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Huang M, Ma Y, Fan Q, Che S, Zhang J, Ding S, Zhu S, Li X. Effects of nanopolystyrene and/or phoxim exposure on digestive function of Eriocheir sinensis. Comp Biochem Physiol C Toxicol Pharmacol 2025; 289:110102. [PMID: 39653099 DOI: 10.1016/j.cbpc.2024.110102] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/29/2024] [Revised: 12/04/2024] [Accepted: 12/05/2024] [Indexed: 12/12/2024]
Abstract
Nanopolystyrene (NP) and phoxim (PHO) are pervasive environmental contaminants that pose a significant threat to the health of aquatic organisms, prompting widespread concern among researchers and the public alike. The hepatopancreas play important roles in the Chinese mitten crab (Eriocheir sinensis), such as digestion, absorption and detoxification. This study assessed the hepatopancreatic toxicity caused by the exposure of Eriocheir sinensis to environmentally relevant concentrations of NP and/or PHO. After a 21-day exposure period, NP (1.0 × 1010 particles/L) and PHO (24 μg/L) exposure resulted in reduced number of blister-like, resorptive, and fibrillar cells and an elevation in lipid droplets within the hepatopancreas compared to the control group. Furthermore, trypsin and lipase activity decreased, amylase activity increased, and a significantly decrease in the expression of digestion-related genes, including CHT, CarL, and CarB, suggested impairment in both digestive and metabolic functions. The marked upregulation of key genes, including PPARγ, GYK, PEPCK, and SCD, as well as key metabolites such as 4-methylzymosterol-carboxylate, zymosterone, lathosterol, 7-dehydro-desmosterol, vitamin D2, 24-methylene-cycloartanol, 5-dehydroepisterol, and sitosterol in the lipid metabolic pathway, showed that the peroxisome proliferator-activated receptor (PPAR) and steroid biosynthesis signaling pathways were highly affected by exposure to NP and/or PHO. These findings indicated that exposure to NP and/or PHO might adversely affect the hepatopancreatic physiological homeostasis in E. sinensis by causing tissue damage and interfering with digestive and metabolic functions. Our results provide ecotoxicological insights into the effects of nanopolystyrene and/or phoxim exposure on the digestive function of Eriocheir sinensis.
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Affiliation(s)
- Mengting Huang
- College of Animal Science and Technology, Anhui Agricultural University, Hefei 230036, China
| | - Yuan Ma
- College of Animal Science and Technology, Anhui Agricultural University, Hefei 230036, China
| | - Qianru Fan
- College of Animal Science and Technology, Anhui Agricultural University, Hefei 230036, China
| | - Shunli Che
- College of Animal Science and Technology, Anhui Agricultural University, Hefei 230036, China
| | - Jun Zhang
- College of Animal Science and Technology, Anhui Agricultural University, Hefei 230036, China; Engineering Technology Research Center of Healthy Aquaculture, Anhui Agricultural University, Hefei 230036, China
| | - Shuquan Ding
- College of Animal Science and Technology, Anhui Agricultural University, Hefei 230036, China; Engineering Technology Research Center of Healthy Aquaculture, Anhui Agricultural University, Hefei 230036, China
| | - Shuren Zhu
- Shandong Freshwater Fisheries Research Institute, Jinan 250013, China.
| | - Xilei Li
- College of Animal Science and Technology, Anhui Agricultural University, Hefei 230036, China; Engineering Technology Research Center of Healthy Aquaculture, Anhui Agricultural University, Hefei 230036, China.
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Guo L, Zheng C, Chen J, Du R, Li F. Phenylalanine Regulates Milk Protein Synthesis via LAT1-mTOR Signaling Pathways in Bovine Mammary Epithelial Cells. Int J Mol Sci 2024; 25:13135. [PMID: 39684845 DOI: 10.3390/ijms252313135] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2024] [Revised: 11/12/2024] [Accepted: 12/03/2024] [Indexed: 12/18/2024] Open
Abstract
Phenylalanine (Phe) is a potentially limiting amino acid for lactating cows. The mechanism by which Phe regulates milk protein synthesis remains unclear. The present study elucidates the mechanisms by which phenylalanine affects milk protein synthesis, amino acid utilization, and related signaling pathways in bovine mammary epithelial cells (BMECs). The BMECs were treated with five concentrations (0, 0.22, 0.44, 0.88, 1.76 mM, and serum free). Rapamycin inhibitors and RNA interference (RNAi) were used to inhibit the phosphorylation of the mammalian target of rapamycin (mTOR) signaling pathway and the expression of relevant amino acid transporters, respectively. The results showed that 4×Phe (0.88 mM) significantly increased (p < 0.05) both the mRNA and protein expression of α-casein (CSN1S1), β-casein (CSN2), and κ-casein (CSN3), as well as L-type amino acid transporter-1 (LAT1) mRNA expression. Protein expression and modification assays of mTOR-related proteins showed that 4×Phe could increase (p < 0.05) the expression of α-casein and eukaryotic initiation factor 4E-binding protein-1 (4EBP1) and tended to increase the expression of ribosomal protein S6 protein kinase (S6K1, p = 0.054). The general control nonderepressible 2 (GCN2) signaling pathway factor, eukaryotic initiation factor 2 (eIF2α), was downregulated by 4×Phe treatment (p < 0.05). The rapamycin inhibition test showed that Phe regulated casein synthesis via the mTOR signaling pathway. RNAi experiments showed that LAT1 mediated the entry of Phe into cells. Moreover, 4×Phe treatment tended to decrease (0.05 < p < 0.10) the consumption of valine, leucine, histidine, tyrosine, cysteine, alanine, asparagine, and serine in the medium. Collectively, phenylalanine enhanced α-casein synthesis by regulating the phosphorylation of 4EBP1 and eIF2α and promoting the formation of the mTOR-centered casein translation initiation complex.
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Affiliation(s)
- Long Guo
- State Key Laboratory of Herbage Improvement and Grassland Agro-Ecosystems, College of Pastoral Agriculture Science and Technology, Lanzhou University, Lanzhou 730020, China
| | - Chen Zheng
- Animal Nutrition Group, Wageningen University, 6700 AH Wageningen, The Netherlands
| | - Jiao Chen
- State Key Laboratory of Herbage Improvement and Grassland Agro-Ecosystems, College of Pastoral Agriculture Science and Technology, Lanzhou University, Lanzhou 730020, China
| | - Ruifang Du
- State Key Laboratory of Herbage Improvement and Grassland Agro-Ecosystems, College of Pastoral Agriculture Science and Technology, Lanzhou University, Lanzhou 730020, China
| | - Fei Li
- State Key Laboratory of Herbage Improvement and Grassland Agro-Ecosystems, College of Pastoral Agriculture Science and Technology, Lanzhou University, Lanzhou 730020, China
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Crouse MS, Trotta RJ, Freetly HC, Lindholm-Perry AK, Neville BW, Oliver WT, Hammer CJ, Syring JG, King LE, Neville TL, Reynolds LP, Dahlen CR, Caton JS, Ward AK, Cushman RA. Disrupted one-carbon metabolism in heifers negatively affects their health and physiology. J Anim Sci 2024; 102:skae144. [PMID: 38770669 PMCID: PMC11176977 DOI: 10.1093/jas/skae144] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2024] [Accepted: 05/20/2024] [Indexed: 05/22/2024] Open
Abstract
The objective of this study was to determine the dose-dependent response of one-carbon metabolite (OCM: methionine, choline, folate, and vitamin B12) supplementation on heifer dry matter intake on fixed gain, organ mass, hematology, cytokine concentration, pancreatic and jejunal enzyme activity, and muscle hydrogen peroxide production. Angus heifers (n = 30; body weight [BW] = 392.6 ± 12.6 kg) were individually fed and assigned to one of five treatments: 0XNEG: total mixed ration (TMR) and saline injections at days 0 and 7 of the estrous cycle, 0XPOS: TMR, rumen-protected methionine (MET) fed at 0.08% of the diet dry matter, rumen-protected choline (CHOL) fed at 60 g/d, and saline injections at days 0 and 7, 0.5X: TMR, MET, CHOL, 5-mg B12, and 80-mg folate injections at days 0 and 7, 1X: TMR, MET CHOL, 10-mg vitamin B12, and 160-mg folate at days 0 and 7, and 2X: TMR, MET, CHOL, 20-mg vitamin B12, and 320-mg folate at days 0 and 7. All heifers were estrus synchronized but not bred, and blood samples were collected on days 0, 7, and at slaughter (day 14) during which tissues were collected. By design, heifer ADG did not differ (P = 0.96). Spleen weight and uterine weight were affected cubically (P = 0.03) decreasing from 0XPOS to 0.5X. Ovarian weight decreased linearly (P < 0.01) with increasing folate and B12 injection. Hemoglobin and hematocrit percentage were decreased (P < 0.01) in the 0.5X treatment compared with all other treatments. Plasma glucose, histotroph protein, and pancreatic α-amylase were decreased (P ≤ 0.04) in the 0.5X treatment. Heifers on the 2X treatment had greater pancreatic α-amylase compared with 0XNEG and 0.5X treatment. Interleukin-6 in plasma tended (P = 0.08) to be greater in the 0XPOS heifers compared with all other treatments. Lastly, 0XPOS-treated heifers had reduced (P ≤ 0.07) hydrogen peroxide production in muscle compared with 0XNEG heifers. These data imply that while certain doses of OCM do not improve whole animal physiology, OCM supplementation doses that disrupt one-carbon metabolism, such as that of the 0.5X treatment, can induce a negative systemic response that results in negative effects in both the dam and the conceptus during early gestation. Therefore, it is necessary to simultaneously establish an optimal OCM dose that increases circulating concentrations for use by the dam and the conceptus, while avoiding potential negative side effects of a disruptive OCM, to evaluate the long-term impacts of OCM supplementation of offspring programming.
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Affiliation(s)
- Matthew S Crouse
- USDA, ARS, U.S. Meat Animal Research Center, Clay Center, NE 68933, USA
| | - Ronald J Trotta
- Department of Animal and Food Sciences, University of Kentucky, Lexington, KY 40546, USA
| | - Harvey C Freetly
- USDA, ARS, U.S. Meat Animal Research Center, Clay Center, NE 68933, USA
| | | | - Bryan W Neville
- USDA, ARS, U.S. Meat Animal Research Center, Clay Center, NE 68933, USA
| | - William T Oliver
- USDA, ARS, U.S. Meat Animal Research Center, Clay Center, NE 68933, USA
| | - Carrie J Hammer
- Department of Animal Sciences, and Center for Nutrition and Pregnancy, North Dakota State University, Fargo, ND 58108, USA
| | - Jessica G Syring
- Department of Animal Sciences, and Center for Nutrition and Pregnancy, North Dakota State University, Fargo, ND 58108, USA
| | - Layla E King
- Department of Agriculture and Natural Resources, University of Minnesota Crookston, Crookston, MN 56716, USA
| | - Tammi L Neville
- Department of Animal Sciences, and Center for Nutrition and Pregnancy, North Dakota State University, Fargo, ND 58108, USA
| | - Lawrence P Reynolds
- Department of Animal Sciences, and Center for Nutrition and Pregnancy, North Dakota State University, Fargo, ND 58108, USA
| | - Carl R Dahlen
- Department of Animal Sciences, and Center for Nutrition and Pregnancy, North Dakota State University, Fargo, ND 58108, USA
| | - Joel S Caton
- Department of Animal Sciences, and Center for Nutrition and Pregnancy, North Dakota State University, Fargo, ND 58108, USA
| | - Alison K Ward
- Department of Veterinary Biomedical Science, University of Saskatchewan, Saskatoon, SK S7N5A2, Canada
| | - Robert A Cushman
- USDA, ARS, U.S. Meat Animal Research Center, Clay Center, NE 68933, USA
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Han D, Shi L, Yu J, Na L. Effects of soda water on blood lipid and metabolic profiling of urine in hyperlipidemia rats using UPLC/Triple-TOF MS. Heliyon 2023; 9:e21666. [PMID: 38027945 PMCID: PMC10643294 DOI: 10.1016/j.heliyon.2023.e21666] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2023] [Revised: 10/23/2023] [Accepted: 10/25/2023] [Indexed: 12/01/2023] Open
Abstract
The effects of a natural soda water (Shi Han Quan, SHQ) on hyperlipidemia and the changes of urine metabolic profiling by metabolomics techniques were investigate. Thirty six Wistar rats weighing 160-200 g were divided into control group, hyperlipidemia (HL) group, and hyperlipidemia + SHQ water (SHQ) group. The metabolites in urine were determined using ultra high performance liquid chromatography-triple-time of flight-mass spectrometry (UPLC/Triple-TOF MS). At the end of 1 month and 3 months, the total glyceride (TG) level was significantly lower in SHQ group compared to HL group. There was no significantly difference in total cholesterol (TC) levels in HL group compared with SHQ group. The results showed that dinking SHQ water can improve the TG, but with no effects on TC. After drinking SHQ water for 3 months, the rats in different groups could be classified into different clusters according to the metabolites in urine. Total 15 important metabolites were found and correlated with disturbance of amino acid, phospholipid, fatty acid and vitamin metabolism, which suggested the changes of metabolism in the body and possible mechanism by which SHQ improved the TG. These findings provide a new insight for the prevention and control of hyperlipidemia.
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Affiliation(s)
- Dan Han
- Department of Research, Shanghai University of Medicine & Health Sciences Affiliated Zhoupu Hospital, The College of Medical Technology, Shanghai University of Medicine & Health Sciences, Shanghai, 201318, China
| | - Litian Shi
- Harbin Greenstone Water Research Institute, Harbin, 150009, China
| | - Junjie Yu
- Department of Endocrinology, Second Affiliated Hospital, Harbin Medical University, Harbin, 150001, China
| | - Lixin Na
- The College of Public Health, Shanghai University of Medicine & Health Sciences, Shanghai, 201318, China
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Trotta RJ, Swanson KC, Klotz JL, Harmon DL. Postruminal Casein Infusion and Exogenous Glucagon-Like Peptide 2 Administration Differentially Stimulate Pancreatic α-Amylase and Small Intestinal α-Glucosidase Activity in Cattle. J Nutr 2023; 153:2854-2867. [PMID: 37573014 DOI: 10.1016/j.tjnut.2023.08.009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2023] [Revised: 08/01/2023] [Accepted: 08/04/2023] [Indexed: 08/14/2023] Open
Abstract
BACKGROUND Increasing luminal carbohydrate flow decreases pancreatic α-amylase activity but can increase jejunal maltase activity, suggesting that regulation of carbohydrase activity is perhaps uncoordinated in response to luminal carbohydrate flow. Increasing luminal casein flow increases pancreatic α-amylase activity in cattle, and exogenous glucagon-like peptide 2 (GLP-2) has been shown to increase small intestinal α-glucosidase activity in nonruminants. OBJECTIVES The objective was to evaluate the effects of postruminal casein infusion, exogenous GLP-2, or their combination on endogenous pancreatic and small intestinal carbohydrase activity in cattle postruminally infused with starch. METHODS Holstein steers [n = 24; 250 ± 23 kg body weight (BW)] received a continuous abomasal infusion of 3.94 g raw corn starch/kg of BW combined with either 0 or 1.30 g casein/kg of BW. Steers received subcutaneous injections in 2 equal portions daily of excipient (0.5% bovine serum albumin) or 100 μg GLP-2/kg of BW per day. At the end of the 7-d treatment period, steers were slaughtered for tissue collection. Data were analyzed using the MIXED procedure of SAS version 9.4 (SAS Institute Inc.). RESULTS Postruminal casein infusion increased (P ≤ 0.03) pancreatic mass by 12.6%, total pancreatic α-amylase activity by 50%, and postruminal starch disappearance from 96.7% to 99.3%. Exogenous GLP-2 increased (P < 0.01) total small intestinal and mucosal mass by 1.2 kg and 896 g, respectively. Relative to control, GLP-2 and casein + GLP-2 increased (P = 0.04) total small intestinal α-glucosidase activity by 83.5%. Total small intestinal maltase, isomaltase, and glucoamylase activity was 90%, 100%, and 66.7% greater for GLP-2 and casein + GLP-2 steers compared with control. CONCLUSIONS Casein increased pancreatic α-amylase activity, GLP-2 increased small intestinal α-glucosidase activity, and the combination of casein and GLP-2 increased both pancreatic α-amylase activity and small intestinal α-glucosidase activity. This novel approach provides an in vivo model to evaluate effects of increasing endogenous carbohydrase activity on small intestinal starch digestion.
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Affiliation(s)
- Ronald J Trotta
- Department of Animal and Food Sciences, University of Kentucky, Lexington, KY, United States
| | - Kendall C Swanson
- Department of Animal Science, North Dakota State University, Fargo, ND, United States
| | - James L Klotz
- Forage-Animal Production Research Unit, USDA, ARS, Lexington, KY, United States
| | - David L Harmon
- Department of Animal and Food Sciences, University of Kentucky, Lexington, KY, United States.
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Li Y, Mei J, Wang J, Liu H. Effects of dandelion (Taraxacum sp.,) supplements on lactation performance, antioxidative activity, and plasma metabolome in primiparous dairy cows. Anim Biosci 2023; 36:229-237. [PMID: 36108692 PMCID: PMC9834724 DOI: 10.5713/ab.22.0061] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2022] [Accepted: 08/05/2022] [Indexed: 12/24/2022] Open
Abstract
OBJECTIVE This study evaluated the effects of dandelion supplements on lactation performance, circulating antioxidative activity and plasma metabolomics in primiparous dairy cows. METHODS A total of 60 mid-lactation dairy cows (milk yield = 34.29±0.34 kg/d; days in milk = 151.72±2.36 days) were divided into 4 treatment groups randomly, comprising the addition of dandelion at 0, 100, 200, 400 g/d per head. The experiment lasted for 8 weeks with an extra 10 days' pre-feeding period. Milk and blood samples were collected, and plasma samples were selected to perform metabolomics analysis. RESULTS Supplementing 200 g/d of dandelion increased the yield of milk and lactose (p≤ 0.05). The milk somatic cell counts (p≤0.05) were lower in all dandelion groups than those in the control group. The activity of glutathione peroxidase (p≤0.05) and superoxide dismutase (p≤0.05) were increased and plasma malondialdehyde (p = 0.01) was decreased when cows were fed 200 g/d dandelion. Plasma metabolomics analysis showed that 23 hub differential metabolites were identified in the 200 g/d dandelion group. These metabolites such as ribose, glutamic acid, valine, and phenylalanine were enriched in D-glutamine and D-glutamate metabolism (p = 0.06, impact value = 1), phenylalanine, tyrosine, and tryptophan biosynthesis (p = 0.05, impact value = 0.5), and starch and sucrose metabolism (p = 0.21, impact value = 0.13). Moreover, correlation analysis showed that circulating ribose, mannose, and glutamic acid were positively related to milk yield. CONCLUSION Dandelion supplementation could improve lactation performance and elevate the plasma carbohydrate and amino acids metabolism and antioxidative activity. Supplementation of 200 g/d dandelion is recommended for lactating dairy cows.
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Affiliation(s)
- Yan Li
- College of Animal Sciences, Zhejiang University, Hangzhou 310058,
China
| | - Jie Mei
- College of Animal Sciences, Zhejiang University, Hangzhou 310058,
China
| | - Jiaqi Wang
- College of Animal Sciences, Zhejiang University, Hangzhou 310058,
China
| | - Hongyun Liu
- College of Animal Sciences, Zhejiang University, Hangzhou 310058,
China,Corresponding Author: Hongyun Liu, Tel: +86-571-8898-2965, Fax: +86-571-8898-2930, E-mail:
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Brauneck F, Fischer B, Witt M, Muschhammer J, Oelrich J, da Costa Avelar PH, Tsoka S, Bullinger L, Seubert E, Smit DJ, Bokemeyer C, Ackermann C, Wellbrock J, Haag F, Fiedler W. TIGIT blockade repolarizes AML-associated TIGIT + M2 macrophages to an M1 phenotype and increases CD47-mediated phagocytosis. J Immunother Cancer 2022; 10:jitc-2022-004794. [PMID: 36549780 PMCID: PMC9791419 DOI: 10.1136/jitc-2022-004794] [Citation(s) in RCA: 37] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/27/2022] [Indexed: 12/24/2022] Open
Abstract
BACKGROUND Leukemia-associated macrophages (LAMs) represent an important cell population within the tumor microenvironment, but little is known about the phenotype, function, and plasticity of these cells. The present study provides an extensive characterization of macrophages in patients with acute myeloid leukemia (AML). METHODS The phenotype and expression of coregulatory markers were assessed on bone marrow (BM)-derived LAM populations, using multiparametric flow cytometry. BM and blood aspirates were obtained from patients with newly diagnosed acute myeloid leukemia (pAML, n=59), patients in long-term remission (lrAML, n=8), patients with relapsed acute myeloid leukemia (rAML, n=7) and monocyte-derived macrophages of the blood from healthy donors (HD, n=17). LAM subpopulations were correlated with clinical parameters. Using a blocking anti-T-cell immunoreceptor with Ig and ITIM domains (TIGIT) antibody or mouse IgG2α isotype control, we investigated polarization, secretion of cytokines, and phagocytosis on LAMs and healthy monocyte-derived macrophages in vitro. RESULTS In pAML and rAML, M1 LAMs were reduced and the predominant macrophage population consisted of immunosuppressive M2 LAMs defined by expression of CD163, CD204, CD206, and CD86. M2 LAMs in active AML highly expressed inhibitory receptors such as TIGIT, T-cell immunoglobulin and mucin-domain containing-3 protein (TIM-3), and lymphocyte-activation gene 3 (LAG-3). High expression of CD163 was associated with a poor overall survival (OS). In addition, increased frequencies of TIGIT+ M2 LAMs were associated with an intermediate or adverse risk according to the European Leukemia Network criteria and the FLT3 ITD mutation. In vitro blockade of TIGIT shifted the polarization of primary LAMs or peripheral blood-derived M2 macrophages toward the M1 phenotype and increased secretion of M1-associated cytokines and chemokines. Moreover, the blockade of TIGIT augmented the anti-CD47-mediated phagocytosis of AML cell lines and primary AML cells. CONCLUSION Our findings suggest that immunosuppressive TIGIT+ M2 LAMs can be redirected into an efficient effector population that may be of direct clinical relevance in the near future.
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Affiliation(s)
- Franziska Brauneck
- Department of Oncology, Hematology and Bone Marrow Transplantation with Section Pneumology, Hubertus Wald University Cancer Center, University Medical Center Hamburg-Eppendorf, Hamburg, Germany,Mildred Scheel Cancer Career Center HaTriCS4, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Brit Fischer
- Department of Oncology, Hematology and Bone Marrow Transplantation with Section Pneumology, Hubertus Wald University Cancer Center, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Marius Witt
- Department of Oncology, Hematology and Bone Marrow Transplantation with Section Pneumology, Hubertus Wald University Cancer Center, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Jana Muschhammer
- Department of Oncology, Hematology and Bone Marrow Transplantation with Section Pneumology, Hubertus Wald University Cancer Center, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Jennyfer Oelrich
- Department of Oncology, Hematology and Bone Marrow Transplantation with Section Pneumology, Hubertus Wald University Cancer Center, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | | | - Sophia Tsoka
- Department of Informatics, Faculty of Natural and Mathematical Sciences, King's College London, London, UK
| | - Lars Bullinger
- Department of Hematology, Oncology and Tumor Immunology, Charite Universitatsmedizin Berlin, Berlin, Germany
| | - Elisa Seubert
- Department of Oncology, Hematology and Bone Marrow Transplantation with Section Pneumology, Hubertus Wald University Cancer Center, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Daniel J Smit
- Institute of Biochemistry and Signal Transduction, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Carsten Bokemeyer
- Department of Oncology, Hematology and Bone Marrow Transplantation with Section Pneumology, Hubertus Wald University Cancer Center, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Christin Ackermann
- Infectious Diseases Unit, I. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Jasmin Wellbrock
- Department of Oncology, Hematology and Bone Marrow Transplantation with Section Pneumology, Hubertus Wald University Cancer Center, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Friedrich Haag
- Institute of Immunology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Walter Fiedler
- Department of Oncology, Hematology and Bone Marrow Transplantation with Section Pneumology, Hubertus Wald University Cancer Center, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
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Zhang X, Deng Y, Hu S, Hu X, Ma J, Hu J, Hu B, He H, Li L, Liu H, Wang J. Comparative analysis of amino acid content and protein synthesis-related genes expression levels in breast muscle among different duck breeds/strains. Poult Sci 2022; 102:102277. [PMID: 36410066 PMCID: PMC9678761 DOI: 10.1016/j.psj.2022.102277] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2022] [Revised: 10/14/2022] [Accepted: 10/18/2022] [Indexed: 11/15/2022] Open
Abstract
Evidences have found important effects of breeds/strains on the content of amino acids (AAs) which is an important substrate for protein synthesis and contributes greatly to meat quality. Therefore, the objective of the present study was to compare the AAs content and protein synthesis-related genes expression levels in breast muscle of native breed (Jianchang duck (J)), hybrid strains (BH1, BH2, and MC♂ × (BGF2♂ × GF2♀)♀ (MC)), and commercial breed (Cherry Verry duck). Results showed that a total of 17 AAs (TAAs) was detected from breast muscle among 5 duck breeds/strains including 11 essential AAs (EAAs). Among these AAs, the contents of Proline, Threonine, Glutamine, Serine, Methionine, Phenylalanine, Histidine, and Cysteine were significant difference among 5 duck breeds/strains. The contents of EAAs, TAAs, and flavor AAs were higher in breast muscle of J and BH2 than those in other duck breeds/strains, and the ratio of EAAs/TAAs was higher in breast muscle of BH2. Furthermore, the expression levels of eukaryotic translation initiation factor 4E-binding protein 1, mammalian target of rapamycin, and proton-coupled amino acid transporter 1 were the highest in breast muscle of BH2, and that of solute carrier family 38 member 2 was the highest in breast muscle of J. Meanwhile, principal component analysis results showed that principal component 1 of BH1, principal component 3 of BH2, and principal component 2 of MC were positively corelated with EAAs/TAAs, and principal component 1 was positively correlated with flavor AAs and EAAs. In conclusion, compared to BH1, MC, and Cherry Verry duck, AA content was higher in breast muscle of BH2 and J, which might be associated with the higher expression levels of mammalian target of rapamycin, eukaryotic translation initiation factor 4E-binding protein 1, and proton-coupled amino acid transporter 1 in breast muscle of BH2 and solute carrier family 38 member 2 in breast muscle of J. The comparative analysis of AA content in breast muscle among different duck breeds/strains could provide an important basis for improving the nutritional value of duck meat in the breeding process.
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Affiliation(s)
- Xin Zhang
- Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Chengdu Campus, Sichuan Agricultural University, 611130, Chengdu, Sichuan, China
| | - Yan Deng
- Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Chengdu Campus, Sichuan Agricultural University, 611130, Chengdu, Sichuan, China
| | - Shenqiang Hu
- Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Chengdu Campus, Sichuan Agricultural University, 611130, Chengdu, Sichuan, China
| | - Xinyue Hu
- Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Chengdu Campus, Sichuan Agricultural University, 611130, Chengdu, Sichuan, China
| | - Jiaming Ma
- Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Chengdu Campus, Sichuan Agricultural University, 611130, Chengdu, Sichuan, China
| | - Jiwei Hu
- Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Chengdu Campus, Sichuan Agricultural University, 611130, Chengdu, Sichuan, China
| | - Bo Hu
- Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Chengdu Campus, Sichuan Agricultural University, 611130, Chengdu, Sichuan, China
| | - Hua He
- Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Chengdu Campus, Sichuan Agricultural University, 611130, Chengdu, Sichuan, China
| | - Liang Li
- Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Chengdu Campus, Sichuan Agricultural University, 611130, Chengdu, Sichuan, China
| | - Hehe Liu
- Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Chengdu Campus, Sichuan Agricultural University, 611130, Chengdu, Sichuan, China
| | - Jiwen Wang
- Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Chengdu Campus, Sichuan Agricultural University, 611130, Chengdu, Sichuan, China.
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9
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Hagen CM, Roth E, Graf TR, Verrey F, Graf R, Gupta A, Pellegrini G, Poncet N, Camargo SMR. Loss of LAT1 sex-dependently delays recovery after caerulein-induced acute pancreatitis. World J Gastroenterol 2022; 28:1024-1054. [PMID: 35431492 PMCID: PMC8968515 DOI: 10.3748/wjg.v28.i10.1024] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/22/2021] [Revised: 10/08/2021] [Accepted: 01/26/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND The expression of amino acid transporters is known to vary during acute pancreatitis (AP) except for LAT1 (slc7a5), the expression of which remains stable. LAT1 supports cell growth by importing leucine and thereby stimulates mammalian target of rapamycin (mTOR) activity, a phenomenon often observed in cancer cells. The mechanisms by which LAT1 influences physiological and pathophysiological processes and affects disease progression in the pancreas are not yet known.
AIM To evaluate the role of LAT1 in the development of and recovery from AP.
METHODS AP was induced with caerulein (cae) injections in female and male mice expressing LAT1 or after its knockout (LAT1 Cre/LoxP). The development of the initial AP injury and its recovery were followed for seven days after cae injections by daily measuring body weight, assessing microscopical tissue architecture, mRNA and protein expression, protein synthesis, and enzyme activity levels, as well as by testing the recruitment of immune cells by FACS and ELISA.
RESULTS The initial injury, evaluated by measurements of plasma amylase, lipase, and trypsin activity, as well as the gene expression of dedifferentiation markers, did not differ between the groups. However, early metabolic adaptations that support regeneration at later stages were blunted in LAT1 knockout mice. Especially in females, we observed less mTOR reactivation and dysfunctional autophagy. The later regeneration phase was clearly delayed in female LAT1 knockout mice, which did not regain normal expression of the pancreas-specific differentiation markers recombining binding protein suppressor of hairless-like protein (rbpjl) and basic helix-loop-helix family member A15 (mist1). Amylase mRNA and protein levels remained lower, and, strikingly, female LAT1 knockout mice presented signs of fibrosis lasting until day seven. In contrast, pancreas morphology had returned to normal in wild-type littermates.
CONCLUSION LAT1 supports the regeneration of acinar cells after AP. Female mice lacking LAT1 exhibited more pronounced alterations than male mice, indicating a sexual dimorphism of amino acid metabolism.
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Affiliation(s)
- Cristina M Hagen
- Institute of Physiology, University of Zurich, Zurich 8057, ZH, Switzerland
| | - Eva Roth
- Institute of Physiology, University of Zurich, Zurich 8057, ZH, Switzerland
| | - Theresia Reding Graf
- Swiss Hepato-Pancreato-Biliary Center, Department of Visceral and Transplantation Surgery, Zurich University Hospital, Zurich 8091, ZH, Switzerland
| | - François Verrey
- Institute of Physiology, University of Zurich, Zurich 8057, ZH, Switzerland
| | - Rolf Graf
- Swiss Hepato-Pancreato-Biliary Center, Department of Visceral and Transplantation Surgery, Zurich University Hospital, Zurich 8091, ZH, Switzerland
| | - Anurag Gupta
- Swiss Hepato-Pancreato-Biliary Center, Department of Visceral and Transplantation Surgery, Zurich University Hospital, Zurich 8091, ZH, Switzerland
| | - Giovanni Pellegrini
- Institute of Veterinary Pathology, University of Zurich, Zurich 8057, ZH, Switzerland
| | - Nadège Poncet
- Institute of Physiology, University of Zurich, Zurich 8057, ZH, Switzerland
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10
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Guo L, Yao J, Cao Y. Regulation of pancreatic exocrine in ruminants and the related mechanism: The signal transduction and more. ACTA ACUST UNITED AC 2021; 7:1145-1151. [PMID: 34754956 PMCID: PMC8556483 DOI: 10.1016/j.aninu.2021.09.004] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2020] [Revised: 09/08/2021] [Accepted: 09/27/2021] [Indexed: 12/11/2022]
Abstract
The unique structure of the stomach, including the rumen, reticulum, omasum, and abomasum, indicates the differences between the ruminant and monogastric animals in the digestion of nutrients. This difference is reflected in the majority of dietary nutrients that may be fermented in the rumen. Significant proteins and a certain amount of starch can flow to the small intestine apart from rumen. The initial phase of small intestinal digestion requires pancreatic digestive enzymes. In theory, the enzymatic digestion and utilization efficiency of starch in the small intestine are considerably higher than that in the rumen, but the starch digestibility in the small intestine is quite low in ruminants. Therefore, improving the digestion of nutrients, especially starch in the small intestine is more urgent for high-yield ruminants. Although the pancreas plays a central role in nutrient digestion, the progress of research investigating pancreatic exocrine regulation in the ruminant is slow due to some factors, such as the complex structure of the pancreas, the selection of experimental model and duration, and internal (hormones or ages) and external (diet) influences. The present review is based on the research findings of pancreatic exocrine regulation of dairy animals and expounded from the physiological structure of the ruminant pancreas, the factors affecting the digestion and exocrine processing of carbohydrates, and the regulatory mechanism governing this process. The review aims to better understand the characteristics of enzymatic digestion, thereby advancing pancreatic exocrine research and improving the digestion and utilization of nutrients in ruminants. Additionally, this review provides the theoretical basis for improving nutrient utilization efficiency, reducing wastage of feed resources, and promoting the efficient development of the dairy industry.
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Affiliation(s)
- Long Guo
- College of Animal Science and Technology, Northwest A&F University, Yangling Shaanxi, 712100, China.,State Key Laboratory of Grassland Agro-ecosystems of Lanzhou University, Lanzhou, 730020, China.,College of Pastoral Agriculture Science and Technology, Lanzhou University, Lanzhou, 730020, China
| | - Junhu Yao
- College of Animal Science and Technology, Northwest A&F University, Yangling Shaanxi, 712100, China
| | - Yangchun Cao
- College of Animal Science and Technology, Northwest A&F University, Yangling Shaanxi, 712100, China
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11
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Oligomeric assembly regulating mitochondrial HtrA2 function as examined by methyl-TROSY NMR. Proc Natl Acad Sci U S A 2021; 118:2025022118. [PMID: 33692127 DOI: 10.1073/pnas.2025022118] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
Human High temperature requirement A2 (HtrA2) is a mitochondrial protease chaperone that plays an important role in cellular proteostasis and in regulating cell-signaling events, with aberrant HtrA2 function leading to neurodegeneration and parkinsonian phenotypes. Structural studies of the enzyme have established a trimeric architecture, comprising three identical protomers in which the active sites of each protease domain are sequestered to form a catalytically inactive complex. The mechanism by which enzyme function is regulated is not well understood. Using methyl transverse relaxation optimized spectroscopy (TROSY)-based solution NMR in concert with biochemical assays, a functional HtrA2 oligomerization/binding cycle has been established. In the absence of substrates, HtrA2 exchanges between a heretofore unobserved hexameric conformation and the canonical trimeric structure, with the hexamer showing much weaker affinity toward substrates. Both structures are substrate inaccessible, explaining their low basal activity in the absence of the binding of activator peptide. The binding of the activator peptide to each of the protomers of the trimer occurs with positive cooperativity and induces intrasubunit domain reorientations to expose the catalytic center, leading to increased proteolytic activity. Our data paint a picture of HtrA2 as a finely tuned, stress-protective enzyme whose activity can be modulated both by oligomerization and domain reorientation, with basal levels of catalysis kept low to avoid proteolysis of nontarget proteins.
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12
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Angoa-Pérez M, Kuhn DM. Evidence for Modulation of Substance Use Disorders by the Gut Microbiome: Hidden in Plain Sight. Pharmacol Rev 2021; 73:571-596. [PMID: 33597276 PMCID: PMC7896134 DOI: 10.1124/pharmrev.120.000144] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
The gut microbiome modulates neurochemical function and behavior and has been implicated in numerous central nervous system (CNS) diseases, including developmental, neurodegenerative, and psychiatric disorders. Substance use disorders (SUDs) remain a serious threat to the public well-being, yet gut microbiome involvement in drug abuse has received very little attention. Studies of the mechanisms underlying SUDs have naturally focused on CNS reward circuits. However, a significant body of research has accumulated over the past decade that has unwittingly provided strong support for gut microbiome participation in drug reward. β-Lactam antibiotics have been employed to increase glutamate transporter expression to reverse relapse-induced release of glutamate. Sodium butyrate has been used as a histone deacetylase inhibitor to prevent drug-induced epigenetic alterations. High-fat diets have been used to alter drug reward because of the extensive overlap of the circuitry mediating them. This review article casts these approaches in a different light and makes a compelling case for gut microbiome modulation of SUDs. Few factors alter the structure and composition of the gut microbiome more than antibiotics and a high-fat diet, and butyrate is an endogenous product of bacterial fermentation. Drugs such as cocaine, alcohol, opiates, and psychostimulants also modify the gut microbiome. Therefore, their effects must be viewed on a complex background of cotreatment-induced dysbiosis. Consideration of the gut microbiome in SUDs should have the beneficial effects of expanding the understanding of SUDs and aiding in the design of new therapies based on opposing the effects of abused drugs on the host's commensal bacterial community. SIGNIFICANCE STATEMENT: Proposed mechanisms underlying substance use disorders fail to acknowledge the impact of drugs of abuse on the gut microbiome. β-Lactam antibiotics, sodium butyrate, and high-fat diets are used to modify drug seeking and reward, overlooking the notable capacity of these treatments to alter the gut microbiome. This review aims to stimulate research on substance abuse-gut microbiome interactions by illustrating how drugs of abuse share with antibiotics, sodium butyrate, and fat-laden diets the ability to modify the host microbial community.
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Affiliation(s)
- Mariana Angoa-Pérez
- Research and Development Service, John D. Dingell VA Medical Center, and Department of Psychiatry and Behavioral Neurosciences, Wayne State University School of Medicine, Detroit, Michigan
| | - Donald M Kuhn
- Research and Development Service, John D. Dingell VA Medical Center, and Department of Psychiatry and Behavioral Neurosciences, Wayne State University School of Medicine, Detroit, Michigan
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13
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Trotta RJ, Swanson KC. Prenatal and Postnatal Nutrition Influence Pancreatic and Intestinal Carbohydrase Activities of Ruminants. Animals (Basel) 2021; 11:171. [PMID: 33450809 PMCID: PMC7828265 DOI: 10.3390/ani11010171] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2020] [Revised: 01/04/2021] [Accepted: 01/10/2021] [Indexed: 11/17/2022] Open
Abstract
In ruminant livestock species, nutrition can play an important role in the long-term programming of gastrointestinal function. Pancreatic and small intestinal digestive enzymes are important for postruminal digestion of carbohydrates and protein. Carbohydrases have been shown to respond to changes in the level of feed intake and the dietary inclusion of specific nutrients, including arginine, butyrate, folic acid, fructose, and leucine. Understanding how diet influences enzyme development and activity during prenatal and postnatal life could lead to the development of dietary strategies to optimize offspring growth and development to increase digestive efficiency of ruminant livestock species. More research is needed to understand how changes in fetal or neonatal carbohydrase activities in response to nutrition influence long-term growth performance and efficiency in ruminant livestock species to optimize nutritional strategies.
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Affiliation(s)
- Ronald J. Trotta
- Department of Animal and Food Sciences, University of Kentucky, Lexington, KY 40546, USA;
| | - Kendall C. Swanson
- Department of Animal Sciences, North Dakota State University, Fargo, ND 58108, USA
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14
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Abstract
Pregastric fermentation along with production practices that are dependent on high-energy diets means ruminants rely heavily on starch and protein assimilation for a substantial portion of their nutrient needs. While the majority of dietary starch may be fermented in the rumen, significant portions can flow to the small intestine. The initial phase of small intestinal digestion requires pancreatic α-amylase. Numerous nutritional factors have been shown to influence pancreatic α-amylase secretion with starch producing negative effects and casein, certain amino acids and dietary energy having positive effects. To date, manipulation of α-amylase secretion has not resulted in substantial changes in digestibility. The second phase of digestion involves the actions of the brush border enzymes sucrase-isomaltase and maltase-glucoamylase. Genetically, ruminants appear to possess these enzymes; however, the absence of measurable sucrase activity and limited adaptation with changes in diet suggests a reduced capacity for this phase of digestion. The final phase of carbohydrate assimilation is glucose transport. Ruminants possess Na+-dependent glucose transport that has been shown to be inducible. Because of the nature of pregastric fermentation, ruminants see a near constant flow of microbial protein to the small intestine. This results in a nutrient supply, which places a high priority on protein digestion and utilization. Comparatively, little research has been conducted describing protein assimilation. Enzymes and processes appear consistent with non-ruminants and are likely not limiting for efficient digestion of most feedstuffs. The mechanisms regulating the nutritional modulation of digestive function in the small intestine are complex and coordinated via the substrate, neural and hormonal effects in the small intestine, pancreas, peripheral tissues and the pituitary-hypothalamic axis. More research is needed in ruminants to help unravel the complexities by which small intestinal digestion is regulated with the aim of developing approaches to enhance and improve the efficiency of small intestinal digestion.
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15
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Guo L, Tian H, Yao J, Ren H, Yin Q, Cao Y. Leucine improves α-amylase secretion through the general secretory signaling pathway in pancreatic acinar cells of dairy calves. Am J Physiol Cell Physiol 2020; 318:C1284-C1293. [PMID: 32320287 DOI: 10.1152/ajpcell.00396.2019] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2023]
Abstract
The present study aimed to elucidate the mechanisms by which leucine impacts the secretion of pancreatic enzymes, especially amylase, by studying the proteomics profiles of pancreatic acinar (PA) cells from dairy cows. PA cells, the experimental model, were treated with four concentrations of leucine (0, 0.23, 0.45, and 0.90 mM). The abundance of different proteins in the four leucine treatment groups was detected. Label-free proteomic analysis enabled the identification of 1,906 proteins in all four treatment groups, and 1,350 of these proteins showed common expression across the groups. The primary effects of leucine supplementation were increased (P < 0.05) citrate synthase and ATPase activity, which enlarged the cytosolic ATP pool, and the upregulation of secretory protein 61 (Sec61) expression, which promoted protein secretion. In summary, these results suggest that leucine increases citrate synthase in the TCA cycle and ATPase activity and promotes the Sec signaling pathway to increase the exocrine function of PA cells.
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Affiliation(s)
- Long Guo
- College of Animal Science and Technology, Northwest A&F University, Yangling, China.,State Key Laboratory of Grassland Agro-Ecosystems of Lanzhou University, Lanzhou, China.,College of Pastoral Agriculture Science and Technology, Lanzhou University, Lanzhou, China
| | - Huibin Tian
- College of Animal Science and Technology, Northwest A&F University, Yangling, China
| | - Junhu Yao
- College of Animal Science and Technology, Northwest A&F University, Yangling, China
| | - Hao Ren
- College of Animal Science and Technology, Northwest A&F University, Yangling, China
| | - Qinyan Yin
- College of Animal Science and Technology, Northwest A&F University, Yangling, China
| | - Yangchun Cao
- College of Animal Science and Technology, Northwest A&F University, Yangling, China
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16
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Trotta RJ, Sitorski LG, Acharya S, Brake DW, Swanson KC. Duodenal Infusions of Starch with Casein or Glutamic Acid Influence Pancreatic and Small Intestinal Carbohydrase Activities in Cattle. J Nutr 2020; 150:784-791. [PMID: 31875476 DOI: 10.1093/jn/nxz319] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2019] [Revised: 10/10/2019] [Accepted: 12/03/2019] [Indexed: 01/06/2023] Open
Abstract
BACKGROUND Small intestinal starch digestion in ruminants is potentially limited by inadequate production of carbohydrases. Previous research has demonstrated that small intestinal starch digestion can be improved by postruminal supply of casein or glutamic acid. However, the mechanisms by which casein and glutamic acid increase starch digestion are not well understood. OBJECTIVES The objective of this experiment was to evaluate the effects of duodenal infusions of starch with casein or glutamic acid on postruminal carbohydrase activities in cattle. METHODS Twenty-two steers [mean body weight (BW) = 179 ± 4.23 kg] were surgically fitted with duodenal and ileal cannulas and limit-fed a soybean hull-based diet containing small amounts of starch. Raw cornstarch (1.61 ± 0.0869 kg/d) was infused into the duodenum alone (control), or with 118 ± 7.21 g glutamic acid/d, or 428 ± 19.4 g casein/d. Treatments were infused continuously for 58 d and then steers were killed for tissue collection. Activities of pancreatic (α-amylase) and intestinal (maltase, isomaltase, glucoamylase, sucrase) carbohydrases were determined. Data were analyzed as a randomized complete block (replicate group) design using the GLM procedure of SAS to determine effects of infusion treatment. RESULTS Duodenal casein infusion increased (P < 0.05) pancreatic α-amylase activity by 290%. Duodenal glutamic acid infusion increased (P < 0.03) duodenal maltase activity by 233%. Duodenal casein infusion increased jejunal maltase (P = 0.02) and glucoamylase (P = 0.03) activity per gram protein by 62.9% and 97.4%, respectively. Duodenal casein infusion tended to increase (P = 0.10) isomaltase activity per gram jejunum by 38.5% in the jejunum. Sucrase activity was not detected in any segment of the small intestine. CONCLUSIONS These results suggest that small intestinal starch digestion can be improved in cattle with increased small intestinal flow of casein through increases in postruminal carbohydrase activities.
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Affiliation(s)
- Ronald J Trotta
- Department of Animal Sciences, North Dakota State University, Fargo, ND, USA
| | - Leonardo G Sitorski
- Department of Animal Sciences, North Dakota State University, Fargo, ND, USA
| | - Subash Acharya
- Department of Animal Science, South Dakota State University, Brookings, SD, USA
| | - Derek W Brake
- Department of Animal Science, South Dakota State University, Brookings, SD, USA
| | - Kendall C Swanson
- Department of Animal Sciences, North Dakota State University, Fargo, ND, USA
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17
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Trotta RJ, Vasquez-Hidalgo MA, Vonnahme KA, Swanson KC. Effects of Nutrient Restriction During Midgestation to Late Gestation on Maternal and Fetal Postruminal Carbohydrase Activities in Sheep. J Anim Sci 2020; 98:skz393. [PMID: 31879771 PMCID: PMC6986434 DOI: 10.1093/jas/skz393] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2019] [Accepted: 12/26/2019] [Indexed: 12/13/2022] Open
Abstract
To examine the effects of nutrient restriction during midgestation to late gestation on maternal and fetal digestive enzyme activities, 41 singleton ewes (48.3 ± 0.6 kg of BW) were randomly assigned to dietary treatments: 100% (control; CON; n = 20) or 60% of nutrient requirements (restricted; RES; n = 21) from day 50 until day 90 (midgestation). At day 90, 14 ewes (CON, n = 7; RES, n = 7) were euthanized. The remaining ewes were subjected to treatments of nutrient restriction or remained on a control diet from day 90 until day 130 (late gestation): CON-CON (n = 6), CON-RES (n = 7), RES-CON (n = 7), and RES-RES (n = 7) and were euthanized on day 130. The fetal and maternal pancreas and small intestines were weighed, subsampled, and assayed for digestive enzyme activity. One unit (U) of enzyme activity is equal to 1 µmol of product produced per minute for amylase, glucoamylase, lactase, and trypsin and 0.5 µmol of product produced per minute for maltase and isomaltase. Nutrient restriction during midgestation and late gestation decreased (P < 0.05) maternal pancreatic and small intestinal mass but did not affect fetal pancreatic or small intestinal mass. Maternal nutrient restriction during late gestation decreased (P = 0.03) fetal pancreatic trypsin content (U/pancreas) and tended to decrease (P < 0.08) fetal pancreatic trypsin concentration (U/g), specific activity (U/g protein), and content relative to BW (U/kg of BW). Nutrient restriction of gestating ewes decreased the total content of α-amylase (P = 0.04) and tended to decrease total content of trypsin (P = 0.06) and protein (P = 0.06) in the maternal pancreas on day 90. Nutrient restriction during midgestation on day 90 and during late gestation on day 130 decreased (P = 0.04) maternal pancreatic α-amylase-specific activity. Sucrase activity was undetected in the fetal and maternal small intestine. Nutrient restriction during late gestation increased (P = 0.01) maternal small intestinal maltase and lactase concentration and tended to increase (P = 0.06) isomaltase concentration. Realimentation during late gestation after nutrient restriction during midgestation increased lactase concentration (P = 0.04) and specific activity (P = 0.05) in the fetal small intestine. Fetal small intestinal maltase, isomaltase, and glucoamylase did not respond to maternal nutrient restriction. These data indicate that some maternal and fetal digestive enzyme activities may change in response to maternal nutrient restriction.
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Affiliation(s)
- Ronald J Trotta
- Department of Animal Sciences, North Dakota State University, Fargo, ND
| | | | | | - Kendall C Swanson
- Department of Animal Sciences, North Dakota State University, Fargo, ND
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18
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Leucine Regulates the Exocrine Function in Pancreatic Tissue of Dairy Goats In Vitro. BIOMED RESEARCH INTERNATIONAL 2019; 2019:7521715. [PMID: 31737677 PMCID: PMC6815606 DOI: 10.1155/2019/7521715] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/21/2019] [Revised: 08/23/2019] [Accepted: 09/14/2019] [Indexed: 12/18/2022]
Abstract
This study aimed to investigate the effects of leucine (Leu) on the synthesis and secretion of digestive enzymes in cultured pancreatic tissue of dairy goats and on the signaling molecules. Fresh pancreatic tissue from dairy goats was cut into approximately 2 mm × 2 mm pieces and incubated in oxygenated Krebs-Ringer bicarbonate buffer containing 0 (the control), 0.40, 0.80, or 1.60 mM Leu at 39°C in a CO2 incubator for 180 min. The results showed that Leu increased the release of α-amylase, trypsin, and chymotrypsin in the buffer and tissue, as well as the total activity (P < 0.05), especially at 0.40 and 0.80 mM. Compared with the control, 1.60 mM Leu increased the release of α-amylase and the total activity of trypsin and chymotrypsin (P < 0.05) but had no effect on the tissue concentration of α-amylase, trypsin, and chymotrypsin or the total activity of α-amylase (P > 0.05). Leu improved the mRNA expression of α-amylase, trypsin, and chymotrypsin (P < 0.05), especially at 0.80 and 1.60 mM. The activity and mRNA expression of lipase were not affected (P > 0.05). Compared with the control, 0.40 and 0.80 mM Leu increased the expression of the γ isoform of 4EBP1 (P < 0.05), implying increased phosphorylation of 4EBP1. Leu increased the phosphorylation of S6K1 (P < 0.05). Compared with the control, 0.40 and 0.80 mM Leu decreased the eEF2 phosphorylation level (P < 0.05). Conclusively, these results suggested that Leu could regulate the synthesis of pancreatic enzymes by increasing the mRNA expression and phosphorylation level of protein factors in the mammalian target of rapamycin pathway and the optimal Leu level in this experiment was 0.80 mM.
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Abstract
Some amino acids (AA) act through several signalling pathways and mechanisms to mediate the control of gene expression at the translation level, and the regulation occurs, specifically, on the initiation and the signalling pathways for translation. The translation of mRNA to protein synthesis proceeds through the steps of initiation and elongation, and AA act as important feed-forward activators that are involved in many pathways, such as the sensing and the transportation of AA by cells, in these steps in many tissues of mammals. For the translation, phosphorylation of eukaryotic translation initiation factor 2α (eIF2α) is a critical molecule that controls the translation initiation and its functions can be regulated by some AA. Another control point in the mRNA binding step in the translation initiation is at the regulation by mammalian target of rapamycin, which requires a change of phosphorylation status of ribosomal protein S6. In fact, the change of phosphorylation status of ribosomal protein S6 might be involved in global protein synthesis. The present review summarises recent work on the molecular mechanisms of the regulation of protein synthesis by AA and highlights new findings.
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20
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Effects of dietary leucine and phenylalanine on gastrointestinal development and small intestinal enzyme activities in milk-fed holstein dairy calves. Biosci Rep 2019; 39:BSR20181733. [PMID: 30563927 PMCID: PMC6350069 DOI: 10.1042/bsr20181733] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2018] [Revised: 12/12/2018] [Accepted: 12/17/2018] [Indexed: 01/24/2023] Open
Abstract
This study was investigated the effects of dietary supplementation of leucine and phenylalanine on the development of the gastrointestinal tract and the intestinal digestive enzyme activity in male Holstein dairy calves. Twenty calves with a body weight of 38 ± 3 kg at 1 day of age were randomly divided into four groups: a control group, a leucine group (1.435 g·l−1), a phenylalanine group (0.725 g·l−1), and a mixed amino acid group (1.435 g·l−1 leucine plus 0.725 g·l−1 phenylalanine). The supplementation of leucine decreased the short-circuit current (Isc) of the rumen and duodenum (P<0.01); phenylalanine did not show any influence on the Isc of rumen and duodenum (P>0.05), and also counteracted the Isc reduction caused by leucine. Leucine increased the trypsin activity at the 20% relative site of the small intestine (P<0.05). There was no difference in the activity of α-amylase and of lactase in the small intestinal chyme among four treatments (P>0.05). The trypsin activity in the anterior segment of the small intestine was higher than other segments, whereas the α-amylase activity in the posterior segment of the small intestine was higher than other segments. Leucine can reduce Isc of the rumen and duodenum, improve the development of the gastrointestinal tract, and enhance trypsin activity; phenylalanine could inhibit the effect of leucine in promoting intestinal development.
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21
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Inhibitory effect of high leucine concentration on α-amylase secretion by pancreatic acinar cells: possible key factor of proteasome. Biosci Rep 2018; 38:BSR20181455. [PMID: 30361293 PMCID: PMC6294628 DOI: 10.1042/bsr20181455] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2018] [Revised: 10/17/2018] [Accepted: 10/23/2018] [Indexed: 01/13/2023] Open
Abstract
The present study aimed to investigate whether leucine affects the pancreatic exocrine by controlling the antisecretory factor (AF) and cholecystokinin receptor (CCKR) expression as well as the proteasome activity in pancreatic acinar cells of dairy calves. The pancreatic acinar cells were isolated from newborn Holstein bull calves and cultured using the Dulbecco’s modified Eagle’s medium/nutrient mixture F12 Ham’s liquid (DMEM/F12). There were six treatments of leucine dosage including 0 (control), 0.23, 0.45, 1.35, 4.05, and 12.15 mM, respectively. After culture for 3 h, the samples were collected for subsequent analysis. As the leucine concentration increased from 0 to 1.35 mM, the α-amylase activity in media decreased significantly (P<0.05), while further increase in leucine concentration did not show any decrease in α-amylase activity. Addition of leucine inhibited (P<0.05) the expression of AF and CCKR, and decreased the activity of proteasome (P<0.05) by 76%, 63%, 24%, 7%, and 9%, respectively. Correlation analysis results showed α-amylase secretion was negatively correlated with leucine concentration (P<0.01), and positively correlated with proteasome activity (P<0.01) and the expression of CCK1R (P<0.01) and AF (P<0.05). The biggest regression coefficient was showed between α-amylase activity and proteasome (0.7699, P<0.001). After inhibition of proteasome by MG-132, low dosage leucine decreased (P<0.05) the activity of proteasome and α-amylase, as well as the expression of CCK1R. In conclusion, we demonstrated that the high-concentration leucine induced decrease in α-amylase release was mainly by decreasing proteasome activity.
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Guo L, Liang Z, Zheng C, Liu B, Yin Q, Cao Y, Yao J. Leucine Affects α-Amylase Synthesis through PI3K/Akt-mTOR Signaling Pathways in Pancreatic Acinar Cells of Dairy Calves. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2018; 66:5149-5156. [PMID: 29733580 DOI: 10.1021/acs.jafc.8b01111] [Citation(s) in RCA: 31] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/08/2023]
Abstract
Dietary nutrient utilization, particularly starch, is potentially limited by digestion in dairy cow small intestine because of shortage of α-amylase. Leucine acts as an effective signal molecular in the mTOR signaling pathway, which regulates a series of biological processes, especially protein synthesis. It has been reported that leucine could affect α-amylase synthesis and secretion in ruminant pancreas, but mechanisms have not been elaborated. In this study, pancreatic acinar (PA) cells were used as a model to determine the cellular signal of leucine influence on α-amylase synthesis. PA cells were isolated from newborn Holstein dairy bull calves and cultured in Dulbecco's modifed Eagle's medium/nutrient mixture F12 liquid media containing four leucine treatments (0, 0.23, 0.45, and 0.90 mM, respectively), following α-amylase activity, zymogen granule, and signal pathway factor expression detection. Rapamycin, a specific inhibitor of mTOR, was also applied to PA cells. Results showed that leucine increased ( p < 0.05) synthesis of α-amylase as well as phosphorylation of PI3K, Akt, mTOR, and S6K1 while reduced ( p < 0.05) GCN2 expression. Inhibition of mTOR signaling downregulated the α-amylase synthesis. In addition, the extracellular leucine dosage significantly influenced intracellular metabolism of isoleucine ( p < 0.05). Overall, leucine regulates α-amylase synthesis through promoting the PI3K/Akt-mTOR pathway and reducing the GCN2 pathway in PA cells of dairy calves. These pathways form the signaling network that controls the protein synthesis and metabolism. It would be of great interest in future studies to explore the function of leucine in ruminant nutrition.
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Affiliation(s)
- Long Guo
- College of Animal Science and Technology , Northwest A&F University , Yangling , Shaanxi 712100 , People's Republic of China
| | - Ziqi Liang
- College of Animal Science and Technology , Northwest A&F University , Yangling , Shaanxi 712100 , People's Republic of China
| | - Chen Zheng
- College of Animal Science and Technology , Northwest A&F University , Yangling , Shaanxi 712100 , People's Republic of China
| | - Baolong Liu
- College of Animal Science and Technology , Northwest A&F University , Yangling , Shaanxi 712100 , People's Republic of China
| | - Qingyan Yin
- College of Animal Science and Technology , Northwest A&F University , Yangling , Shaanxi 712100 , People's Republic of China
| | - Yangchun Cao
- College of Animal Science and Technology , Northwest A&F University , Yangling , Shaanxi 712100 , People's Republic of China
| | - Junhu Yao
- College of Animal Science and Technology , Northwest A&F University , Yangling , Shaanxi 712100 , People's Republic of China
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