, FAS, ACLY, PAP, AGPAT, and GPAT) and degradation (CPT1 and HSL) in gastrocnemius muscle (P < 0.05). The mRNA expression of genes associated with fatty acid metabolism (FATP2, FATP5, FABP1, FABP4, LPL, ACS, ACLY, AGPAT, GPAT, CPT1, ATGL, and MAGL) was up-regulated in liver and subcutaneous fat of pigs fed diet with n-6/n-3 PUFA ratios of 1.5:1-5:1 (P < 0.05). In summary, diets with lower n-6/n-3 PUFA ratios improve growth performance, reduce blood lipids, facilitate lipid metabolism in intestine, liver and subcutaneous fat, and inhibit fatty acid absorption, synthesis and storage in gastrocnemius muscle in pigs.
摘要：
Ferroptosis is a newly identified form of regulated cell death (RCD) characterized by iron overload and excessive lipid peroxidation. To date, numerous studies in human and mouse models have shown that ferroptosis is closely related to tissue damage and various diseases. In recent years, ferroptosis has also been found to play an indispensable and multifaceted role in infection and tissue injury in pigs, and nutritional regulation strategies targeting ferroptosis show great potential. In this review, we summarize the research progress of ferroptosis and its role in infection and tissue injury in pigs. Furthermore, we discuss the existing evidence on ferroptosis regulation by nutrients, aiming to provide valuable insights for future investigation into ferroptosis in pigs and offer a novel perspective for the treatment of infection and injury in pigs.
摘要：
In the early stages of development, piglets exhibit immature intestinal morphology and function, rendering them susceptible to a range of internal and external stressors, such as viral and bacterial infection, and mycotoxin exposure, which causes intestinal damage. The intestinal damage is characterized by various types of cell death within intestinal epithelium. The traditional cell death types have been categorized as necrosis, apoptosis, and autophagy. However, recent research has identified several forms of novel regulated cell death (RCD) such as necroptosis, pyroptosis, and ferroptosis. A growing body of evidence has underscored the pivotal role of necroptosis, pyroptosis, and ferroptosis in intestinal damage in pigs. Moreover, intervention strategies have been shown to mitigate these 3 RCDs when pigs are exposed to excessive adverse factors. This review aims to elucidate the role of these emerging RCDs in intestinal damage and summarize current understanding of their regulation by nutrients and bioactive substances in pigs. Our goal was to provide future intervention strategies designed to alleviate intestinal damage in pigs.
In the early stages of development, piglets exhibit immature intestinal morphology and function, rendering them susceptible to a range of internal and external stressors, such as viral and bacterial infection, and mycotoxin exposure, which causes intestinal damage. The intestinal damage is characterized by various types of cell death within intestinal epithelium. The traditional cell death types have been categorized as necrosis, apoptosis, and autophagy. However, recent research has identified several forms of novel regulated cell death (RCD) such as necroptosis, pyroptosis, and ferroptosis. A growing body of evidence has underscored the pivotal role of necroptosis, pyroptosis, and ferroptosis in intestinal damage in pigs. Moreover, intervention strategies have been shown to mitigate these 3 RCDs when pigs are exposed to excessive adverse factors. This review aims to elucidate the role of these emerging RCDs in intestinal damage and summarize current understanding of their regulation by nutrients and bioactive substances in pigs. Our goal was to provide future intervention strategies designed to alleviate intestinal damage in pigs.
摘要：
Aging-related lipid metabolic disorder is related to oxidative stress. Selenium (Se)-enriched Cardamine violifolia (SEC) is known for its excellent antioxidant function. The objective of this study was to evaluate the effects of SEC on antioxidant capacity and lipid metabolism in the liver of aged laying hens. A total of 450 sixty-five-wk-old Roman laying hens were randomly divided into 5 treatments: a basal diet (without Se supplementation, CON) and basal diets supplemented with 0.3 mg/kg Se from sodium selenite (SS), 0.3 mg/kg Se from Se-enriched yeast (SEY), 0.3 mg/kg Se from SEC (SEC), or 0.3 mg/kg Se from SEC and 0.3 mg/kg Se from SEY (SEC + SEY). The experiment lasted for 8 wk. The results showed that dietary SEC + SEY supplementation decreased (P < 0.05) triglyceride (in the plasma and liver) and total cholesterol levels (in the plasma), and increased (P < 0.05) HDL-C concentration in plasma compared to CON diet. Compared with CON diet, SEC and/or SEY supplementation decreased (P < 0.05) the mRNA expression of hepatic ACC, FAS and HMGCR, and increased (P < 0.05) PPARα, VTG-II, Apo-VLDL II and ApoB expression. Dietary SEC + SEY and SEY supplementation increased (P < 0.05) Se content in egg yolk and breast muscle compared to CON diet. Dietary SEC, SEY or SEC + SEY supplementation increased (P < 0.05) the activity of antioxidant enzymes (GSH-PX, T-AOC and T-SOD) in the plasma and liver and decreased (P < 0.05) MDA content in the plasma compared to CON diet. Dietary Se supplementation promoted (P < 0.05) mRNA expression of Nrf2 in the liver. In contrast, dietary SEY and SEC supplementation resulted in a decrease (P < 0.05) of hepatic Keap1 mRNA expression compared to CON diet. Dietary SEC + SEY and/or SEC supplementation increased (P < 0.05) mRNA expression of Selenof, GPX1 and GPX4 in the liver compared with CON diet. In conclusion, dietary SEC (0.3 mg/kg Se) or SEC (0.3 mg/kg Se) + SEY (0.3 mg/kg Se) improved the antioxidant capacity and the lipid metabolism in the liver of aged laying hens, which might be associated with regulating Nrf2/Keap1 signaling pathway.
Aging-related lipid metabolic disorder is related to oxidative stress. Selenium (Se)-enriched Cardamine violifolia (SEC) is known for its excellent antioxidant function. The objective of this study was to evaluate the effects of SEC on antioxidant capacity and lipid metabolism in the liver of aged laying hens. A total of 450 sixty-five-wk-old Roman laying hens were randomly divided into 5 treatments: a basal diet (without Se supplementation, CON) and basal diets supplemented with 0.3 mg/kg Se from sodium selenite (SS), 0.3 mg/kg Se from Se-enriched yeast (SEY), 0.3 mg/kg Se from SEC (SEC), or 0.3 mg/kg Se from SEC and 0.3 mg/kg Se from SEY (SEC + SEY). The experiment lasted for 8 wk. The results showed that dietary SEC + SEY supplementation decreased (P < 0.05) triglyceride (in the plasma and liver) and total cholesterol levels (in the plasma), and increased (P < 0.05) HDL-C concentration in plasma compared to CON diet. Compared with CON diet, SEC and/or SEY supplementation decreased (P < 0.05) the mRNA expression of hepatic ACC, FAS and HMGCR, and increased (P < 0.05) PPARα, VTG-II, Apo-VLDL II and ApoB expression. Dietary SEC + SEY and SEY supplementation increased (P < 0.05) Se content in egg yolk and breast muscle compared to CON diet. Dietary SEC, SEY or SEC + SEY supplementation increased (P < 0.05) the activity of antioxidant enzymes (GSH-PX, T-AOC and T-SOD) in the plasma and liver and decreased (P < 0.05) MDA content in the plasma compared to CON diet. Dietary Se supplementation promoted (P < 0.05) mRNA expression of Nrf2 in the liver. In contrast, dietary SEY and SEC supplementation resulted in a decrease (P < 0.05) of hepatic Keap1 mRNA expression compared to CON diet. Dietary SEC + SEY and/or SEC supplementation increased (P < 0.05) mRNA expression of Selenof, GPX1 and GPX4 in the liver compared with CON diet. In conclusion, dietary SEC (0.3 mg/kg Se) or SEC (0.3 mg/kg Se) + SEY (0.3 mg/kg Se) improved the antioxidant capacity and the lipid metabolism in the liver of aged laying hens, which might be associated with regulating Nrf2/Keap1 signaling pathway.
