A model mimicking catabolic inflammatory disease; a controlled randomized study in humans
Inflammatory disease is catabolic and associated with insulin resistance, increased energy expenditure, lipolysis and muscle protein loss. The main contributors to these metabolic adaptations are inflammation, malnutrition and immobilisation. Controlled experimental models incorporating these centra...
Gespeichert in:
| Veröffentlicht in: | PloS one 2020-11, Vol.15 (11), p.e0241274-e0241274 |
|---|---|
| Hauptverfasser: | , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | e0241274 |
|---|---|
| container_issue | 11 |
| container_start_page | e0241274 |
| container_title | PloS one |
| container_volume | 15 |
| creator | Mose, Maike Rittig, Nikolaj Mikkelsen, Ulla Ramer Jessen, Niels Bengtsen, Mads Bisgaard Christensen, Brit Jørgensen, Jens Otto Lunde Møller, Niels |
| description | Inflammatory disease is catabolic and associated with insulin resistance, increased energy expenditure, lipolysis and muscle protein loss. The main contributors to these metabolic adaptations are inflammation, malnutrition and immobilisation. Controlled experimental models incorporating these central elements of hospitalisation are lacking. The aim of this study was to validate such a human experimental model.
In a randomized crossover design, six healthy young men underwent; (i) overnight fast (CTR), or (ii) exposure to systemic lipopolysaccharide (1 ng/kg) combined with 36-hour fast and bed rest (CAT). The difference in insulin sensitivity between CAT and CTR was the main outcome, determined by a hyperinsulinemic euglycemic glucose clamp. Palmitate, glucose, urea, phenylalanine and tyrosine tracers were infused to estimate metabolic shifts during interventions. Indirect calorimetry was used to estimate energy expenditure and substrate oxidation.
Insulin sensitivity was 41% lower in CAT than in CTR (M-value, mg/kg/min): 4.3 ± 0.2 vs 7.3 ± 1.3, p |
| doi_str_mv | 10.1371/journal.pone.0241274 |
| format | Article |
| fullrecord | <record><control><sourceid>gale_plos_</sourceid><recordid>TN_cdi_plos_journals_2457964132</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A640707190</galeid><doaj_id>oai_doaj_org_article_9ff58e609ba342bc91d4f442bec32bf7</doaj_id><sourcerecordid>A640707190</sourcerecordid><originalsourceid>FETCH-LOGICAL-c692t-6a34b124901276692d716fb705d4c429b71436e3c16b0eceefb21efd1e148e5e3</originalsourceid><addsrcrecordid>eNqNk22L1DAQx4so3nn6DUQLguiLXfPUtEUQlsOHhYMDn8BXIU0mu1nTZi9pxfXTm73tHVu5F5IXGSa_-Sczk8mypxjNMS3xm40fQifdfOs7mCPCMCnZvewU15TMOEH0_pF9kj2KcYNQQSvOH2YnlOIC1xU_zX4s8tZrcHlrW6t-2m6VK9nLxjurctsZJ9tW9j7scm0jyAhvc5kr3_XBOwc6D7LTvrV_khn7Qe9STL4eWtnFx9kDI12EJ-N-ln378P7r-afZxeXH5fniYqZ4TfoZl5Q1mLAapQR4cukSc9OUqNBMMVI3JWaUA1WYNwgUgGkIBqMxYFZBAfQse37Q3TofxViVKAgrypozTEkilgdCe7kR22BbGXbCSyuuHT6shAy9VQ5EbUxRAUd1k55FGlVjzQxLFihKGlMmrXfjbUPTglaQKiHdRHR60tm1WPlfouSMoWIv8GoUCP5qgNiL1kYFzskO_HD97gpRVuEqoS_-Qe_ObqRWMiWQWubTvWovKhacoRKVuEaJmt9BpaUh9T19IWOTfxLwehKw7zn87ldyiFEsv3z-f_by-5R9ecSuQbp-Hb0beuu7OAXZAVTBxxjA3BYZI7GfgJtqiP0EiHECUtiz4wbdBt18efoXgjgAsQ</addsrcrecordid><sourcetype>Open Website</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2457964132</pqid></control><display><type>article</type><title>A model mimicking catabolic inflammatory disease; a controlled randomized study in humans</title><source>MEDLINE</source><source>DOAJ Directory of Open Access Journals</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>Public Library of Science (PLoS)</source><source>PubMed Central</source><source>Free Full-Text Journals in Chemistry</source><creator>Mose, Maike ; Rittig, Nikolaj ; Mikkelsen, Ulla Ramer ; Jessen, Niels ; Bengtsen, Mads Bisgaard ; Christensen, Brit ; Jørgensen, Jens Otto Lunde ; Møller, Niels</creator><contributor>Brakenridge, Scott</contributor><creatorcontrib>Mose, Maike ; Rittig, Nikolaj ; Mikkelsen, Ulla Ramer ; Jessen, Niels ; Bengtsen, Mads Bisgaard ; Christensen, Brit ; Jørgensen, Jens Otto Lunde ; Møller, Niels ; Brakenridge, Scott</creatorcontrib><description>Inflammatory disease is catabolic and associated with insulin resistance, increased energy expenditure, lipolysis and muscle protein loss. The main contributors to these metabolic adaptations are inflammation, malnutrition and immobilisation. Controlled experimental models incorporating these central elements of hospitalisation are lacking. The aim of this study was to validate such a human experimental model.
In a randomized crossover design, six healthy young men underwent; (i) overnight fast (CTR), or (ii) exposure to systemic lipopolysaccharide (1 ng/kg) combined with 36-hour fast and bed rest (CAT). The difference in insulin sensitivity between CAT and CTR was the main outcome, determined by a hyperinsulinemic euglycemic glucose clamp. Palmitate, glucose, urea, phenylalanine and tyrosine tracers were infused to estimate metabolic shifts during interventions. Indirect calorimetry was used to estimate energy expenditure and substrate oxidation.
Insulin sensitivity was 41% lower in CAT than in CTR (M-value, mg/kg/min): 4.3 ± 0.2 vs 7.3 ± 1.3, p<0.05. The median (min max) palmitate flux (μmol/min) was higher during CAT than in CTR (257.0 (161.7 365.4) vs 131.6 (92.3 189.4), p = 0.004), and protein kinetics did not differ between interventions. C-reactive peptide (mg/L) was elevated in CAT compared with CTR (30.57 ± 4.08 vs 1.03 ± 0.19, p<0.001). Energy expenditure increased by 6% during CAT compared with CTR (1869 ± 94 vs 1756 ± 58, p = 0.04), CAT having higher lipid oxidation rates (p = 0.01) and lower glucose oxidation rates (p = 0.03). Lipopolysaccharide caused varying abdominal discomfort 2 hours post-injection, which had disappeared the following day.
We found that combined systemic inflammation, fasting and bed rest induced marked insulin resistance and increased energy expenditure and lipolysis, rendering this controlled experimental model suitable for anti-catabolic intervention studies, mimicking clinical conditions.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0241274</identifier><identifier>PMID: 33151986</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Adaptation ; Adult ; Bed rest ; Biological models ; Biology and Life Sciences ; Biomarkers - metabolism ; Biopsy ; Calorimetry ; Catabolism ; Catheters ; Development and progression ; Diabetes ; Disease control ; Endocrinology ; Energy expenditure ; Evaluation ; Fasting ; Glucagon ; Glucose ; Glucose Clamp Technique ; Health aspects ; Hospitals ; Humans ; Immobilization ; Inflammation ; Inflammation - pathology ; Inflammatory diseases ; Insulin ; Insulin Resistance ; Internal medicine ; Kinases ; Kinetics ; Lipid peroxidation ; Lipids ; Lipids - analysis ; Lipolysis ; Lipopolysaccharides ; Malnutrition ; Medicine ; Medicine and Health Sciences ; Metabolism ; Mimicry ; Models, Biological ; Muscle, Skeletal - metabolism ; Muscles ; Oxidation ; Palmitic acid ; Phenylalanine ; Physical Sciences ; