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      Intermittent Bolus Feeding Enhances Organ Growth More Than Continuous Feeding in a Neonatal Piglet Model

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          ABSTRACT

          Background

          Orogastric tube feeding is frequently prescribed for neonates who cannot ingest food normally. In a piglet model of the neonate, greater skeletal muscle growth is sustained by upregulation of translation initiation signaling when nutrition is delivered by intermittent bolus meals, rather than continuously.

          Objectives

          The objective of this study was to determine the long-term effects of feeding frequency on organ growth and the mechanism by which feeding frequency modulates protein anabolism in these organs.

          Methods

          Eighteen neonatal pigs were fed by gastrostomy tube the same amount of a sow milk replacer either by continuous infusion (CON) or on an intermittent bolus schedule (INT). After 21 d of feeding, the pigs were killed without interruption of feeding (CON; = 6) or immediately before (INT-0; = 6) or 60 min after (INT-60; = 6) a meal, and fractional protein synthesis rates and activation indexes of signaling pathways that regulate translation initiation were measured in the heart, jejunum, ileum, kidneys, and liver.

          Results

          Compared with continuous feeding, intermittent feeding stimulated the growth of the liver (+64%), jejunum (+48%), ileum (+40%), heart (+64%), and kidney (+56%). The increases in heart, kidney, jejunum, and ileum masses were proportional to whole body lean weight gain, but liver weight gain was greater in the INT-60 than the CON, and intermediate for the INT-0 group. For the liver and ileum, but not the heart, kidney, and jejunum, INT-60 compared with CON pigs had greater fractional protein synthesis rates (22% and 48%, respectively) and was accompanied by an increase in ribosomal protein S6 kinase 1 and eukaryotic initiation factor 4E binding protein 1 phosphorylation.

          Conclusions

          These results suggest that intermittent bolus compared with continuous orogastric feeding enhances organ growth and that in the ileum and liver, intermittent feeding enhances protein synthesis by stimulating translation initiation.

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          Most cited references53

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          Regulation of translation initiation in eukaryotes: mechanisms and biological targets.

          Translational control in eukaryotic cells is critical for gene regulation during nutrient deprivation and stress, development and differentiation, nervous system function, aging, and disease. We describe recent advances in our understanding of the molecular structures and biochemical functions of the translation initiation machinery and summarize key strategies that mediate general or gene-specific translational control, particularly in mammalian systems.
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            Molecular mechanisms of mTOR-mediated translational control.

            The process of translation requires substantial cellular resources. Cells have therefore evolved complex mechanisms to control overall protein synthesis as well as the translation of specific mRNAs that are crucial for cell growth and proliferation. At the heart of this process is the mammalian target of rapamycin (mTOR) signalling pathway, which senses and responds to nutrient availability, energy sufficiency, stress, hormones and mitogens to modulate protein synthesis. Here, we highlight recent findings on the regulators and effectors of mTOR and discuss specific cases that serve as paradigms for the different modes of mTOR regulation and its control of translation.
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              • Article: not found

              Diurnal Oscillations in Liver Mass and Cell Size Accompany Ribosome Assembly Cycles.

              The liver plays a pivotal role in metabolism and xenobiotic detoxification, processes that must be particularly efficient when animals are active and feed. A major question is how the liver adapts to these diurnal changes in physiology. Here, we show that, in mice, liver mass, hepatocyte size, and protein levels follow a daily rhythm, whose amplitude depends on both feeding-fasting and light-dark cycles. Correlative evidence suggests that the daily oscillation in global protein accumulation depends on a similar fluctuation in ribosome number. Whereas rRNA genes are transcribed at similar rates throughout the day, some newly synthesized rRNAs are polyadenylated and degraded in the nucleus in a robustly diurnal fashion with a phase opposite to that of ribosomal protein synthesis. Based on studies with cultured fibroblasts, we propose that rRNAs not packaged into complete ribosomal subunits are polyadenylated by the poly(A) polymerase PAPD5 and degraded by the nuclear exosome.
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                Author and article information

                Contributors
                Journal
                Curr Dev Nutr
                Curr Dev Nutr
                cdn
                Current Developments in Nutrition
                Oxford University Press
                2475-2991
                24 November 2020
                December 2020
                24 November 2020
                : 4
                : 12
                : nzaa170
                Affiliations
                United States Department of Agriculture/Agricultural Research Service Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine , Houston, TX, USA
                Department of Animal and Poultry Sciences, Virginia Tech , Blacksburg, VA, USA
                United States Department of Agriculture/Agricultural Research Service Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine , Houston, TX, USA
                United States Department of Agriculture/Agricultural Research Service Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine , Houston, TX, USA
                United States Department of Agriculture/Agricultural Research Service Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine , Houston, TX, USA
                Department of Cellular and Molecular Physiology, Penn State College of Medicine , Hershey, PA, USA
                United States Department of Agriculture/Agricultural Research Service Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine , Houston, TX, USA
                United States Department of Agriculture/Agricultural Research Service Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine , Houston, TX, USA
                Author notes
                Address correspondence to TAD (e-mail: tdavis@ 123456bcm.edu )
                Author information
                http://orcid.org/0000-0001-8475-4704
                Article
                nzaa170
                10.1093/cdn/nzaa170
                7751947
                8514204f-e002-4e3a-8663-40ea9613c655
                © The Author(s) 2020. Published by Oxford University Press on behalf of the American Society for Nutrition.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License ( http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@ 123456oup.com

                History
                : 17 September 2020
                : 06 November 2020
                : 13 November 2020
                Page count
                Pages: 10
                Funding
                Funded by: National Institute of Arthritis and Musculoskeletal and Skin Diseases, DOI 10.13039/100000069;
                Award ID: AR044474
                Award ID: AR46308
                Funded by: National Institute of Child Health and Human Development, DOI 10.13039/100000071;
                Award ID: HD072891
                Award ID: HD085573
                Award ID: HD099080
                Funded by: National Institute of Diabetes and Digestive and Kidney Diseases, DOI 10.13039/100000062;
                Award ID: DK15658
                Funded by: United States Department of Agriculture, DOI 10.13039/100000199;
                Award ID: 2013-67015-20438
                Funded by: USDA, DOI 10.13039/100000199;
                Award ID: 3092-51000-060
                Categories
                ORIGINAL RESEARCH
                Maternal and Pediatric Nutrition
                AcademicSubjects/MED00060

                neonate,nutrition,pig model,liver,translation initiation,protein synthesis

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