摘要：
Oxidative stress occurs in the process of egg storage. Antioxidants as feed additives can enhance egg quality and extend the shelf life of eggs. Selenium-enriched Cardamine violifolia (SEC) has strongly antioxidant properties. The objective of this study was to assess the effects of dietary supplementation with SEC on egg quality and the yolk antioxidant capacity of eggs stored at 4 °C and 25 °C. Four hundred fifty 65-week-old, Roman hens that were similar in laying rate (90.79 ± 1.69%) and body weight (2.19 ± 0.23 kg) were divided into 5 groups. The birds were fed diets supplemented with 0 mg/kg selenium (Se) (CON), 0.3 mg/kg Se from sodium selenite (SS), 0.3 mg/kg Se from Se-enriched yeast (SEY), 0.3 mg/kg Se for selenium-enriched Cardamine violifolia (SEC) or 0.3 mg/kg Se from Se-enriched Cardamine violifolia and 0.3 mg/kg Se from Se-enriched yeast (SEC + SEY) for 8 weeks. The eggs were collected on the 8th week and were analyzed for egg quality and oxidative stability of yolk during storage at 4 °C or 25 °C for 0, 2, 4, or 6 weeks. Dietary SEC and SEC + SEY supplementation increased the Haugh unit (HU) and albumen foam stability in eggs stored at 4 °C and 25 °C (p < 0.05). SS and SEC supplementation increased the yolk index in eggs stored at 25 °C (p < 0.05). SEC or SEC + SEY slowed down an increase in albumen pH and gel firmness in eggs stored at 4 °C and 25 °C (p < 0.05). Moreover, SEC or SEC + SEY alleviated the increase in malonaldehyde (MDA), and the decrease in total antioxidant capacity (T-AOC) level and total superoxide dismutase (T-SOD) activity in yolks stored at 4 °C and 25 °C (p < 0.05). These results indicate that SEC mitigated egg quality loss and improved the antioxidant capacity of yolks during storage. SEC supplementation would be advantageous to extend the shelf life of eggs.
摘要：
ScopeFerroptosis has been demonstrated to play an important role in various tissue injuries and diseases. Flaxseed oil (FO) has been proven to have benefits for intestinal health. This study aims to explore whether FO relieved lipopolysaccharide (LPS)-induced intestinal injury through modulating ferroptosis signaling pathway.Methods and resultsA total of 120 weaned piglets are fed diets with 3% soybean oil (SO) or 3% FO for 4 weeks. At the end of the trial, 24 piglets selected from two dietary treatment groups are used in a 2 x 2 factorial design with oil treatment (3% SO versus 3% FO) and LPS challenge (saline versus LPS). At 4 h postinjection with LPS, 24 piglets are slaughtered and intestinal samples are collected. FO improves growth performance of pigs. After LPS treatment, FO mitigates intestinal morphological damage and functional damage. Notably, FO reverses the typical ultra-morphology and biochemical indexes of ferroptosis involving glutathione, malondialdehyde, and 4-hydroxynonenal contents. Mechanistically, FO ameliorates the changes on mRNA or protein abundance of key ferroptosis signals including transferrin receptor protein 1 (TFR1), recombinant iron responsive element binding protein 2 (IREB2), FTL, HSPB1, ferritin heavy chain 1 (FTH1), ferroportin 1 (FPN1), SLC7A11, solute carrier family 3 member 2 (SLC3A2), glutathione peroxidase 4 (GPX4), and arachidonate-15-lipoxygenase (ALOX15).ConclusionsFO improves growth performance and mitigates intestinal structural and functional damage, which is involved in regulating ferroptosis signaling pathway. Structural and functional damage occurred in the intestines of piglets after injection of LPS. Mechanistically, LPS induced ferroptosis in intestinal epithelial cells and activated this signaling pathway. However, Flaxseed oil (FO) improved growth performance of pigs. After LPS treatment, FO mitigated intestinal morphological and functional damage. FO ameliorated the changes on mRNA or protein abundance of key ferroptosis signals including TFR1, IREB2, FTL, HSPB1, FTH1, ferroportin 1, SLC7A11, SLC3A2, GPX4, and ALOX15. image
摘要：
The aim of this study was to investigate the role of necroptosis in deoxynivalenol (DON)-induced liver injury and inflammation in weaned piglets. In Exp. 1, 12 weaned piglets were divided into 2 groups including pigs fed basal diet and pigs fed diet contaminated with 4 mg/kg DON for 21 d. In Exp. 2, 12 weaned piglets were divided into 2 groups including control piglets and piglets given a gavage of 2 mg/kg body weight (BW) DON. In Exp. 3, 24 weaned piglets were used in a 2 × 2 factorial design and the main factors including necrostatin-1 (Nec-1) (DMSO or 0.5 mg/kg BW Nec-1) and DON challenge (saline or 2 mg/kg BW DON gavage). On 21 d in Exp. 1, or at 6 h post DON gavage in Exp. 2 and 3, pigs were killed for blood samples and liver tissues. Liver histology, blood biochemical indicators, and liver inflammation and necroptosis signals were tested. Dietary or oral gavage with DON caused liver morphological damage in piglets. Dietary DON led to hepatocyte damage indicated by increased aspartate transaminase (AST) activity and AST/alanine aminotransferase (ALT) ratio, and DON gavage also caused hepatocyte damage and cholestasis indicated by increased AST and alkaline phosphatase (AKP) activities. Dietary DON caused liver necroptosis indicated by increased protein abundance of total receptor interacting protein kinase 3 (t-RIP3) and total mixed lineage kinase domain-like protein (t-MLKL). Moreover, DON gavage increased mRNA expression of interleukin (IL)-6 and IL-1β in liver. DON gavage also induced liver necroptosis demonstrated by increased protein abundance of t-RIP3, phosphorylated-RIP3 (p-RIP3), t-MLKL and p-MLKL. However, pretreatment with Nec-1, a specific inhibitor of necroptosis, inhibited liver necroptosis indicated by decreased protein expression of t-RIP3, p-RIP3, t-MLKL and p-MLKL. Nec-1 pretreatment reduced liver morphological damage after DON gavage. Pretreatment with Nec-1 also attenuated liver damage induced by DON indicated by decreased activities of AST and AKP. Furthermore, Nec-1 pretreatment inhibited liver mRNA expression of IL-6 and IL-1β after DON challenge. Our data demonstrate for the first time that necroptosis contributes to DON-induced liver injury and inflammation in piglets.
摘要：
Deoxynivalenol (DON) is a secondary metabolite produced by fungi, which causes serious health issues worldwide due to its widespread presence in human and animal diets. Necroptosis is a newly proposed cell death mode and has been proposed as a potential mechanism of intestinal disease. This study aimed to investigate the role of necroptosis in intestinal damage caused by DON exposure. Piglets were fed diets with or without 4mg/kg DON for 3 weeks or given a gavage of 2mg/kg BW DON or sterile saline to investigate the effects of chronic or acute DON exposure on the gut, respectively. IPEC-1 cells were challenged with different concentrations of DON to investigate the effect of DON exposure on the intestinal epithelial cells (IECs) in vitro. Subsequently, the inhibitors of necroptosis were used to treat cells or piglets prior to DON challenge. Chronic and acute DON exposure both caused morphological damage, reduction of disaccharidase activity, decrease of tight junction protein expression, inflammation of the small intestine, and necroptosis of intestinal epithelial cells in piglets. Necroptosis was also detected when IPEC-1 cell damage was induced by DON in vitro. The suppression of necroptosis in IPEC-1 cells by inhibitors (necrostatin-1 (Nec-1), GSK'872, or GW806742X) alleviated cell death, the decrease of tight junction protein expression, oxidative stress, and the inflammatory response induced by DON. Furthermore, pre-treatment with Nec-1 in piglets was also observed to protect the intestine against DON-induced enterotoxicity. Additionally, the expression of histone methyltransferase SETDB1 was abnormally downregulated upon chronic and acute DON exposure in piglets, and necroptosis was activated in IPEC-1 cells due to knockout of SETDB1. Collectively, these results demonstrate that necroptosis of IECs is a mechanism of DON-induced enterotoxicity and SETDB1 mediates necroptosis upon DON exposure in IECs, suggesting the potential for targeted inhibition of necroptosis to alleviate mycotoxin-induced enterotoxicity and intestinal disease.
摘要：
Selenium-enriched Cardamine violifolia (SEC), a cruciferous plant, exerts excellent antioxidant and anti-inflammatory capacity, but its effect on hepatic function is unclear. This study investigated the effect and potential mechanism of SEC on hepatic injury induced by lipopolysaccharide (LPS). Twenty-four weaned piglets were randomly allotted to treatment with SEC (0.3 mg/kgSe) and/or LPS (100 μg/kg). After 28 days of the trial, pigs were injected with LPS to induce hepatic injury. These results indicated that SEC supplementation attenuated LPS-induced hepatic morphological injury and reduced aspartate aminotransferase (AST) and alkaline phosphatase (ALP) activities in plasma. SEC also inhibited the expression of pro-inflammatory cytokines such as interleukin 6 (IL-6) and tumor necrosis factor-alpha (TNF-α) after the LPS challenge. In addition, SEC improved hepatic antioxidant capacity via enhancing glutathione peroxidase (GSH-Px) activity and decreasing malondialdehyde (MDA) concentration. Moreover, SEC downregulated the mRNA expression of hepatic myeloid differentiation factor 88 (MyD88) and nucleotide-binding oligomerization domain proteins 1 (NOD1) and its adaptor molecule receptor interacting protein kinase 2 (RIPK2). SEC also alleviated LPS-induced hepatic necroptosis by inhibiting RIPK1, RIPK3, and mixed-lineage kinase domain-like (MLKL) expression. These data suggest that SEC potentially mitigates LPS-induced hepatic injury via inhibiting Toll-like receptor 4 (TLR4)/NOD2 and necroptosis signaling pathways in weaned piglets.
摘要：
The mycotoxin deoxynivalenol (DON) is highly prevalent in cereals as an immune stressor. The hypothalamic-pituitary-adrenal (HPA) axis is activated during periods of stress, and the organism is accompanied by inflammation. Necroptosis is a newly identified type of cell death. However, the relationship between necroptosis and HPA axis activation induced by DON is rarely reported. Our study aimed to explore the role played by necroptosis in HPA activation in a stress of piglet model produced by DON. Our results indicated that both feeding with a contaminated-DON diet (4ppm) and DON injection at 0.8mg/kg BW increased the concentration of plasma corticotropin-releasing hormone (CRH) and adrenocorticotrophic hormone (ACTH) and the mRNA expression of adrenal steroidogenic acute regulatory protein (StAR). Furthermore, the mRNA expression of pro-inflammatory cytokines and factors related to necroptosis in the hypothalamus, pituitary gland, and adrenal gland were increased. As an inhibitor of necroptosis, necrostatin-1 (Nec-1) inhibited necroptosis through decreasing mRNA expression of necroptosis signal factors in the HPA axis. Nec-1 also reduced the mRNA levels of pro-inflammatory cytokines in the HPA axis. Meanwhile, the activation of the HPA axis was inhibited by Nec-1 as shown by the decrease of plasma CRH and ACTH concentrations and the mRNA expressions of hypothalamus CRH and pituitary POMC. These findings indicated that as a result of necroptosis, the HPA axis was activated by DON. In light of these findings, necroptosis could be considered as an intervention target that alleviates HPA axis activation and stress responses.
摘要：
Selenium, as an essential trace element, exerts health effects that are contingent not only on the quantity consumed but also on the specific selenium species present in the dietary. The aim of this study was to investigate the effects of different selenium supplements on the distribution of selenium content, the forms of selenium, and its in vitro bioaccessibility in piglets. Inductively coupled plasma mass spectrometry and high-performance liquid chromatography (HPLC-ICP/MS) were applied to analyze the selenium content and its speciation in tissues and organs of piglets fed with three selenium supplements, sodium selenite (SS), selenium-enriched Cardamine hirsute (CH), and selenium-enriched yeast (SY). The bioaccessibility experiments on the livers of selenium-enriched piglets were conducted by simulating human gastrointestinal digestion. It was found that the kidney has the highest selenium content among the 12 examined organs. The efficacy of different selenium sources in improving the selenium content in piglets ranked in descending order, is as follows: SY, SS, and CH. The predominant form of selenium in the longissimus dorsi muscle is selenomethionine (SeMet), accompanied by smaller quantities of selenocysteine (SeCys) and methyl selenocysteine (MeSeCys). In contrast, the predominant selenium form in the liver is SeCys, along with SeMet and MeSeCys. Piglets fed with Se-enriched yeast exhibited a significant increase in the content and proportion of SeMet in both the longissimus dorsi muscle and liver. Additionally, different selenium species demonstrated varied G and GI bioaccessilities, with SeMet being the highest and SeCys the lowest.
Selenium, as an essential trace element, exerts health effects that are contingent not only on the quantity consumed but also on the specific selenium species present in the dietary. The aim of this study was to investigate the effects of different selenium supplements on the distribution of selenium content, the forms of selenium, and its in vitro bioaccessibility in piglets. Inductively coupled plasma mass spectrometry and high-performance liquid chromatography (HPLC-ICP/MS) were applied to analyze the selenium content and its speciation in tissues and organs of piglets fed with three selenium supplements, sodium selenite (SS), selenium-enriched Cardamine hirsute (CH), and selenium-enriched yeast (SY). The bioaccessibility experiments on the livers of selenium-enriched piglets were conducted by simulating human gastrointestinal digestion. It was found that the kidney has the highest selenium content among the 12 examined organs. The efficacy of different selenium sources in improving the selenium content in piglets ranked in descending order, is as follows: SY, SS, and CH. The predominant form of selenium in the longissimus dorsi muscle is selenomethionine (SeMet), accompanied by smaller quantities of selenocysteine (SeCys) and methyl selenocysteine (MeSeCys). In contrast, the predominant selenium form in the liver is SeCys, along with SeMet and MeSeCys. Piglets fed with Se-enriched yeast exhibited a significant increase in the content and proportion of SeMet in both the longissimus dorsi muscle and liver. Additionally, different selenium species demonstrated varied G and GI bioaccessilities, with SeMet being the highest and SeCys the lowest.
摘要：
Introduction Inflammatory bowel disease (IBD) is often associated with impaired proliferation and differentiation of intestinal stem cells (ISCs). Eicosapentaenoic acid (EPA), which is predominantly found in fish oil, has been recognized for its intestinal health benefits, although the potential mechanisms are not well understood.
Inflammatory bowel disease (IBD) is often associated with impaired proliferation and differentiation of intestinal stem cells (ISCs). Eicosapentaenoic acid (EPA), which is predominantly found in fish oil, has been recognized for its intestinal health benefits, although the potential mechanisms are not well understood.
Objectives This study aimed to investigate the regulatory role and mechanism of EPA in colonic epithelial regeneration, specifically from the perspective of ISCs.
This study aimed to investigate the regulatory role and mechanism of EPA in colonic epithelial regeneration, specifically from the perspective of ISCs.
Methods Wild-type mice whose diet was supplemented with 5% EPA-enriched fish oil were subjected to dextran sulfate sodium (DSS) to induce colitis. We utilized intestinal organoids, ISC-specific lysine-specific demethylase 1 (LSD1) knockout mice, and WNT inhibitor-treated mice to explore how EPA influences ISC proliferation and differentiation. ISC proliferation, differentiation and apoptosis were assessed using tdTomato and propidium iodide tracer testing, histological analyses, and immunofluorescence staining.
Wild-type mice whose diet was supplemented with 5% EPA-enriched fish oil were subjected to dextran sulfate sodium (DSS) to induce colitis. We utilized intestinal organoids, ISC-specific lysine-specific demethylase 1 (LSD1) knockout mice, and WNT inhibitor-treated mice to explore how EPA influences ISC proliferation and differentiation. ISC proliferation, differentiation and apoptosis were assessed using tdTomato and propidium iodide tracer testing, histological analyses, and immunofluorescence staining.
Results EPA treatment significantly mitigated the symptoms of DSS-induced acute colitis, as evidenced by lower body weight loss and decreased disease activity index, histological scores and proinflammatory cytokine levels. Additionally, EPA increased the numbers of proliferative cells, absorptive cells, goblet cells, and enteroendocrine cells, which enhanced the regeneration of intestinal epithelium. Pretreatment with EPA increased ISC proliferation and differentiation, and protected against TNF-α-induced cell death in intestinal organoids. Mechanistically, EPA upregulated G protein-coupled receptor 120 (GPR120) to induce LSD1 expression, which facilitated ISC proliferation and differentiation in organoids. ISC-specific ablation of LSD1 negated the protective effect of EPA on DSS-induced colitis in mice. Moreover, EPA administration activated the WNT signaling pathway downstream of LSD1 in ISCs, while inhibiting WNT signaling abolished the beneficial effects of EPA.
EPA treatment significantly mitigated the symptoms of DSS-induced acute colitis, as evidenced by lower body weight loss and decreased disease activity index, histological scores and proinflammatory cytokine levels. Additionally, EPA increased the numbers of proliferative cells, absorptive cells, goblet cells, and enteroendocrine cells, which enhanced the regeneration of intestinal epithelium. Pretreatment with EPA increased ISC proliferation and differentiation, and protected against TNF-α-induced cell death in intestinal organoids. Mechanistically, EPA upregulated G protein-coupled receptor 120 (GPR120) to induce LSD1 expression, which facilitated ISC proliferation and differentiation in organoids. ISC-specific ablation of LSD1 negated the protective effect of EPA on DSS-induced colitis in mice. Moreover, EPA administration activated the WNT signaling pathway downstream of LSD1 in ISCs, while inhibiting WNT signaling abolished the beneficial effects of EPA.
Conclusions These findings demonstrate that EPA promotes ISC proliferation and differentiation, thereby enhancing colonic epithelial regeneration through the activation of LSD1-WNT signaling. Consequently, dietary supplementation with EPA represents a promising alternative therapeutic strategy for managing IBD.
These findings demonstrate that EPA promotes ISC proliferation and differentiation, thereby enhancing colonic epithelial regeneration through the activation of LSD1-WNT signaling. Consequently, dietary supplementation with EPA represents a promising alternative therapeutic strategy for managing IBD.
作者机构：
Hubei Provincial Center of Technology Innovation for Domestic Animal Breeding, Wuhan 430023, China;Laboratory of Genetic Breeding, School of Animal Science and Nutritional Engineering, Reproduction and Precision Livestock Farming, Wuhan Polytechnic University, Wuhan 430023, China;[Hongyan Ren] Key Laboratory of Animal Embryo Engineering and Molecular Breeding of Hubei Province, Institute of Animal Husbandry and Veterinary, Hubei Academy of Agricultural Sciences, Wuhan 430064, China;These authors contributed equally to this work.;[Zhe Chao] Hainan Key Laboratory for Tropical Animal Breeding and Disease Research, Institute of Animal Science and Veterinary Medicine, Hainan Academy of Agricultural Sciences, Haikou 571100, China
通讯机构：
[Ling Guo] H;Hubei Collaborative Innovation Center for Animal Nutrition and Feed Safety, Wuhan 430023, China<&wdkj&>Hubei Provincial Center of Technology Innovation for Domestic Animal Breeding, Wuhan 430023, China<&wdkj&>Laboratory of Genetic Breeding, School of Animal Science and Nutritional Engineering, Reproduction and Precision Livestock Farming, Wuhan Polytechnic University, Wuhan 430023, China<&wdkj&>Hubei Key Laboratory of Animal Nutrition and Feed Science, Wuhan Polytechnic University, Wuhan 430023, China<&wdkj&>Author to whom correspondence should be addressed.
关键词：
long untranslated RNA;transcriptome;animal experiment;animal model;animal tissue;arthritis;Article;controlled study;differential expression analysis;differential gene expression;glaesserella parasuis;inflammation;KEGG;meningitis;nonhuman;pathogenesis;Pi3K/Akt signaling;piglet;pneumonia;polyserositis;protein expression;protein protein interaction;real time polymerase chain reaction;RNA sequence;TNF signaling;weighted gene co expression network analysis
