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Garavito-Duarte YR, Levesque CL, Herrick K, Perez-Palencia JY. A corn-fermented protein ingredient can be included in early nursey diets without compromising pig growth performance and health status. Transl Anim Sci 2024; 8:txad149. [PMID: 38390272 PMCID: PMC10883705 DOI: 10.1093/tas/txad149] [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: 09/23/2023] [Accepted: 01/04/2024] [Indexed: 02/24/2024] Open
Abstract
In nursery diets, ingredients with high protein content and highly digestible nutrients, such as corn-fermented protein product with added yeast mass (GDDY), can be included as an alternative to common protein sources. This study investigated the dietary inclusion of GDDY as an alternative protein source on growth performance and intestinal health of weaned pigs. A total of 594 weaned pigs (5.7 ± 0.9 kg; 18.5 days of age) were allotted to 36 pens in a randomized incomplete block design. Pens were assigned to one of 4 dietary treatments: CON: a common nursery feeding program; SBM75: CON diet replacing 75% of soybean meal (SBM) with GDDY; FM/ESBM: CON diet without fish meal (FM) and enzyme-treated SBM (ESBM) + GDDY; GDDY50: CON diet replacing 50% of SBM, FM, and ESBM with GDDY. Experimental diets were formulated to meet nutrient requirements of nursery pigs and provided in meal form through four phases during the nursery period. Pig growth performance was assessed on days 7, 14, 21, 28, 42, and 53. Pen fecal score was assessed daily from days 0 to 14, and 3 times per week from days 15 to 35. Intestinal health was assessed based on plasma immunoglobulin A (IgA) concentration and the differential sugar absorption test. The total tract digestibility of dry matter (DM), crude protein (CP), gross energy (GE), and phosphorus was also evaluated. From days 0 to 7 and days 7 to 14, dietary treatment had no effect (P > 0.05) on BW, ADG, and ADFI. For the rest of the experimental period, ADG and ADFI were greater (P < 0.05) in pigs fed CON in comparison with those fed SBM75 and GDDY50 and did not differ from pigs fed FM/ESBM. Pigs fed GDDY50 tended (P = 0.082) to have greater serum IgA concentration on day 20 when compared with SBM75 and FM/ESBM pigs. There were no differences among dietary treatments for DM, CP, and GE digestibility. Phosphorus digestibility was higher in FM/ESBM (P < 0.05) compared with SBM75 and GDDY50. These results supported the hypothesis that GDDY can be incorporated in nursery pig diets during the first couple weeks after weaning without affecting growth performance. However, in the late nursery period, inclusion levels starting at 14% can compromise performance.
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Affiliation(s)
- Yesid R Garavito-Duarte
- Department of Animal Science, South Dakota State University, Brookings, SD 57007, USA
- Department of Animal Science, North Carolina State University, Raleigh, NC 27695, USA
| | - Crystal L Levesque
- Department of Animal Science, South Dakota State University, Brookings, SD 57007, USA
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Ma TF, Huang JN, Wen B, Gao JZ, Chen ZZ. Genome-wide identification and expression analysis of C-type lectins in discus fish (Symphysodon aequifasciatus) during parental care. FISH & SHELLFISH IMMUNOLOGY 2024; 144:109291. [PMID: 38104702 DOI: 10.1016/j.fsi.2023.109291] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/04/2023] [Revised: 12/07/2023] [Accepted: 12/09/2023] [Indexed: 12/19/2023]
Abstract
Discus fish (Symphysodon aequifasciatus) exhibit a unique parental care behavior: adult discus produces secretion through their skin, on which the larvae live after birth. The immune components in the skin mucus of parental discus would change during different parental care. C-type lectins (CTLs) could identify and eliminate pathogenic microorganisms and play important roles in innate immunity. Studies on CTLs of discus fish especially during parental care, however, are scarce. Here, we identified 186 CTL genes that distributed in 27 linkage groups based on discus genome. Phylogenetic analysis showed that S. aequifasciatus CTL (SaCTL) members were grouped into 14 subfamilies. A total of 80 gene replication events occurred, of which 15 pairs were subjected to segmental duplication and 65 pairs underwent tandem duplication. Ka/Ks ranged from 0.11 (SaCTL25/SaCTL158) to 0.68 (SaCTL36/SaCTL69), all undergoing purifying selection. RNA-seq analysis revealed that SaCTL members, including duplicated genes, in the skin of parental discus show distinct expression patterns in different care stages and between male and female parents. The SaCTL11 was differentially expressed in most care stages and reached the maximum after eggs spawned, but the expression of its paired SaCTL14 was low in each stage. The SaCTL39 increased first and then decreased, reaching a peak in eggs spawned, while paired SaCTL48 first decreased and then increased, reaching a peak in hatched eggs. The SaCTL50 was differentially expressed only in female fish during care, but not in male fish. These results provide new insights into the evolution and potential functional differentiation of CTLs in discus fish during parental care.
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Affiliation(s)
- Teng-Fei Ma
- Key Laboratory of Freshwater Aquatic Genetic Resources, Ministry of Agriculture and Rural Affairs, Shanghai Ocean University, Shanghai, 201306, China; Key Laboratory of Exploration and Utilization of Aquatic Genetic Resources, Ministry of Education, Shanghai Ocean University, Shanghai, 201306, China
| | - Jun-Nan Huang
- Key Laboratory of Freshwater Aquatic Genetic Resources, Ministry of Agriculture and Rural Affairs, Shanghai Ocean University, Shanghai, 201306, China; Key Laboratory of Exploration and Utilization of Aquatic Genetic Resources, Ministry of Education, Shanghai Ocean University, Shanghai, 201306, China
| | - Bin Wen
- Key Laboratory of Freshwater Aquatic Genetic Resources, Ministry of Agriculture and Rural Affairs, Shanghai Ocean University, Shanghai, 201306, China; Key Laboratory of Exploration and Utilization of Aquatic Genetic Resources, Ministry of Education, Shanghai Ocean University, Shanghai, 201306, China; National Demonstration Center for Experimental Fisheries Science Education, Shanghai Ocean University, Shanghai, 201306, China.
| | - Jian-Zhong Gao
- Key Laboratory of Freshwater Aquatic Genetic Resources, Ministry of Agriculture and Rural Affairs, Shanghai Ocean University, Shanghai, 201306, China; Key Laboratory of Exploration and Utilization of Aquatic Genetic Resources, Ministry of Education, Shanghai Ocean University, Shanghai, 201306, China; National Demonstration Center for Experimental Fisheries Science Education, Shanghai Ocean University, Shanghai, 201306, China
| | - Zai-Zhong Chen
- Key Laboratory of Freshwater Aquatic Genetic Resources, Ministry of Agriculture and Rural Affairs, Shanghai Ocean University, Shanghai, 201306, China; Key Laboratory of Exploration and Utilization of Aquatic Genetic Resources, Ministry of Education, Shanghai Ocean University, Shanghai, 201306, China; National Demonstration Center for Experimental Fisheries Science Education, Shanghai Ocean University, Shanghai, 201306, China.
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Kosmerl E, Martínez-Sánchez V, Calvo MV, Jiménez-Flores R, Fontecha J, Pérez-Gálvez A. Food matrix impacts bioaccessibility and assimilation of acid whey-derived milk fat globule membrane lipids in Caco-2 cells. Front Nutr 2023; 10:1177152. [PMID: 37229475 PMCID: PMC10203207 DOI: 10.3389/fnut.2023.1177152] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2023] [Accepted: 04/18/2023] [Indexed: 05/27/2023] Open
Abstract
The milk fat globule membrane (MFGM) imparts human health benefits ranging from improved immune system, gut, and brain function to improved cardiometabolic health. The industry's growing interest in introducing MFGM-enriched foods requires scientific evidence that the benefits derived from this compound are not affected by the formulation or processes that may alter its function, such as the digestion process. In this study, the impact of food matrices and supplementation levels on the bioaccessibility and assimilation of MFGM lipids in cell culture was investigated. Three food matrices including a protein-rich jelly, carbohydrate-rich cookie, and a carbohydrate- and fat-rich cookie with sunflower oil (SF-cookie) were supplemented with an MFGM ingredient derived from cottage cheese acid whey at 2, 5, and 10% (w/w). Each formulation underwent simulated digestion consisting of oral, gastric, and intestinal phases, and the micellar fraction was collected for both analysis and lipid assimilation in Caco-2 intestinal cells. The micellar fractions were diluted and applied to the cells for 4 h. A lipidomic approach was used to assess the lipid profiles of micellar fractions and intestinal cells. The micelles from digested jellies, cookies, and SF-cookies containing MFGM showed a distinct separation using partial least squares discriminant analysis (PLS-DA). Both correlation loadings and variable importance in projection (VIP) scores demonstrated a tendency of MFGM polar lipids (ceramides, glucosylceramides) for micelles from digested jelly, whereas micelles from digested cookies were associated with MFGM neutral lipids (free fatty acids, cholesterol, etc.). The effect of supplementation level on the micellar lipid profiles reinforced this pattern. The lipid profiles of intestinal cells after incubation with the micellar fractions differed considerably from the corresponding micellar lipid profiles. Specifically, the SF-cookie-treated cells were associated with a greater abundance of PUFA relative to jelly- and cookie-treated cells; however, increasing MFGM supplementation showed irregular patterns and rearrangement of cellular lipid profiles, suggesting the cells' role in regulating lipid metabolism in response to nutritional stimuli. The nature of lipid micellarization and assimilation in intestinal cells from MFGM-containing food formulations echoes the complexity of lipids inherent to the MFGM itself, suggesting the need for application-based MFGM supplementation.
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Affiliation(s)
- Erica Kosmerl
- Department of Food Science and Technology, The Ohio State University, Columbus, OH, United States
| | - Victoria Martínez-Sánchez
- Group of Chemistry and Biochemistry of Pigments, Instituto de la Grasa (CSIC), Sevilla, Spain
- Food Lipid Biomarkers and Health Group, Institute of Food Science Research (CSIC-UAM), Madrid, Spain
| | - María V. Calvo
- Food Lipid Biomarkers and Health Group, Institute of Food Science Research (CSIC-UAM), Madrid, Spain
| | - Rafael Jiménez-Flores
- Department of Food Science and Technology, The Ohio State University, Columbus, OH, United States
| | - Javier Fontecha
- Food Lipid Biomarkers and Health Group, Institute of Food Science Research (CSIC-UAM), Madrid, Spain
| | - Antonio Pérez-Gálvez
- Group of Chemistry and Biochemistry of Pigments, Instituto de la Grasa (CSIC), Sevilla, Spain
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Brun A, Magallanes ME, Karasov WH, Caviedes-Vidal E. Rapid and parallel changes in activity and mRNA of intestinal peptidase to match altered dietary protein levels in juvenile house sparrows ( Passer domesticus). J Exp Biol 2021; 224:jeb234708. [PMID: 33288529 DOI: 10.1242/jeb.234708] [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: 08/05/2020] [Accepted: 11/16/2020] [Indexed: 11/20/2022]
Abstract
Although dietary flexibility in digestive enzyme activity (i.e. reaction rate) is widespread in vertebrates, mechanisms are poorly understood. When laboratory rats are switched to a higher protein diet, the activities of apical intestinal peptidases increase within 15 h, in some cases by rapid increase in enzyme transcription followed by rapid translation and translocation to the intestine's apical, brush-border membrane (BBM). Focusing on aminopeptidase-N (APN), we studied intestinal digestive enzyme flexibility in birds, relying on activity and mRNA data from the same animals. Our model was nestling house sparrows (Passer domesticus), already known to modulate intestinal peptidase activity when switching between lower and higher protein diets. Twenty-four hours after a switch from an adequate, lower protein diet to a higher protein diet, APN activity was increased in both whole intestinal tissue homogenates and in isolated BBM, but not at 12 h post-diet switch. Twenty-four hours after a reverse switch back to the lower protein diet, APN activity was decreased, but not at 12 h post-diet switch. Changes in APN activity in both diet switch experiments were associated with parallel changes in APN mRNA. Although transcriptional changes seem to be an important mechanism underlying dietary modulation of intestinal peptidase in both nestling house sparrows and laboratory rodents, the time course for modulation in nestlings seemed slower (taking approximately twice as long) compared with laboratory rodents. It may be ecologically advantageous if nestlings biochemically restructure their gut in response to a sustained increase in insects and protein intake rather than one or a few lucky insect meals.
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Affiliation(s)
- Antonio Brun
- University of Wisconsin-Madison, Department of Forest and Wildlife Ecology, Madison, WI 53706, USA
- Consejo Nacional de Investigaciones Científicas y Técnicas, Instituto Multidisciplinario de Investigaciones Biológicas de San Luis, 5700 San Luis, Argentina
- Universidad Nacional de San Luis, Facultad de Ciencias de la Salud, 5700 San Luis, Argentina
| | - Melisa E Magallanes
- Consejo Nacional de Investigaciones Científicas y Técnicas, Instituto Multidisciplinario de Investigaciones Biológicas de San Luis, 5700 San Luis, Argentina
| | - William H Karasov
- University of Wisconsin-Madison, Department of Forest and Wildlife Ecology, Madison, WI 53706, USA
| | - Enrique Caviedes-Vidal
- University of Wisconsin-Madison, Department of Forest and Wildlife Ecology, Madison, WI 53706, USA
- Consejo Nacional de Investigaciones Científicas y Técnicas, Instituto Multidisciplinario de Investigaciones Biológicas de San Luis, 5700 San Luis, Argentina
- Universidad Nacional de San Luis, Departamento de Biología, 5700 San Luis, Argentina
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Hasan MS, Feugang JM, Liao SF. A Nutrigenomics Approach Using RNA Sequencing Technology to Study Nutrient-Gene Interactions in Agricultural Animals. Curr Dev Nutr 2019; 3:nzz082. [PMID: 31414073 PMCID: PMC6686084 DOI: 10.1093/cdn/nzz082] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2019] [Revised: 06/08/2019] [Accepted: 07/08/2019] [Indexed: 11/15/2022] Open
Abstract
Thorough understanding of animal gene expression driven by dietary nutrients can be regarded as a bottom line of advanced animal nutrition research. Nutrigenomics (including transcriptomics) studies the effects of dietary nutrients on cellular gene expression and, ultimately, phenotypic changes in living organisms. Transcriptomics can be applied to investigate animal tissue transcriptomes at a defined nutritional state, which can provide a holistic view of intracellular RNA expression. As a novel transcriptomics approach, RNA sequencing (RNA-Seq) technology can monitor all gene expressions simultaneously in response to dietary intervention. The principle and history of RNA-Seq are briefly reviewed, and its 3 principal steps are described in this article. Application of RNA-Seq in different areas of animal nutrition research is summarized. Lastly, the application of RNA-Seq in swine science and nutrition is also reviewed. In short, RNA-Seq holds significant potential to be employed for better understanding the nutrient-gene interactions in agricultural animals.
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Affiliation(s)
- M Shamimul Hasan
- Department of Animal and Dairy Sciences, Mississippi State University, Mississippi State, MS, USA
| | - Jean M Feugang
- Department of Animal and Dairy Sciences, Mississippi State University, Mississippi State, MS, USA
| | - Shengfa F Liao
- Department of Animal and Dairy Sciences, Mississippi State University, Mississippi State, MS, USA
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Lima GC, Vieira VCC, Cazarin CBB, Ribeiro RDR, Junior SB, de Albuquerque CL, Vidal RO, Netto CC, Yamada ÁT, Augusto F, Maróstica Junior MR. Fructooligosaccharide intake promotes epigenetic changes in the intestinal mucosa in growing and ageing rats. Eur J Nutr 2017; 57:1499-1510. [PMID: 28324207 DOI: 10.1007/s00394-017-1435-x] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2016] [Accepted: 03/06/2017] [Indexed: 01/16/2023]
Abstract
PURPOSE The aim of this study was to investigate the relationship between fructooligosaccharide (FOS) intake at different life stages of Wistar rats and its stimulatory effects on intestinal parameters. METHODS Recently weaned and ageing female rats were divided into growing and ageing treatments, which were fed diets that partially replaced sucrose with FOS for 12 weeks. RESULTS Dietary FOS intake induced a significant increase in the numbers of Bifidobacterium and Lactobacillus in growing rats. FOS intake was associated with increased butyric acid levels and a reduced pH of the caecal contents at both ages. Differential gene expression patterns were observed by microarray analysis of growing and ageing animals fed the FOS diet. A total of 133 genes showed detectable changes in expression in the growing rats, while there were only 19 gene expression changes in ageing rats fed with FOS. CONCLUSION These results suggest that dietary FOS intake may be beneficial for some parameters of intestinal health in growing rats.
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Affiliation(s)
| | | | | | | | | | | | - Ramon Oliveira Vidal
- Sainte-Justine University Hospital Center, Université de Montreal, Montreal, Canada
| | - Claudia Cardoso Netto
- Department of Biochemistry, Biological Sciences and Health Center, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
| | | | - Fabio Augusto
- Institute of Chemistry, University of Campinas, Campinas, São Paulo, Brazil
| | - Mário Roberto Maróstica Junior
- School of Food Engineering, University of Campinas, Campinas, São Paulo, Brazil. .,Laboratório de Nutrição e Metabolismo-Departamento de Alimentos e Nutrição, Faculdade de Engenharia de Alimentos, Universidade Estadual de Campinas, R. Monteiro Lobato 80, Campinas, SP, 13083-862, Brazil.
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Qin C, Qiu K, Sun W, Jiao N, Zhang X, Che L, Zhao H, Shen H, Yin J. A proteomic adaptation of small intestinal mucosa in response to dietary protein limitation. Sci Rep 2016; 6:36888. [PMID: 27841298 PMCID: PMC5107940 DOI: 10.1038/srep36888] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2016] [Accepted: 10/21/2016] [Indexed: 12/14/2022] Open
Abstract
Dietary protein limitation (PL) is not only beneficial to human health but also applied to minimize nitrogen excretion in livestock production. However, the impact of PL on intestinal physiology is largely unknown. In this study, we identified 5275 quantitative proteins using a porcine model in which pigs suffered PL. A total of 202 proteins |log2 fold-change| > 1 were taken as differentially expressed proteins and subjected to functional and pathway enrichment analysis to reveal proteomic alterations of the jejunal mucosa. Combining with the results of western blotting analysis, we found that protein/carbohydrate digestion, intestinal mucosal tight junction and cell adhesion molecules, and the immune response to foreign antigens were increased in the jejunal mucosa of the pigs upon PL. In contrast, amino acid transport, innate and auto immunity, as well as cell proliferation and apoptosis were reduced. In addition, the expression of functional proteins that involved in DNA replication, transcription and mRNA splicing as well as translation were altered in the jejunal mucosa in response to PL. Furthermore, PL may reduce amino acid transport and cell proliferation through the depression of mTOR pathway. This study provides new insights into the molecular mechanisms underlying the small intestinal response to PL.
