Dietary Beta-Hydroxy Beta-Methyl Butyrate Supplementation Alleviates Liver Injury in Lipopolysaccharide-Challenged Piglets.
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ABSTRACT:
SUBMITTER: Duan Y
PROVIDER: S-EPMC8035022 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:The present study is aimed to explore the effects of different dietary beta-hydroxy-beta-methyl butyrate (HMB) levels (0, 0.05%, 0.10%, or 0.15%) on liver lipid metabolism on Wenshi broiler chickens. Results showed that HMB reduced the liver weight as well as liver concentrations of triacylglycerol (TG) and total cholesterol (TC) (quadratically, p < 0.05), and the lowest values were observed in the 0.10% HMB group. Meanwhile, HMB supplementation significantly altered the expression levels of key genes related to lipid metabolism in the liver of broiler chickens (p < 0.05). Furthermore, 16S rRNA gene sequencing revealed that HMB supplementation could greatly change the richness, diversity, and composition of the broiler gut microbiota, and the Bacteroidetes relative abundance at the phylum level and the Alistipes relative abundance at the genus level were affected (p < 0.05). Correlation analysis further suggested a strong association between Bacteroidetes relative abundance and lipid metabolism-related parameters (p < 0.05). Together, these data suggest that 0.10% HMB supplementation could inhibit hepatic fat deposition via regulating gut microbiota in broilers.
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Project description:BackgroundGalacto-oligosaccharides (GOS) are non-digestible food ingredients that promote the growth of beneficial bacteria in the gut. This study investigated the protective effect of the early-life GOS supplement on the piglets' gut function against the oxidative stress induced by lipopolysaccharide (LPS)-challenge.MethodsEighteen neonatal piglets were assigned to three groups including CON, LPS and LPS + GOS groups. The piglets in CON group and LPS group received physiological saline, while those in LPS + GOS group received GOS solution for 13 d after birth. On d 14, the piglets in LPS group and LPS + GOS group were injected with LPS solutions, while the piglets in CON group were injected with the same volume of physiological saline.ResultsThe results showed that the early-life GOS supplement blocked the LPS-induced reactive oxygen species (ROS) secretion, malondialdehyde (MDA) production and the increase of pro-apoptotic factor expression. Meanwhile, the early-life GOS supplement improved the activities of antioxidant enzymes, disaccharidase enzymes activities, and digestive enzymes activities, and increased the mRNA abundance of the gene related to nutrient digestion and absorption and the relative protein expression of tight junction. The study also showed that the early-life GOS supplement improved the expression of Hemeoxygenase-1 (HO-1) and NAD(P)H/quinone acceptor oxidoreductase-1 (NQO-1), and activated the AMP-activated protein kinase (AMPK).ConclusionsThese results suggested that GOS enhanced the gut function, reduced the ROS production and pro-apoptotic factors gene expression, and activated the AMPK signaling pathway in LPS-challenged piglets.
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Project description:This study aimed to investigate the effects of chitooligosaccharide (COS) on intestinal barrier, antioxidant capacity, and immunity of lipopolysaccharide (LPS)-challenged laying hens. A total of 360 Hy-line Brown laying hens (80-wk-old) were randomly divided into 5 groups with 6 replicates of 12 birds. Hens were fed a corn-soybean meal basal diet supplemented with different COS levels (0; 5; 10; 15; 20 mg/kg) for 8 wk. The results showed that 15 mg/kg COS administration elevated albumen height and Haugh unit (P < 0.05), and numerically optimized productive performance (P > 0.05), therefore, the dosage of 15 mg/kg was chosen for the subsequent experiment. Thereafter, 12 birds from non-supplemented group were randomly selected and assigned into 2 groups, and birds in each group were administered (1.5 mg/kg BW, i.p.) with saline (control group) or LPS (challenge group). Another 6 hens from 15 mg/kg COS-supplemented group were selected and injected with LPS in the same way. Compared with the control group, LPS-challenged birds exhibited elevated circulating diamine oxidase activity, and reduced jejunal villus height and ratio of villus height to crypt depth, and these indices were reversed to control levels by COS (P < 0.05). Also, LPS increased malondialdehyde accumulation and reduced several antioxidant enzyme activities in the intestinal mucosa (P < 0.05). Additionally, LPS increased jejunal secretory IgA and interferon-γ (IFN-γ), and ileal secretory IgA, IgM, and interleukin-1β (IL-1β) concentrations, whereas COS reduced jejunal IFN-γ and IL-1β, and ileal IgM levels (P < 0.05). Moreover, LPS down-regulated mRNA abundance of jejunal occludin and claudin 2, and upregulated expression of jejunal nuclear factor erythroid-2 related factor 2, superoxide dismutase 1, and IFN-γ as well as ileal IL-1β (P < 0.05). Besides, COS increased jejunal occludin and ileal claudin 2, nuclear factor erythroid-2 related factor 2, and heme oxygenase-1 expression, and decreased jejunal IFN-γ and IL-1β abundance (P < 0.05). These results suggested that COS could alleviate LPS-induced intestinal barrier impairment, and oxidative and immunological stress in laying hens.
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Project description:ObjectiveThis study was designed to investigate the hypothesis that dietary quercetin (QUE) and coated sodium butyrate (SB) supplementation alleviate oxidative stress in the small intestine of diquat (DIQ)-challenged pullets.MethodsA total of 200 13-week-old pullets were divided into four groups: the control group (CON), the DIQ group, the QUE group, and the coated SB group, and injected intraperitoneally with either saline (CON) or diquat (DIQ, QUE, and SB) to induce oxidative stress on day 0.ResultsOn the first day, the malondialdehyde and superoxide dismutase (SOD) concentrations in the SB group were significantly different from those in the DIQ and QUE groups (p<0.05), and dietary supplementation with SB increased serum glutathione peroxidase (GSH-PX) levels compared with the DIQ group (p<0.05). Quercetin and SB increased the levels of CLAUDIN-1 and zonula occludens-1 (ZO-1) in the jejunum. On the tenth day of treatment, QUE attenuated the decrease in GSH-PX levels compared to those of the CON group (p<0.05), while SB increased SOD, GSH-PX, and total antioxidant capacity levels compared to those of the DIQ group. Nuclear factor erythroid 2-related factor 2 (NRF2) and heme oxygenase-1 (HO-1) mRNA levels in the QUE and SB groups increased (p<0.05) and CLAUDIN-1 mRNA levels in the QUE and SB groups were upregulated compared to those in the DIQ group ileum tissue.ConclusionSupplementation of QUE and SB demonstrated the ability to relieve oxidative stress in pullets post DIQ-injection with a time-dependent manner and QUE and SB may be potential antioxidant additives for relieving oxidative stress and protecting the intestinal barrier of pullets.
| S-EPMC9449397 | biostudies-literature
Project description:Two experiments were conducted to investigate the effects of exogenous catalase (CAT) in the diet of weaned piglets on growth performance, oxidative capacity, and hepatic apoptosis after challenge with lipopolysaccharide (LPS). In experiment 1, 72 weaned piglets [Duroc × Landrace × Yorkshire, 6.90 ± 0.01 kg body weight (BW), 21 d of age] were randomly assigned to be fed either a basal diet (CON group) or a basal diet supplemented with 2,000 mg/kg CAT (CAT group; dietary CAT activity, 120 U/kg) for 35 d. Blood samples were collected on day 21 and day 35. At the end of this experiment, 12 pigs were selected from each of the CON and CAT groups, and six pigs were injected with LPS (50 μg/kg BW), while the remaining six pigs were injected with an equal amount of sterile saline, resulting in a 2 × 2 factorial arrangement of treatments (experiment 2). Blood samples and rectal temperature data were collected 0 and 4 h after challenge, and liver samples were obtained after evisceration. The gain-to-feed ratio was higher (P < 0.05) in piglets in the CAT group than in those in the CON group from day 1 to 35. Catalase and total superoxide dismutase (T-SOD) activities were higher (P < 0.05), whereas malondialdehyde (MDA) concentrations were lower (P < 0.05), in piglets in the CAT group than in those in the CON group at day 35. During challenge, rectal temperature and liver MDA and H2O2 concentrations increased significantly (P < 0.05), whereas plasma CAT and glutathione peroxidase (GSH-Px) activities and liver CAT activity decreased markedly (P < 0.05), in LPS-challenged piglets 4 h post-challenge. Increased CAT activity and decreased MDA concentration were observed in the plasma and liver of piglets in the CAT group 4 h post-challenge (P < 0.05). Dietary CAT supplementation markedly suppressed the LPS-induced decrease in plasma GSH-Px activity and liver CAT activity to levels observed in the CON group (P < 0.05) as well as significantly decreasing the concentration and mRNA expression of caspase-3 and caspase-9 (P < 0.05). LPS-induced liver injury was also attenuated by dietary CAT supplementation, as demonstrated by a decrease in liver caspase-3 mRNA expression (P < 0.05). Overall, dietary supplementation with 2,000 mg/kg exogenous CAT (dietary CAT activity, 120 U/kg) improves growth performance and has a beneficial effect on antioxidant capacity in weaned piglets; alleviates oxidative stress and reduces liver damage by suppressing hepatic apoptosis in LPS-challenged piglets.
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Project description:Sarcopenia is a frequent complication in liver transplant (LT) recipients. β-hydroxy-β-methyl-butyrate (HMB) has the potential to increase muscle-performance and tropism. Our study aims at evaluating the effect on muscle mass and functioning, and the safety of 12 weeks of HMB supplementation in patients after LT. This is a pilot, randomized study. Male patients undergoing LT were randomly assigned to the HMB or control group. A diet interview, anthropometry and body composition by dual energy X-ray absorptiometry (DEXA) were performed at enrollment (T0), after 12 weeks (T1) and after 12 months (T12). Twenty-two liver transplant male patients were enrolled in the study: 12 in the HMB group and 10 as the control group. At enrollment, demographic, clinical and nutritional data were similar. According to the appendicular skeletal muscle index, sarcopenia was present in 50% of patients. The appendix skeletal muscle mass index (ASMI) showed a significant increase at T1 and T12 in HMB patients, but not in controls. The mid-arm muscle-circumference and hand grip strength also increased at T1 and T12 versus T0 only in the HMB group. No side effects were reported in either group. The study showed a positive effect of HMB in the recovery of muscle mass and strength after LT. HMB supplement in patients after LT was safe and well tolerated.
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Project description:β-Hydroxy-β-Methyl Butyrate (HMB) is a natural catabolite of leucine deemed to play a role in amino acid signaling and the maintenance of lean muscle mass. Accordingly, HMB is used as a dietary supplement by sportsmen and has shown some clinical effectiveness in preventing muscle wasting in cancer and chronic lung disease, as well as in age-dependent sarcopenia. However, the molecular cascades underlying these beneficial effects are largely unknown. HMB bears a significant structural similarity with Butyrate and β-Hydroxybutyrate (βHB), two compounds recognized for important epigenetic and histone-marking activities in multiple cell types including muscle cells. We asked whether similar chromatin-modifying actions could be assigned to HMB as well. Exposure of murine C2C12 myoblasts to millimolar concentrations of HMB led to an increase in global histone acetylation, as monitored by anti-acetylated lysine immunoblotting, while preventing myotube differentiation. In these effects, HMB resembled, although with less potency, the histone deacetylase (HDAC) inhibitor Sodium Butyrate. However, initial studies did not confirm a direct inhibitory effect of HMB on HDACs in vitro. β-Hydroxybutyrate, a ketone body produced by the liver during starvation or intense exercise, has a modest effect on histone acetylation of C2C12 cells or in vitro HDAC inhibitor activities, and, unlike Butyrate and HMB, did not interfere with myotube formation in a myoblast differentiation assay. Instead, βHB dramatically increased lysine β-hydroxybutyrylation (Kbhb) of histone tails, an epigenetic mark associated with fasting responses and muscle catabolic states. However, when C2C12 cells were exposed to βHB in the presence of equimolar HMB this chromatin modification was drastically reduced, pointing to a role for HMB in attenuating ketosis-associated muscle wasting. In conclusion, while their mechanistic underpinnings remain to be clarified, these preliminary observations highlight novel and potentially important activities of HMB as an epigenetic regulator and βHB antagonist in muscle precursor cells, to be further explored in their biomedical implications.
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Project description:BackgroundWeanling pigs, with immature immune system and physiological function, usually experience post-weaning diarrhea. This study determined the effects of dietary Clostridium butyricum supplementation on growth performance, diarrhea, and immunity of weaned pigs challenged with lipopolysaccharide (LPS).MethodsIn Experiment (Exp.) 1, 144 weaned piglets were weaned at 21 d and randomly assigned to six groups, with six replicates per group and four pigs per replicate, receiving a control diet (CON) or diet supplemented with antibiotics (AB) or C. butyricum (CB) (0.1%, 0.2%, 0.4%, or 0.8%), respectively. All diets in Exp. 1 were a highly digestible basal diet, with 3,000 mg/kg zinc oxide supplied in the first 2 wk only. In Exp. 2, 180 piglets were weaned at 21 d and randomly assigned to five groups, with six replicates per group and six pigs per replicate, receiving CON, AB, or CB (0.2%, 0.4%, or 0.6%) diets. The digestibility of diets was lower than those in Exp. 1, and did not include zinc oxide. At 36 d of Exp. 2, 12 piglets were selected from each of the CON and 0.4% CB groups, six piglets were intraperitoneally injected with LPS (50 μg/kg body weight) and the other six piglets with normal saline; animals were killed at 4 h after injection to collect blood, intestine, and digesta samples for biochemical analysis.ResultsIn Exp. 1, CB and AB diets had no effect on growth performance of piglets. In Exp. 2, 0.4% CB decreased feed-gain ratio (P < 0.1), diarrhea score (P < 0.05), and increased duodenal, jejunal, and ileal villus height and jejunal villus height/crypt depth (P < 0.05). The 0.4% CB decreased the plasma tumor necrosis factor (TNF) α (P < 0.05) but increased ileal mucosa IL-10 and TLR2 mRNA expression (P < 0.05). Furthermore, 0.4% CB altered the microbial profile, with Bacillus and Ruminococcaceae UGG-003 at genus level and Lactobacillus casei and Parasutterella secunda at species level were higher than CON in colonic content (P < 0.05).ConclusionsDietary C. butyricum supplementation had positive effects on growth of weaned piglets with less digestible diets. There was a tendency to reduce the feed-gain ratio, which could reduce feed costs in pig production. Moreover, C. butyricum decreased post-weaning diarrhea by improving the intestinal morphology, intestinal microflora profile, and immune function.
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Project description:This study aimed to evaluate the effects of maternal nucleotide (NT) supplementation on intestinal morphology and immune function in lipopolysaccharide-challenged newborn piglets. At 85 d gestation, 12 sows were selected and assigned to two groups: the CON group (basal diet, n = 6) and the NT group (basal diet with 1 g/kg NT mixture, n = 6). After parturition, newborn piglets were collected without suckling. Piglets from the CON group were intraperitoneally injected with sterile saline or lipopolysaccharide (LPS, 10 mg/kg body weight), and divided into the C-CON (n = 6) and C-LPS groups (n = 6). Piglets from the NT group received the same treatment and were divided into the N-CON (n = 6) and N-LPS groups (n = 6). The blood and small intestinal samples of piglets were collected 1 h after injection. The results showed that: (1) maternal NT supplementation increased the concentrations of serum complement C3 and C4 (P < 0.05), and suppressed the increase in serum hypersensitive C-reactive protein in LPS-challenged newborn piglets (P < 0.05); (2) maternal NT supplementation increased the villus height and the ratio of villus height to crypt depth in the duodenum of newborn piglets (P < 0.05) and inhibited the LPS-induced decrease in the villus height in the jejunum and ileum (P < 0.05). (3) The LPS-induced increased levels of interleukin-6 in the jejunum and tumor necrosis factor-α in the ileum of newborn piglets were suppressed by maternal NT supplementation (P < 0.05). (4) In the jejunum of newborn piglets, maternal NT supplementation inhibited the LPS-induced increase in toll-like receptor 4 (TLR4) mRNA and protein expression (P < 0.05) and the decrease of nuclear factor-κB inhibitor α (IκBα) protein expression (P < 0.05). In the ileum, piglets had a lower nuclear factor-κB (NFκB) mRNA expression in the NT groups than the CON groups (P < 0.05), and maternal NT supplementation suppressed the decrease of IκBα mRNA in LPS-treated piglets (P < 0.05). In conclusion, maternal NT supplementation could promote the intestinal development and immune function of newborn piglets, and may improve LPS-induced intestinal inflammatory responses via the TLR4/IκBα/NFκB pathway.
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Project description:This study aimed to investigate the effects of dietary beta-hydroxy beta-methyl butyrate (HMB) supplementation on muscular lipid metabolism in Bama Xiang mini-pigs. Thirty-two piglets (8.58 ± 0.40 kg, barrow) were selected and fed a basal diet supplemented either with 0 (control), 0.13%, 0.64%, or 1.28% HMB for 60 days. Throughout the experiments, they had free access to clean drinking water and diets. Data of this study were analyzed by one-way ANOVA using the SAS 8.2 software package, followed by a Tukey's studentized range test to explore treatment effects. The results showed that compared to the control, 0.13% HMB decreased the intramuscular fat (IMF) content and increased polyunsaturated fatty acids (PUFAs) in Longissimus thoracis muscle (LTM), and increased the n3 PUFAs in soleus muscles (SM, p < 0.05). Moreover, HMB supplementation led to alterations in the mRNA expression of genes related to lipid metabolism. Serum metabolome profiling showed that in both LTM and SM of Bama Xiang mini-pigs, N-Methyl-l-glutamate was positively correlated with SFA and nummularine A was negatively correlated with C18:3n3 PUFA (p < 0.05). Therefore, N-Methyl-l-glutamate and nummularine A might be potential biomarkers of the HMB-supplemented group. These results suggested that dietary HMB supplementation could decrease the IMF content and increase n3 PUFAs as well as regulate the related metabolites (N-Methyl-l-glutamate and nummularine A) in the serum of pigs.
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