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Affiliation(s)
- Chunfu Qin
- State Key Lab of Animal Nutrition, College of Animal Science and Technology, China Agricultural University, Beijing, 100193, P. R. China
| | - Kai Qiu
- State Key Lab of Animal Nutrition, College of Animal Science and Technology, China Agricultural University, Beijing, 100193, P. R. China
| | - Wenjuan Sun
- State Key Lab of Animal Nutrition, College of Animal Science and Technology, China Agricultural University, Beijing, 100193, P. R. China
| | - Ning Jiao
- State Key Lab of Animal Nutrition, College of Animal Science and Technology, China Agricultural University, Beijing, 100193, P. R. China
| | - Xin Zhang
- State Key Lab of Animal Nutrition, College of Animal Science and Technology, China Agricultural University, Beijing, 100193, P. R. China
| | - Lianqiang Che
- Institute of Animal Nutrition, Sichuan Agricultural University, Ya'an, 625099, P. R. China
| | - Haiyi Zhao
- Genecreate Biological Engineering Co., Ltd., National Bio-industry Base, Wuhan, 430075, P. R. China
| | - Hexiao Shen
- Genecreate Biological Engineering Co., Ltd., National Bio-industry Base, Wuhan, 430075, P. R. China
| | - Jingdong Yin
- State Key Lab of Animal Nutrition, College of Animal Science and Technology, China Agricultural University, Beijing, 100193, P. R. China
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8
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Gui H, Shen Z. Concentrate diet modulation of ruminal genes involved in cell proliferation and apoptosis is related to combined effects of short-chain fatty acid and pH in rumen of goats. J Dairy Sci 2016; 99:6627-6638. [PMID: 27236768 DOI: 10.3168/jds.2015-10446] [Citation(s) in RCA: 32] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2015] [Accepted: 03/28/2016] [Indexed: 01/20/2023]
Abstract
Short-chain fatty acids (SCFA) regulate cell proliferation and cell apoptosis in gastrointestinal tissue in vitro and in vivo. We have tested the hypothesis that a medium-concentrate intake induces mRNA abundance alterations of genes involved in cell proliferation and cell apoptosis in the rumen epithelium of goats, and that these changes in mRNA abundance are related to ruminal SCFA concentration and ruminal pH. Goats (n=16) were randomly allocated to 2 groups and fed either a low-concentrate (LC) diet (10% concentrate; n=8) or a medium-concentrate (MC) diet (35% concentrate; n=8) in 2 equal portions daily. The individually housed goats were fed separately with their respective diet for 3wk and were slaughtered 6h after the morning feed on d 22. In vivo, goats receiving the MC treatment exhibited a greater ruminal SCFA concentration (73.7mM) compared with those receiving the LC treatment (53.2mM), and the pH decreased from 6.9 to 6.5. The expression of proliferative genes of cyclin A, cyclin B1, cyclin D1, cyclin E1, CDK1, CDK2, CDK4, and CDK6 mRNA in the MC group was enhanced. The gene expression of apoptosis genes (caspase 3, caspase 8, caspase 9, p53, and Bax) was significantly higher, and the ratio of Bcl-2 to Bax (Bcl-2/Bax) expression was lower in the MC group than in the LC group. The same trend was observed in the population of apoptotic cells analyzed by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling assay. The cell density in the stratum germinativum of the MC group was significantly increased compared with that in the LC group. During primary culture of rumen epithelial cells, SCFA or pH treatment alone of the culture medium had significant effects on the expression of most of the genes tested in the present study. Furthermore, SCFA and pH exerted combined effects on the expression of cyclin A, cyclin B1, cyclin E1, CDK6, p53, Bcl-2, and Bcl-2/Bax. Thus, the MC diet induces alteration of gene expression of the genes that regulate both cell proliferation and apoptosis. These genes are regulated by combined effect of ruminal SCFA and ruminal pH.
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Affiliation(s)
- Hongbing Gui
- Laboratory of Animal Physiology and Biochemistry, Nanjing Agriculture University, Nanjing, China, 210095
| | - Zanming Shen
- Laboratory of Animal Physiology and Biochemistry, Nanjing Agriculture University, Nanjing, China, 210095.
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Seeley RJ, Chambers AP, Sandoval DA. The role of gut adaptation in the potent effects of multiple bariatric surgeries on obesity and diabetes. Cell Metab 2015; 21:369-78. [PMID: 25662404 PMCID: PMC4351155 DOI: 10.1016/j.cmet.2015.01.001] [Citation(s) in RCA: 155] [Impact Index Per Article: 15.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Bariatric surgical procedures such as vertical sleeve gastrectomy (VSG) and Roux-en-Y gastric bypass (RYGB) are the most potent treatments available to produce sustained reductions in body weight and improvements in glucose regulation. While traditionally these effects are attributed to mechanical aspects of these procedures, such as restriction and malabsorption, a growing body of evidence from mouse models of these procedures points to physiological changes that mediate the potent effects of these surgeries. In particular, there are similar changes in gut hormone secretion, bile acid levels, and composition after both of these procedures. Moreover, loss of function of the nuclear bile acid receptor (FXR) greatly diminishes the effects of VSG. Both VSG and RYGB are linked to profound changes in the gut microbiome that also mediate at least some of these surgical effects. We hypothesize that surgical rearrangement of the gastrointestinal tract results in enteroplasticity caused by the high rate of nutrient presentation and altered pH in the small intestine that contribute to these physiological effects. Identifying the molecular underpinnings of these procedures provides new opportunities to understand the relationship of the gastrointestinal tract to obesity and diabetes as well as new therapeutic strategies to harness the effectiveness of surgery with less-invasive approaches.
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Affiliation(s)
- Randy J Seeley
- Departments of Surgery and Medicine, University of Michigan, Ann Arbor, MI 48109, USA.
| | - Adam P Chambers
- Department of Diabetes Pharmacology, Novo Nordisk, Copenhagen 2760 MÅLØV, Denmark
| | - Darleen A Sandoval
- Departments of Surgery and Medicine, University of Michigan, Ann Arbor, MI 48109, USA
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Lu Z, Gui H, Yao L, Yan L, Martens H, Aschenbach JR, Shen Z. Short-chain fatty acids and acidic pH upregulate UT-B, GPR41, and GPR4 in rumen epithelial cells of goats. Am J Physiol Regul Integr Comp Physiol 2015; 308:R283-93. [PMID: 25519731 DOI: 10.1152/ajpregu.00323.2014] [Citation(s) in RCA: 41] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Abstract
Currently, the mechanism(s) responsible for the regulation of urea transporter B (UT-B) expression levels in the epithelium of the rumen remain unclear. We hypothesized that rumen fermentation products affect ruminal UT-B expression. Therefore, the effects of short-chain fatty acids (SCFA), pH, ammonia, and urea on mRNA and protein levels of UT-B were assayed in primary rumen epithelial cell cultures and in rumen epithelium obtained from intact goats. In vitro, SCFA and acidic pH were found to synergetically stimulate both mRNA and protein expression of UT-B, whereas NH4Cl decreased mRNA and protein levels of UT-B at pH 6.8. Treatment with urea increased both levels at pH 7.4. When goats received a diet rich in nitrogen (N) and nonfiber carbohydrates (NFC), their rumen epithelium had higher levels of UT-B, and the rumen contained higher concentrations of SCFA and NH3-N with a lower pH. An increase in plasma urea-N concentration was also observed compared with the plasma of the goats that received a diet low in N and NFC. In a second feeding trial, goats that received a NFC-rich, but isonitrogenous, diet had higher mRNA and protein levels of UT-B, and higher levels of G protein-coupled receptor (GPR) 41 and GPR4, in their rumen epithelium. The ruminal concentrations of SCFA and NH3-N also increased, while a lower pH was detected. In contrast, the serum urea-N concentrations remained unchanged. These data indicate that ruminal SCFA and pH are key factors, via GPR4 and GPR41, in the dietary regulation of UT-B expression, and they have priority over changes in plasma urea.
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Affiliation(s)
- Zhongyan Lu
- Institute of Veterinary Physiology, Free University of Berlin, Berlin, Germany; and
| | - Hongbing Gui
- Laboratory of Animal Physiology and Biochemistry, Nanjing Agricultural University, Nanjing, China
| | - Lei Yao
- Laboratory of Animal Physiology and Biochemistry, Nanjing Agricultural University, Nanjing, China
| | - Lei Yan
- Laboratory of Animal Physiology and Biochemistry, Nanjing Agricultural University, Nanjing, China
| | - Holger Martens
- Institute of Veterinary Physiology, Free University of Berlin, Berlin, Germany; and
| | - Jörg R Aschenbach
- Institute of Veterinary Physiology, Free University of Berlin, Berlin, Germany; and
| | - Zanming Shen
- Laboratory of Animal Physiology and Biochemistry, Nanjing Agricultural University, Nanjing, China
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11
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Durber J, Otley A. Complementary and alternative medicine in inflammatory bowel disease: keeping an open mind. Expert Rev Clin Immunol 2014; 1:277-92. [DOI: 10.1586/1744666x.1.2.277] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/15/2023]
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12
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Sontag TJ, Chellan B, Getz GS, Reardon CA. Differing rates of cholesterol absorption among inbred mouse strains yield differing levels of HDL-cholesterol. J Lipid Res 2013; 54:2515-24. [PMID: 23812556 DOI: 10.1194/jlr.m040055] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
Inbred strains of mice with differing susceptibilities to atherosclerosis possess widely varying plasma HDL levels. Cholesterol absorption and lipoprotein formation were compared between atherosclerosis-susceptible, low-HDL C57BL6/J mice and atherosclerosis-resistant, high-HDL FVBN/J mice. [(3)H]cholesterol and triglyceride appeared in the plasma of FVB mice gavaged with cholesterol in olive oil at a much higher rate than in C57 mice. The plasma cholesterol was found almost entirely as HDL-cholesterol in both strains. Inhibition of lipoprotein catabolism with Tyloxapol revealed that the difference in the rate of [(3)H]cholesterol appearance in the plasma was due entirely to a greater rate of chylomicron secretion from the intestine of the FVB mice. Lipid absorption into the 2nd quarter of the small intestine is greater in the FVB mice and indicates that this region may contain the factors that give rise to the differences in absorption observed between the two mouse strains. Additionally, ad libitum feeding prior to cholesterol gavage accentuates the absorption rate differences compared with fasting. The resultant remodeling of the increased levels of chylomicron in the plasma may contribute to increased plasma HDL. Intestinal gene expression analysis reveals several genes that may play a role in these differences, including microsomal triglyceride transfer protein and ABCG8.
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Affiliation(s)
- Timothy J Sontag
- Department of Pathology, University of Chicago, Chicago, IL, USA.
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13
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Effect of fasting on the structure and function of the gastrointestinal tract of house sparrows (Passer domesticus). Comp Biochem Physiol A Mol Integr Physiol 2012; 163:103-10. [DOI: 10.1016/j.cbpa.2012.05.189] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/29/2012] [Revised: 05/11/2012] [Accepted: 05/14/2012] [Indexed: 11/21/2022]
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14
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Ndiaye F, Vuong T, Duarte J, Aluko RE, Matar C. Anti-oxidant, anti-inflammatory and immunomodulating properties of an enzymatic protein hydrolysate from yellow field pea seeds. Eur J Nutr 2012; 51:29-37. [PMID: 21442413 DOI: 10.1007/s00394-011-0186-3] [Citation(s) in RCA: 86] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2010] [Accepted: 03/14/2011] [Indexed: 01/02/2023]
Abstract
PURPOSE Enzymatic protein hydrolysates of yellow pea seed have been shown to possess high anti-oxidant and anti-bacterial activities. The aim of this work was to confirm the anti-oxidant, anti-inflammatory and immunomodulating activities of an enzymatic protein hydrolysate of yellow field pea seeds. METHODS The anti-oxidant and anti-inflammatory properties of peptides from yellow field pea proteins (Pisum sativum L.) were investigated in LPS/IFN-γ-activated RAW 264.7 NO⁻ macrophages. The immunomodulating potential of pea protein hydrolysate (PPH) was then studied in a murine model. RESULTS Pea protein hydrolysate, after a 12 h pre-treatment, showed significant inhibition of NO production by activated macrophages up to 20%. Moreover, PPH significantly inhibited their secretion of pro-inflammatory cytokines, TNF-α- and IL-6, up to 35 and 80%, respectively. Oral administration of PPH in mice enhanced the phagocytic activity of their peritoneal macrophages and stimulated the gut mucosa immune response. The number of IgA+ cells was elevated in the small intestine lamina propria, accompanied by an increase in the number of IL-4+, IL-10+ and IFN-γ+ cells. This was correlated to up-regulation of IL-6 secretion by small intestine epithelial cells (IEC), probably responsible for B-cell terminal differentiation to IgA-secreting cells. Moreover, PPH might have increased IL-6 production in IECs via the stimulation of toll-like receptors (TLRs) family, especially TLR2 and TLR4 since either anti-TLR2 or anti-TLR4 was able to completely abolish PPH-induced IL-6 secretion. CONCLUSIONS Enzymatic protein degradation confers anti-oxidant, anti-inflammatory and immunomodulating potentials to pea proteins, and the resulted peptides could be used as an alternative therapy for the prevention of inflammatory-related diseases.
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Affiliation(s)
- Fatou Ndiaye
- Department of Nutrition, Faculty of Health Sciences, University of Ottawa, R2057 Roger Guindon Hall, 451 Smyth Road, Ottawa, ON K1H 8M5, Canada
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15
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Hester SN, Donovan SM. Individual and Combined Effects of Nucleotides and Human Milk Oligosaccharides on Proliferation, Apoptosis and Necrosis in a Human Fetal Intestinal Cell Line. ACTA ACUST UNITED AC 2012. [DOI: 10.4236/fns.2012.311205] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
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16
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Intestinal gene expression in pigs: effects of reduced feed intake during weaning and potential impact of dietary components. Nutr Res Rev 2011; 24:155-75. [DOI: 10.1017/s0954422411000047] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
The weaning transition is characterised by morphological, histological and microbial changes, often leading to weaning-associated disorders. These intestinal changes can partly be ascribed to the lack of luminal nutrition arising from the reduced feed intake common in pigs after weaning. It is increasingly becoming clear that changes in the supply with enteral nutrients may have major impacts on intestinal gene expression. Furthermore, the major dietary constituents, i.e. carbohydrates, fatty acids and amino acids, participate in the regulation of intestinal gene expression. However, nutrients may also escape digestion by mammalian enzymes in the upper gastrointestinal tract. These nutrients can be used by the microflora, resulting in the production of bacterial metabolites, for example, SCFA, which may affect intestinal gene expression indirectly. The present review provides an insight on possible effects of reduced feed intake on intestinal gene expression, as it may occur post-weaning. Detailed knowledge on effects of reduced feed intake on intestinal gene expression may help to understand weaning-associated intestinal dysfunctions and diseases. Examples are given of intestinal genes which may be altered in their expression due to supply with specific nutrients. In that way, gene expression could be modulated by dietary means, thereby acting as a potential therapeutic tool. This could be achieved, for example, by influencing genes coding for digestive or absorptive proteins, thus optimising digestive function and metabolism, but also with regard to immune response, or by influencing proliferative processes, thereby enhancing mucosal repair. This would be of special interest when designing a diet to overcome weaning-associated problems.
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Rowland KJ, Brubaker PL. The "cryptic" mechanism of action of glucagon-like peptide-2. Am J Physiol Gastrointest Liver Physiol 2011; 301:G1-8. [PMID: 21527727 DOI: 10.1152/ajpgi.00039.2011] [Citation(s) in RCA: 104] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
Glucagon-like peptide-2 (GLP-2) is a peptide hormone with multiple beneficial effects on the intestine, including expansion of the mucosal surface area through stimulation of crypt cell proliferation, as well as enhancement of nutrient digestion and absorption. Recent advances in clinical trials involving GLP-2 necessitate elucidation of the exact signaling pathways by which GLP-2 acts. In particular, the GLP-2 receptor has been localized to several intestinal cell types that do not include the proliferating crypt cells, and the actions of GLP-2 have thus been linked to a complex network of indirect mediators that induce diverse signaling pathways. The intestinotropic actions of GLP-2 on the colon have been shown to be mediated through the actions of keratinocyte growth factor and insulin-like growth factor (IGF)-2, whereas small intestinal growth has been linked to IGF-1, IGF-2, and ErbB ligands, as well as the IGF-1 receptor and ErbB. The cellular source of these mediators remains unclear, but it likely includes the intestinal subepithelial myofibroblasts. Conversely, the anti-inflammatory and blood flow effects of GLP-2 are dependent on vasoactive intestinal polypeptide released from submucosal enteric neurons and nitric oxide, respectively. Finally, recent studies have suggested that GLP-2 not only modulates intestinal stem cell behavior but may also promote carcinogenesis in models of sporadic colon cancer. Further consideration of the molecular cross-talk and downstream signaling pathways mediating the intestinotropic effects of GLP-2 is clearly warranted.
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Selga E, Pérez-Cano FJ, Franch A, Ramírez-Santana C, Rivero M, Ciudad CJ, Castellote C, Noé V. Gene expression profiles in rat mesenteric lymph nodes upon supplementation with conjugated linoleic acid during gestation and suckling. BMC Genomics 2011; 12:182. [PMID: 21481241 PMCID: PMC3094308 DOI: 10.1186/1471-2164-12-182] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2010] [Accepted: 04/11/2011] [Indexed: 12/25/2022] Open
Abstract
Background Diet plays a role on the development of the immune system, and polyunsaturated fatty acids can modulate the expression of a variety of genes. Human milk contains conjugated linoleic acid (CLA), a fatty acid that seems to contribute to immune development. Indeed, recent studies carried out in our group in suckling animals have shown that the immune function is enhanced after feeding them with an 80:20 isomer mix composed of c9,t11 and t10,c12 CLA. However, little work has been done on the effects of CLA on gene expression, and even less regarding immune system development in early life. Results The expression profile of mesenteric lymph nodes from animals supplemented with CLA during gestation and suckling through dam's milk (Group A) or by oral gavage (Group B), supplemented just during suckling (Group C) and control animals (Group D) was determined with the aid of the specific GeneChip® Rat Genome 230 2.0 (Affymettrix). Bioinformatics analyses were performed using the GeneSpring GX software package v10.0.2 and lead to the identification of 89 genes differentially expressed in all three dietary approaches. Generation of a biological association network evidenced several genes, such as connective tissue growth factor (Ctgf), tissue inhibitor of metalloproteinase 1 (Timp1), galanin (Gal), synaptotagmin 1 (Syt1), growth factor receptor bound protein 2 (Grb2), actin gamma 2 (Actg2) and smooth muscle alpha actin (Acta2), as highly interconnected nodes of the resulting network. Gene underexpression was confirmed by Real-Time RT-PCR. Conclusions Ctgf, Timp1, Gal and Syt1, among others, are genes modulated by CLA supplementation that may have a role on mucosal immune responses in early life.
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Affiliation(s)
- Elisabet Selga
- Department of Biochemistry and Molecular Biology, School of Pharmacy, University of Barcelona, Spain
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The effects of branched-chain amino acid interactions on growth performance, blood metabolites, enzyme kinetics and transcriptomics in weaned pigs. Br J Nutr 2010; 103:964-76. [PMID: 20196890 DOI: 10.1017/s0007114509992212] [Citation(s) in RCA: 95] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
The impact of excess dietary leucine (Leu) was studied in two growth assays with pigs (8-25 kg). In each trial, forty-eight pigs were allotted to one of six dietary groups. The dietary Leu supply increased from treatment L100 to L200 (three increments). To guarantee that interactions between the branched-chain amino acids (BCAA) were not cushioned either surpluses of isoleucine (Ile, expt 1) or valine (Val; expt 2) were avoided. In the fifth treatment, the effects of a simultaneous excess of Leu and Val (expt 1), or of Leu and Ile (expt 2) were investigated. The sixth treatment was a positive control. An increase in dietary Leu decreased growth performance, and increased plasma Leu and serum alpha-keto-isocaproate levels in a linear, dose-dependent manner. Levels of plasma Ile and Val, and of serum alpha-keto-beta-methylvalerate and alpha-keto-isovalerate, indicated increased catabolism. Linear increases in the activity of basal branched-chain alpha-keto acid dehydrogenase in the liver confirmed these findings. No major alterations occurred in the mRNA of branched-chain amino acid catabolism genes. In liver tissue from expt 2, however, the mRNA levels of growth hormone receptor, insulin-like growth factor acid labile subunit and insulin-like growth factor 1 decreased significantly with increasing dietary Leu. In conclusion, excess dietary Leu increased the catabolism of BCAA mainly through posttranscriptional mechanisms. The impact of excess Leu on the growth hormone--insulin-like growth factor-1 axis requires further investigation.
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20
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Abstract
Curcumin is the active ingredient of turmeric. It is widely used as a kitchen spice and food colorant throughout India, Asia and the Western world. Curcumin is a major constituent of curry powder, to which it imparts its characteristic yellow colour. For over 4000 years, curcumin has been used in traditional Asian and African medicine to treat a wide variety of ailments. There is a strong current public interest in naturally occurring plant-based remedies and dietary factors related to health and disease. Curcumin is non-toxic to human subjects at high doses. It is a complex molecule with multiple biological targets and different cellular effects. Recently, its molecular mechanisms of action have been extensively investigated. It has anti-inflammatory, antioxidant and anti-cancer properties. Under some circumstances its effects can be contradictory, with uncertain implications for human treatment. While more studies are warranted to further understand these contradictions, curcumin holds promise as a disease-modifying and chemopreventive agent. We review the evidence for the therapeutic potential of curcumin from in vitro studies, animal models and human clinical trials.
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In vitro studies on the inhibition of colon cancer by butyrate and carnitine. Nutrition 2009; 25:1193-201. [PMID: 19619983 DOI: 10.1016/j.nut.2009.04.008] [Citation(s) in RCA: 44] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2008] [Revised: 04/13/2009] [Accepted: 04/14/2009] [Indexed: 01/19/2023]
Abstract
OBJECTIVE Epidemiologic studies support an association between diet and the incidence of colorectal cancer. Butyrate, a short-chain fatty acid present in dietary fiber and dairy products, is a potential anticarcinogenic compound. We previously showed that carnitine can enhance the bioavailability of butyrate in vivo. In the present study, we evaluated the effects of butyrate alone and in combination with carnitine on colon cancer cells in vitro, examining proliferation and apoptosis and the molecular mechanisms by which these nutrients may inhibit colon cancer. METHODS Caco-2 cells, a well-established cell model, were incubated with butyrate (2.5-20mM) with or without carnitine (10mM) for various incubation periods. Proliferation was measured by incorporation of (3)H-thymidine, and apoptosis was detected using flow cytometry, and then confirmed by analyzing the presence of single-strand DNA breaks typical of apoptotic cells. Prostaglandin E(2) production was assayed and Bcl-2 and cyclo-oxygenase-2 expressions were examined by western blotting. RESULTS Butyrate and carnitine inhibited Caco-2 cell proliferation (P<0.05) and induced apoptosis (P<0.05). Prostaglandin E(2) production was decreased in treated Caco-2 cells. At the molecular level, the expression of proapoptotic Bax and Bak proteins were increased in cells incubated with butyrate and carnitine, whereas expression of antiapoptotic Bcl-x(L) was decreased. Cyclo-oxygenase-2 expression was decreased in cells incubated with butyrate and carnitine. CONCLUSIONS Butyrate and carnitine inhibit human colon carcinoma cell proliferation and induce apoptosis in human colon carcinoma cells. This is accompanied by an appreciable alteration of the Bax-to-Bcl-x(L) and Bak-to-Bcl-x(L) ratios in favor of apoptosis. This study provides a scientific rationale to study the effects of carnitine and butyrate in colon cancer in vivo.
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22
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Drozdowski LA, Clandinin MT, Thomson ABR. Morphological, kinetic, membrane biochemical and genetic aspects of intestinal enteroplasticity. World J Gastroenterol 2009; 15:774-87. [PMID: 19230039 PMCID: PMC2653378 DOI: 10.3748/wjg.15.774] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
The process of intestinal adaptation (“enteroplasticity”) is complex and multifaceted. Although a number of trophic nutrients and non-nutritive factors have been identified in animal studies, successful, reproducible clinical trials in humans are awaited. Understanding mechanisms underlying this adaptive process may direct research toward strategies that maximize intestinal function and impart a true clinical benefit to patients with short bowel syndrome, or to persons in whom nutrient absorption needs to be maximized. In this review, we consider the morphological, kinetic and membrane biochemical aspects of enteroplasticity, focus on the importance of nutritional factors, provide an overview of the many hormones that may alter the adaptive process, and consider some of the possible molecular profiles. While most of the data is derived from rodent studies, wherever possible, the results of human studies of intestinal enteroplasticity are provided.
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Béaslas O, Cueille C, Delers F, Chateau D, Chambaz J, Rousset M, Carrière V. Sensing of dietary lipids by enterocytes: a new role for SR-BI/CLA-1. PLoS One 2009; 4:e4278. [PMID: 19169357 PMCID: PMC2627924 DOI: 10.1371/journal.pone.0004278] [Citation(s) in RCA: 39] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2008] [Accepted: 12/17/2008] [Indexed: 11/23/2022] Open
Abstract
Background The intestine is responsible for absorbing dietary lipids and delivering them to the organism as triglyceride-rich lipoproteins (TRL). It is important to determine how this process is regulated in enterocytes, the absorptive cells of the intestine, as prolonged postprandial hypertriglyceridemia is a known risk factor for atherosclerosis. During the postprandial period, dietary lipids, mostly triglycerides (TG) hydrolyzed by pancreatic enzymes, are combined with bile products and reach the apical membrane of enterocytes as postprandial micelles (PPM). Our aim was to determine whether these micelles induce, in enterocytes, specific early cell signaling events that could control the processes leading to TRL secretion. Methodology/Principal Findings The effects of supplying PPM to the apex of Caco-2/TC7 enterocytes were analyzed. Micelles devoid of TG hydrolysis products, like those present in the intestinal lumen in the interprandial period, were used as controls. The apical delivery of PPM specifically induced a number of cellular events that are not induced by interprandial micelles. These early events included the trafficking of apolipoprotein B, a structural component of TRL, from apical towards secretory domains, and the rapid, dose-dependent activation of ERK and p38MAPK. PPM supply induced the scavenger receptor SR-BI/CLA-1 to cluster at the apical brush border membrane and to move from non-raft to raft domains. Competition, inhibition or knockdown of SR-BI/CLA-1 impaired the PPM-dependent apoB trafficking and ERK activation. Conclusions/Significance These results are the first evidence that enterocytes specifically sense postprandial dietary lipid-containing micelles. SR-BI/CLA-1 is involved in this process and could be a target for further study with a view to modifying intestinal TRL secretion early in the control pathway.
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Affiliation(s)
- Olivier Béaslas
- Université Pierre et Marie Curie - Paris 6, UMR S 872, Les Cordeliers, Paris, France
- INSERM, U 872, Paris, France
- Université Paris Descartes, UMR S 872, Paris, France
| | - Carine Cueille
- Université Pierre et Marie Curie - Paris 6, UMR S 872, Les Cordeliers, Paris, France
- INSERM, U 872, Paris, France
- Université Paris Descartes, UMR S 872, Paris, France
| | - François Delers
- Université Pierre et Marie Curie - Paris 6, UMR S 872, Les Cordeliers, Paris, France
- INSERM, U 872, Paris, France
- Université Paris Descartes, UMR S 872, Paris, France
| | - Danielle Chateau
- Université Pierre et Marie Curie - Paris 6, UMR S 872, Les Cordeliers, Paris, France
- INSERM, U 872, Paris, France
- Université Paris Descartes, UMR S 872, Paris, France
| | - Jean Chambaz
- Université Pierre et Marie Curie - Paris 6, UMR S 872, Les Cordeliers, Paris, France
- INSERM, U 872, Paris, France
- Université Paris Descartes, UMR S 872, Paris, France
| | - Monique Rousset
- Université Pierre et Marie Curie - Paris 6, UMR S 872, Les Cordeliers, Paris, France
- INSERM, U 872, Paris, France
- Université Paris Descartes, UMR S 872, Paris, France
| | - Véronique Carrière
- Université Pierre et Marie Curie - Paris 6, UMR S 872, Les Cordeliers, Paris, France
- INSERM, U 872, Paris, France
- Université Paris Descartes, UMR S 872, Paris, France
- * E-mail:
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Pérez-Cano FJ, Ramírez-Santana C, Molero-Luís M, Castell M, Rivero M, Castellote C, Franch À. Mucosal IgA increase in rats by continuous CLA feeding during suckling and early infancy. J Lipid Res 2008; 50:467-476. [PMID: 18824724 DOI: 10.1194/jlr.m800356-jlr200] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
The aim of this work was to establish the effect of the cis9,trans11 conjugated linoleic acid (CLA) isomer on mucosal immunity during early life in rats, a period when mucosal immunoglobulin production is poorly developed, as is also the case in humans. CLA supplementation was performed during three life periods: gestation, suckling, and early infancy. The immune status of supplemented animals was evaluated at two time points: at the end of the suckling period (21-day-old rats) and 1 week after weaning (28-day-old rats). Secretory IgA was quantified in intestinal washes from 28-day-old rats by ELISA technique. IgA, TGFbeta, and PPARgamma mRNA expression was measured in small intestine and colon by real time PCR, using Taqman specific probes and primers. IgA mucosal production was enhanced in animals supplemented with CLA during suckling and early infancy: in 28-day-old rats, IgA mRNA expression was increased in small intestine and colon by approximately 6- and 4-fold, respectively, and intestinal IgA protein by approximately 2-fold. TGFbeta gene expression was independent of age and type of tissue considered, and was not modified by dietary CLA. Gene expression of PPARgamma, a possible mediator of CLA's effects was also upregulated in animals receiving CLA during early life. In conclusion, dietary supplementation with CLA during suckling and extended to early infancy enhances development of the intestinal immune response in rats.
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Affiliation(s)
- Francisco J Pérez-Cano
- F. J. Pérez-Cano and C. Ramírez-Santana contributed equally to this work; Department of Physiology, Faculty of Pharmacy, University of Barcelona, Barcelona, Spain.
| | - Carolina Ramírez-Santana
- F. J. Pérez-Cano and C. Ramírez-Santana contributed equally to this work; Department of Physiology, Faculty of Pharmacy, University of Barcelona, Barcelona, Spain
| | - Marta Molero-Luís
- Department of Physiology, Faculty of Pharmacy, University of Barcelona, Barcelona, Spain
| | - Margarida Castell
- Department of Physiology, Faculty of Pharmacy, University of Barcelona, Barcelona, Spain
| | - Montserrat Rivero
- Ordesa Group, Research Department, Scientific Park of Barcelona, Barcelona, Spain CIBER Epidemiología y Salud Pública (CIBERESP), Spain
| | - Cristina Castellote
- Department of Physiology, Faculty of Pharmacy, University of Barcelona, Barcelona, Spain
| | - Àngels Franch
- Department of Physiology, Faculty of Pharmacy, University of Barcelona, Barcelona, Spain
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Abstract
Changes in diet greatly affect the mucosal immune system, particularly in diseases such as Crohn's disease and necrotizing enterocolitis. This article examines the hypothesis that alterations in the luminal environment of the intestine regulate the expression of genes in the enterocyte responsible for signaling to immune cells. Genes expressed by the epithelium orchestrate leukocytes in the lamina propria. For example, chemokine expression in the mouse intestinal epithelium, through transgenic means, induced the recruitment of neutrophils and lymphocytes into intestinal tissues. Diet alters the expression of the genes responsible for signaling by a variety of pathways. The introduction of a normal diet to a weanling mouse up-regulates MHC class II expression through a particular isoform of the class II transactivator, a protein that acts in the nucleus. SCFA concentrations in the intestinal lumen vary markedly with diet. SCFAs increase IL-8 and insulin-like growth factor binding protein-2 expression by inhibiting histone deacetylase activity in the enterocyte. Down-regulation of gene expression by butyrate can act through acetylation of the inhibitory transcription factor Sp3. The review therefore describes a number of molecular pathways, explaining how changes in diet may alter leukocyte recruitment by regulating enterocyte gene expression. Myofibroblasts enhance enterocyte chemotactic activity by cleaving inactive precursors; and myofibroblast genes also are regulated by SCFA. It is likely that other similar regulatory mechanisms remain to be discovered.
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Affiliation(s)
- Ian R Sanderson
- Research Centre for Gastroenterology, Institute of Cell and Molecular Science, Barts and The London, Queen Mary's School of Medicine and Dentistry, University of London, London, UK.
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Neu J. Gastrointestinal development and meeting the nutritional needs of premature infants. Am J Clin Nutr 2007; 85:629S-634S. [PMID: 17284768 DOI: 10.1093/ajcn/85.2.629s] [Citation(s) in RCA: 157] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022] Open
Abstract
The fear of necrotizing enterocolitis and feeding intolerance are major factors inhibiting the use of the enteral route as the primary means of nourishing premature infants. Parenteral nutrition may help to meet many of the nutritional needs of these infants, but has significant detrimental side effects that include intestinal atrophy, sepsis, and increased susceptibility to inflammatory stimuli and systemic inflammatory responses. Being able to minimize the use of the parenteral route and still maintain appropriate nutrition safely would be a major advance in neonatology. At the basis of our inability to use the enteral route is a poorly understood immature gastrointestinal tract. Approaches such as minimal enteral nutrition or trophic feedings may partially alleviate these problems. However, if we are to progress in greater utilization of the gastrointestinal tract, other factors need to be considered. These include the macronutrient composition of minimal enteral or trophic feedings and the microecology of the intestinal lumen. Some of the developmental aspects of the intestine, which include intestinal growth, motor activity, barrier and other innate immune functions, and the microecology of the developing intestine, are briefly reviewed here. The purpose of this review is to suggest important areas of future research in neonatal and developmental gastroenterology that could affect several conditions that are related to immaturity of the gastrointestinal tract.
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Affiliation(s)
- Josef Neu
- University of Florida, Department of Pediatrics, Gainesville, FL, USA.
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27
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Abstract
Intestinal failure is a condition characterized by malnutrition and/or dehydration as a result of the inadequate digestion and absorption of nutrients. The most common cause of intestinal failure is short bowel syndrome, which occurs when the functional gut mass is reduced below the level necessary for adequate nutrient and water absorption. This condition may be congenital, or may be acquired as a result of a massive resection of the small bowel. Following resection, the intestine is capable of adaptation in response to enteral nutrients as well as other trophic stimuli. Identifying factors that may enhance the process of intestinal adaptation is an exciting area of research with important potential clinical applications.
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Abstract
Olive oil is an integral ingredient of the "Mediterranean diet" and accumulating evidence suggests that it may have a potential role in lowering the risk of several types of cancers. The mechanisms by which the cancer-preventing effects of olive oil can be performed, however, are not known. We recently hypothesized that a novel molecular explanation concerning the anti-cancer actions of olive oil may relate to the ability of its monounsaturated fatty acid (MUFA) oleic acid (OA; 18:1n-9) to specifically regulate cancer-related oncogenes. Supporting our hypothesis, exogenous supplementation of cultured breast cancer cells with physiological concentrations of OA was found to suppress the overexpression of HER2 (Her-2/neu, erbB-2), a well-characterized oncogene playing a key role in the etiology, progression and response to chemotherapy and endocrine therapy in approximately 20% of breast carcinomas. OA treatment was also found to synergistically enhance the efficacy of trastuzumab, a humanized monoclonal antibody binding with high affinity to the ectodomain (ECD) of the Her2-coded p185(HER2) oncoprotein. Moreover, OA exposure significantly diminished the proteolytic cleavage of the ECD of HER2 and, consequently, its activation status, a crucial molecular event that determines both the aggressive behavior and the response to trastuzumab of Her2-overexpressing breast carcinomas. Our most recent findings further reveal that OA exposure may suppresses HER2 at the transcriptional level by up-regulating the expression of the Ets protein PEA3 -a DNA-binding protein that specifically blocks HER2 promoter activity- in breast, ovarian and stomach cancer cell lines. This anti-HER2 property of OA offers a previously unrecognized molecular mechanism by which olive oil may regulate the malignant behavior of cancer cells. From a clinical perspective, it could provide an effective means of influencing the outcome of Her-2/neu-overexpressing human carcinomas with poor prognosis. Indeed, OA-induced transcriptional repression of HER2 oncogene may represent a novel genomic explanation linking "Mediterranean diet", olive oil and cancer as it seems to equally operate in various types of Her-2/neu-related carcinomas.
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MESH Headings
- Adult
- Antibodies, Monoclonal/pharmacology
- Antibodies, Monoclonal/therapeutic use
- Antibodies, Monoclonal, Humanized
- Breast Neoplasms/etiology
- Breast Neoplasms/genetics
- Breast Neoplasms/prevention & control
- Cell Line, Tumor/drug effects
- Cell Line, Tumor/enzymology
- Child
- Diet
- Dietary Fats, Unsaturated/pharmacology
- Dietary Fats, Unsaturated/therapeutic use
- Drug Synergism
- Enzyme Activation/drug effects
- Female
- Genes, erbB-2/drug effects
- Humans
- Hyperinsulinism/complications
- Male
- Neoplasm Invasiveness
- Neoplasms/epidemiology
- Neoplasms/prevention & control
- Obesity/complications
- Obesity/epidemiology
- Oleic Acid/pharmacology
- Oleic Acid/therapeutic use
- Olive Oil
- Plant Oils/pharmacology
- Plant Oils/therapeutic use
- Receptor, ErbB-2/antagonists & inhibitors
- Trastuzumab
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Affiliation(s)
- Ramón Colomer
- Medical Oncology, Institut Catala d'Oncologia, Hospital de Girona Dr. Josep Trueta, Girona, Spain.
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29
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Chong K, Joshi S, Jin LT, Shu-Chien AC. Proteomics profiling of epidermal mucus secretion of a cichlid (Symphysodon aequifasciata) demonstrating parental care behavior. Proteomics 2006; 6:2251-8. [PMID: 16385477 DOI: 10.1002/pmic.200500591] [Citation(s) in RCA: 31] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]
Abstract
The discus fish (Symphysodon aequifasciata) is a cichlid demonstrating advanced mode of parental care towards fry. Both male and female fish utilized epidermal mucus secreted from specialized epidermal cells to feed developing fry. We utilized proteomics to compare protein profile from parental and nonparental fish. Gel analysis revealed a total of 35 spots that were up-regulated in parental mucus. In tandem, another 18 spots were uniquely expressed in parental mucus. MS analysis of these spots identified proteins such as fructose biphosphate aldolase, nucleoside diphosphate kinase, and heat shock proteins, which are essential to support energy provision, cell repair and proliferation, stress mediation, and defense mechanism in parental fish during parental-care period. Concurrently, the detection of several antioxidant-related proteins such as thioredoxin peroxidase and hemopexin suggests a need to overcome oxidative stress during hypermucosal production in parental-care behavior. A C-type lectin was also found to be uniquely expressed in parental mucus and could have important role in providing antimicrobial defense to both parental fish and fry. In summary, our study shows that discus mucus proteome undergoes changes in protein expression during parental-care period.
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Affiliation(s)
- Kenny Chong
- School of Biological Sciences, Universiti Sains Malaysia, Minden, Penang, Malaysia
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30
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Daly K, Shirazi-Beechey SP. Microarray analysis of butyrate regulated genes in colonic epithelial cells. DNA Cell Biol 2006; 25:49-62. [PMID: 16405400 DOI: 10.1089/dna.2006.25.49] [Citation(s) in RCA: 121] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Butyrate is a naturally occurring product of colonic microbial fermentation of dietary carbohydrates that escape hydrolysis in the small intestine. Butyrate plays a significant role in the maintenance of colonic tissue homeostasis by regulating the expression of genes associated with the processes of proliferation, differentiation, and apoptosis. Using microarray analysis, we assessed changes in the expression of 19,400 genes in response to butyrate in a human colonic epithelial cell line. Among these, we have identified 221 potentially butyrate- responsive genes specifically associated with the processes of proliferation, differentiation, and apoptosis. Of these genes, 59 are upregulated and 162 downregulated, in accordance with the known modes of action of butyrate. The changes in the expression levels (up- or downregulation) of many of these genes were found to be opposite to that reported in colon cancer tissue, where the intracellular concentration of butyrate would be reduced due to the decline in expression of the colonic butyrate transporter, MCT1.
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Affiliation(s)
- Kristian Daly
- Epithelial Function and Development Group, Department of Veterinary Preclinical Sciences, University of Liverpool, UK
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31
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Abstract
Necrotizing enterocolitis (NEC) is a leading cause of mortality and morbidity in neonatal intensive care units. Here we review selected manifestations of NEC, risk factors involved in its pathophysiology as well as putative mechanisms associated with how an immature gut might be more susceptible to NEC. Treatment and potential preventive strategies are discussed.
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Affiliation(s)
- Josef Neu
- University of Florida, Department of Pediatrics, Gainesville, Florida 32610, USA
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32
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Dommett R, Zilbauer M, George JT, Bajaj-Elliott M. Innate immune defence in the human gastrointestinal tract. Mol Immunol 2005; 42:903-12. [PMID: 15829280 DOI: 10.1016/j.molimm.2004.12.004] [Citation(s) in RCA: 74] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
Abstract
The mucosal surface of the gastrointestinal tract represents a major entry point and ecological niche for many microbes. It forms an important immune barrier, absorbing nutrients, whilst preventing invasion by organisms. Of the extra-ordinarily diverse species that comprise the microbial world, relatively few organisms are able to succeed in breaching this barrier in an otherwise healthy host. The production and secretion of antimicrobial peptides (AMPs) from surface epithelia and circulating immune cells are likely to play a key role in host protection and homeostasis. A number of these peptides are constitutively produced providing resident protection, whereas others are induced during infection and inflammation. In addition to directly eradicating microorganisms, it is becoming increasingly apparent that AMPs are multi-functional with diverse immuno-modulatory properties. This review focuses on three families of AMPs, defensins, cathelicidins, and lysozyme, and discusses their role in mucosal defence.
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Affiliation(s)
- Rachel Dommett
- Infectious Diseases and Microbiology, Institute of Child Health, University of College London, 30 Guilford Street, London WC1N 1EH, UK
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33
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Cuff M, Dyer J, Jones M, Shirazi-Beechey S. The human colonic monocarboxylate transporter Isoform 1: its potential importance to colonic tissue homeostasis. Gastroenterology 2005; 128:676-86. [PMID: 15765403 DOI: 10.1053/j.gastro.2004.12.003] [Citation(s) in RCA: 65] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/02/2022]
Abstract
BACKGROUND & AIMS Butyrate serves as the major source of energy for colonic epithelial cells, and has profound effects on their proliferation, differentiation, and apoptosis. Transport of butyrate across the colonocyte luminal membrane is mediated by the monocarboxylate transporter, MCT1; the expression of which is down-regulated dramatically during colon carcinogenesis. We have proposed that the decline in MCT1 expression during colon carcinogenesis may reduce the intracellular availability of butyrate required to regulate expression of genes associated with the processes maintaining tissue homeostasis within the colonic mucosa. METHODS To test this hypothesis we used the technique of RNA interference to inhibit MCT1 expression specifically, and determined the consequences of this inhibition on the ability of butyrate to exert its recognized effects in vitro using flow cytometry, immunofluorescence, Northern analysis, and Western analysis. RESULTS We show that inhibition of MCT1 expression, and hence butyrate uptake, has profound inhibitory effects on the ability of butyrate to regulate expression of key target genes: p21waf1/cip1 (p21), intestinal alkaline phosphatase (IAP), and cyclin D1, and their associated processes of proliferation and differentiation. In contrast, inhibition of MCT1 expression had no effect on the ability of butyrate to modulate expression of either bcl-XL or bak, and this was reflected in a corresponding lack of effect on butyrate induction of apoptosis. CONCLUSIONS Collectively, these results show the importance of MCT1 to the ability of butyrate to induce cell-cycle arrest and differentiation, and suggest fundamental differences in the mechanisms by which butyrate modulates specific aspects of cell function.
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Affiliation(s)
- Mark Cuff
- Department of Veterinary Preclinical Sciences, University of Liverpool, Liverpool, United Kingdom
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34
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Abstract
The last decade provided evidence that major (glucose, fatty acids, amino acids) or minor (iron, vitamin, etc.) dietary constituents regulated gene expression in an hormonal-independent manner. This review focuses on molecular mechanisms by which fatty acids control the expression genes encoding regulatory protein involved in their own metabolism. Nonesterified fatty acids or their CoA derivatives seem to be the main signals involved in the transcriptional effect of long-chain fatty acids. The effects of fatty acids are mediated either directly owing to their specific binding to various nuclear receptors (PPAR, LXR, HNF-4alpha) leading to changes in the trans-activating activity of these transcription factors, or indirectly as the result of changes in the abundance of regulatory transcription factors (SREBP-1c, ChREBP, etc.). The relative contribution of each transcription factor in fatty acid-induced positive or negative gene expression is discussed.
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Affiliation(s)
- Jean-Paul Pégorier
- Département d'Endocrinologie, Institut Cochin, INSERM U567, CNRS UMR8104, IFR Alfred JOST, Faculté de Médecine Cochin-Port-Royal, 24 rue du Faubourg Saint Jacques, 75014 Paris, France.
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35
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Sanderson IR. Short chain fatty acid regulation of signaling genes expressed by the intestinal epithelium. J Nutr 2004; 134:2450S-2454S. [PMID: 15333741 DOI: 10.1093/jn/134.9.2450s] [Citation(s) in RCA: 86] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/14/2022] Open
Abstract
Changes in diet greatly affect the mucosal immune system, particularly in diseases such as Crohn's disease and necrotizing enterocolitis. This review examines the hypothesis that alterations in the luminal environment of the intestine regulate the expression of genes in the epithelium responsible for signaling to immune cells. Increasing chemokine expression in the mouse intestinal epithelium using transgenic techniques enhances the recruitment of neutrophils and lymphocytes into the intestine. Furthermore, SCFA concentrations in the intestinal lumen vary markedly with diet. SCFAs alter chemokine expression by inhibiting histone deacetylase activity in the enterocyte. The review therefore describes a molecular pathway explaining how changes in diet may alter leukocyte recruitment by regulating enterocyte gene expression. It is likely that other similar pathways remain to be discovered.
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Affiliation(s)
- Ian R Sanderson
- Centre for Adult & Paediatric Gastroenterology, Institute of Cell and Molecular Science, Barts and the London, Queen Mary University of London, London, UK.
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36
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Ashcroft F, Varro A, Dimaline R, Dockray G. Control of expression of the lectin-like protein Reg-1 by gastrin: role of the Rho family GTPase RhoA and a C-rich promoter element. Biochem J 2004; 381:397-403. [PMID: 15109306 PMCID: PMC1133845 DOI: 10.1042/bj20031793] [Citation(s) in RCA: 27] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2003] [Revised: 04/15/2004] [Accepted: 04/26/2004] [Indexed: 01/31/2023]
Abstract
The expression of members of the Reg family of secreted lectin-like proteins is increased in response to stress, inflammation and damage in many tissues. In the stomach, Reg is located in enterochromaffin-like cells, where its expression is stimulated by the gastric hormone gastrin. We have examined the mechanisms by which gastrin stimulates expression of Reg-1. Deletional mutations of 2.1 to 0.1 kb of the rat Reg-1 promoter in a luciferase reporter vector were transiently transfected into gastric cancer AGS-G(R) cells. All promoter fragments tested showed similar relative increases in luciferase expression in response to gastrin (1 nM). The response to gastrin of the smallest (104 bp) construct was 4.2+/-0.4-fold over basal. These responses were reduced by Ro-32-0432, a protein kinase C inhibitor, by C3-transferase, a Clostridium botulinum toxin and a selective inhibitor of the Rho family GTPase RhoA, and by co-transfection with a dominant negative form of RhoA. Co-transfection with a constitutively active form of RhoA stimulated expression 11.6+/-1.7-fold over basal. Mutations through the 104 bp construct identified a C-rich element (C-79CCCTCCC-72) required for responses to gastrin, PKC (protein kinase C) and L63RhoA (the constitutively active form of human RhoA protein containing a glutamine-to-leucine substitution at position 63). EMSAs (electrophoretic-mobility-shift assays) using nuclear extracts of control and gastrin-stimulated AGS-G(R) cells and a probe spanning -86 to -64 bp revealed multiple binding proteins. There was no effect of gastrin on the pattern of binding. Supershift assays indicated that transcription factors Sp1 and Sp3 bound the C-rich sequence. We conclude that gastrin stimulates Reg expression via activation of PKC and RhoA, that a C-rich region (-79 to -72) is critical for the response and that Sp-family transcription factors bind to this region of the promoter.
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Key Words
- gastric epithelium
- growth factor
- reg-1
- rhoa
- sp1/3
- transcription
- cck, cholecystokinin
- cga, chromogranin a
- ecl-cell, enterochromaffin-like cell
- emsa, electrophoretic-mobility-shift assay
- g17, heptadecapeptide gastrin
- il, interleukin
- pai-2, plasminogen activator inhibitor type 2
- parp, poly(adp-ribose) polymerase
- pkc, protein kinase c
- tff1, trefoil factor 1
- tgf, transforming growth factor
- tnf, tumour necrosis factor
- vmat2, vesicular monoamine transporter type 2
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Affiliation(s)
- Felicity J. Ashcroft
- Physiological Laboratory, University of Liverpool, Crown Street, Liverpool L69 3BX, U.K
| | - Andrea Varro
- Physiological Laboratory, University of Liverpool, Crown Street, Liverpool L69 3BX, U.K
| | - Rod Dimaline
- Physiological Laboratory, University of Liverpool, Crown Street, Liverpool L69 3BX, U.K
| | - Graham J. Dockray
- Physiological Laboratory, University of Liverpool, Crown Street, Liverpool L69 3BX, U.K
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37
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Abstract
PURPOSE OF REVIEW The intestine has traditionally been assumed to process food by digestion and absorption. The possibility that the intestine or other genes in the body respond to diet has only slowly been appreciated. RECENT FINDINGS This review examines recent evidence that nutrients act on genes in the intestine and in distant sites such as the brain, liver, and skeletal muscle. The article reviews how nutrients affect genes involved in cancer in the intestine; it also studies dietary effects on inflammatory pathways and changes in the brain. Studies in the liver have given insights as to how amino acids may regulate gene promoter activity. Finally, target of rapamycin, an epigenetic regulator, links nutrition to histone acetylation, a key event in gene expression. SUMMARY The evidence that nutrients regulate gene expression continues to increase.
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Affiliation(s)
- Rachel S Levi
- Departments of aPaediatric, Barts and The London Hospitals, London, UK.
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38
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Thiesen A, Drozdowski L, Iordache C, Neo CC, Woudstra TD, Xenodemetropoulos T, Keelan M, Clandinin MT, Thomson ABR, Wild G. Adaptation following intestinal resection: mechanisms and signals. Best Pract Res Clin Gastroenterol 2003; 17:981-95. [PMID: 14642861 DOI: 10.1016/s1521-6918(03)00097-0] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
The intestine has an inherent ability to adapt morphologically and functionally in response to internal and external environmental changes. The functional adaptations encompass modifications of the brush border membrane fluidity and permeability, as well as up- or down-regulation of carrier-mediated transport. Intestinal adaptation improves the nutritional status following the loss of a major portion of the small intestine, following chronic ingestion of ethanol, following sublethal doses of abdominal irradiation, in diabetes, in pregnancy and lactation, with ageing, and with fasting and malnutrition. Following intestinal resection, morphological and functional changes occur depending upon the extent of the intestine removed, the site studied, and the lipid content of the diet. Therefore, intestinal adaptation has important implications in the survival potential and welfare of the host. An understanding of the mechanisms of, and signals for, intestinal adaptation in the experimental setting forms the basis for the use of management strategies in humans with the short-bowel syndrome.
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Affiliation(s)
- A Thiesen
- Nutrition and Metabolism Research Group, Division of Gastroenterology, Department of Medicine, University of Alberta, 519 Newton Research Building, 205 College Plaza, 8215-112 Street, Edmonton, Alta, Canada T6G 2C2.
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39
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Ogawa H, Rafiee P, Fisher PJ, Johnson NA, Otterson MF, Binion DG. Butyrate modulates gene and protein expression in human intestinal endothelial cells. Biochem Biophys Res Commun 2003; 309:512-9. [PMID: 12963019 DOI: 10.1016/j.bbrc.2003.08.026] [Citation(s) in RCA: 47] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
We hypothesized that sodium butyrate, a product of enteric bacterial fermentation, modulates gene expression in gut microvascular endothelium which plays a central role in mucosal immunity. We examined sodium butyrate's effect on LPS-induced gene and protein expression in primary cultures of human intestinal microvascular endothelial cells. cDNA array analysis revealed that sodium butyrate augmented ICAM-1 mRNA expression, while it inhibited IL-6 and COX-2 expression in response to LPS stimulation. These results were confirmed at the protein level. Prostaglandin E2 production by LPS was also strongly inhibited by butyrate. The pattern of altered gene expression by butyrate was reproduced by the histone deacetylase inhibitor tricostatin A, suggesting that the regulatory mechanism of butyrate on HIMEC gene expression involves histone deacetylase inhibition. IkappaBalpha degradation and NF-kappaB activation were unaffected by butyrate. In addition to effects on epithelium, sodium butyrate modulates the innate mucosal immune response towards LPS through effects on microvascular endothelial function.
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Affiliation(s)
- Hitoshi Ogawa
- Department of Medicine, Digestive Disease Center, Free Radical Research Center, Froedtert Memorial Lutheran Hospital, Milwaukee Veterans Administration Medical Center, Medical College of Wisconsin, Milwaukee, WI 53226, USA
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40
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Delzenne N, Cherbut C, Neyrinck A. Prebiotics: actual and potential effects in inflammatory and malignant colonic diseases. Curr Opin Clin Nutr Metab Care 2003; 6:581-6. [PMID: 12913677 DOI: 10.1097/00075197-200309000-00013] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
PURPOSE OF REVIEW This paper will summarize the most recent clinical and experimental data on the effects of prebiotics in inflammatory and cancerous diseases of the large intestine. RECENT FINDINGS Animal studies, as well as data obtained in in-vitro cell culture systems, have underlined the potential of certain prebiotics to protect against inflammatory and cancerous processes in the large intestine. Clinical trials are now in progress to assess the relevance of these promising results. The biochemical mechanisms are still incompletely deciphered, but both the promotion of lactic acid-producing bacteria and the production of short-chain fatty acids, particularly butyrate, during the fermentation of prebiotics could be key factors. SUMMARY Enteric resident bacteria are involved in inflammatory bowel diseases and may contribute to colonic carcinogenesis. Dietary manipulation of the flora may thus represent a useful aid to prevent or to treat these diseases, and this could be a place for prebiotics. Inulin-like prebiotics have shown encouraging results in animal models, but clinical and epidemiological trials are necessary to define their efficacy in humans. In the next few years, important advances are expected in understanding the interactions between prebiotics, intestinal flora and the colonic mucosa in health and diseases, enabling the improvement of therapy as well as better nutritional handling of susceptible individuals.
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Affiliation(s)
- Nathalie Delzenne
- School of Pharmacy, Université Catholique de Louvain, UCL-PMNT 7369, 73 Avenue Mounier, B-1200 Brussels, Belgium.
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41
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Ohtsuka Y, Sanderson IR. Dextran sulfate sodium-induced inflammation is enhanced by intestinal epithelial cell chemokine expression in mice. Pediatr Res 2003; 53:143-7. [PMID: 12508094 DOI: 10.1203/00006450-200301000-00024] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Dextran sulfate sodium (DSS) induces an inflammatory bowel disease-like colitis in animals. To determine the contribution of epithelium to inflammation in the intestine, we examined the effects of DSS in transgenic mice that specifically secrete macrophage inflammatory protein-2 (MIP-2) from the intestinal epithelium. We first confirmed the production of MIP-2 from intestinal epithelial cells by Western blots in transgenic mice. MIP-2 transgenic mice were therefore an appropriate model to examine the role of epithelial cell chemokines in an inflammatory state induced by DSS. We then examined the neutrophil migration into the intestine and the effect of DSS on this migration by myeloperoxidase staining. There was an increase of myeloperoxidase-positive neutrophils in the intestine from wild-type and transgenic mice after the DSS treatment. Furthermore, the increase of neutrophils under stimulation with DSS was confirmed quantitatively by measuring specific tissue myeloperoxidase activities. It was significantly greater in DSS-treated MIP-2 transgenic mice than in wild-type mice in both the small intestine and colon. These results suggest that the inflammatory effects of DSS on both small intestine and colon are enhanced by MIP-2 secreted by epithelial cells in the transgenic mice. In conclusion, intestinal epithelial cells can act in concert with other inflammatory stimuli in maintaining inflammation.
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Affiliation(s)
- Yoshikazu Ohtsuka
- Department of Adult and Paediatric Gastroenterology, St. Bartholomew's and the Royal London School of Medicine and Dentistry, London, U.K
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42
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Affiliation(s)
- Maria-Stella Serrano
- Department of Pediatrics, Louisiana Health Sciences Center, New Orleans, Louisiana 70112-2822, USA
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43
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Sanderson IR. Feeding genes. J Pediatr Gastroenterol Nutr 2002; 34 Suppl 1:S22-6. [PMID: 12082383 DOI: 10.1097/00005176-200205001-00006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/10/2022]
Affiliation(s)
- Ian R Sanderson
- Pediatric Gastroenterology, Department of Adult and Pediatric Gastroenterology, St. Bartholomew's and the Royal London School of Medicine and Dentistry, United Kingdom.
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44
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Abstract
Neonatal intensive care in the past three decades has provided exciting modalities for improving the survival of critically ill neonates. There remains a great need for improving the quality of life for these survivors. In this article, the role the developing GI tract and its microenvironment play in the well-being of the neonate has been emphasized. Future therapies based on manipulation of the GI tract and its microenvironment by functional foods, immunonutrients, or pharmacologic agents may have effects not only during the neonatal period, but also throughout the individual's entire life.
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Affiliation(s)
- Josef Neu
- Division of Neonatology, Department of Pediatrics, University of Florida, Gainesville, Florida, USA
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45
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Abstract
Supplementation of the conditionally essential amino acid glutamine may be beneficial for individuals who are highly stressed and have minimal energy and protein reserves. This includes elderly individuals, postoperative patients, individuals with cancer and very low birthweight infants. Individuals who are undergoing treatment with catabolic glucocorticoids may also benefit. Unfortunately, confusion exists as to situations in which glutamine may be beneficial because a clearly defined "glutamine deficiency syndrome" has not been described as for some other nutrients. In this review, we will discuss how glutamine affects protein metabolism under certain stressful conditions, how it affects intestinal mucosal integrity and how this might relate to sepsis and systemic inflammation. We will also discuss nutrients that are closely related to glutamine such as glutamate, nucleotides, arginine, glucosamines, and ornithine alpha-ketoglutarate and how and why they might be used as substitutes for glutamine.
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Affiliation(s)
- Josef Neu
- Department of Pediatrics/Division of Neonatology, University of Florida, Gainesville, FL 326-0296, USA.
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46
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Abstract
The intestinal epithelium acts as a barrier to the external environment contained within the lumen of the gut. It also transports solutes for nutrition and for immunological surveillance. The present review develops the hypothesis that changes in diet, through the composition of the lumen environment, alter the expression of genes in the epithelium. These genes include those that encode for proteins that signal to the mucosal immune system. Directly changing the expression of signalling molecules in the intestinal epithelium using transgenic techniques alters immune function. For example, up regulation of the chemokine macrophage inflammatory protein-2 increases neutrophil recruitment. Furthermore, lumen molecules such as short-chain fatty acids regulate chemokine expression by epithelial cells. By this means, the epithelium acts as a transducing monolayer signalling between the contents of the intestine and the mucosal immune system.
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Affiliation(s)
- I R Sanderson
- Department of Adult and Paediatric Gastroenterology, St Bartholomew's and The Royal London School of Medicine and Dentistry, UK.
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47
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Abstract
Enteral nutrition is an established therapeutic option in the treatment of patients with Crohn disease. The mode of action for enteral nutrition remains unknown but research efforts have begun to elucidate the complex interaction between nutritional luminal contents, intestinal epithelium, and mucosal immune response. Trials of novel enteral diet formulations have been conducted to explore the antiinflammatory role of specific nutrients.
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Affiliation(s)
- Mary Zachos
- Division of Gastroenterology and Nutrition, The Hospital for Sick Children, Toronto, Ontario, Canada
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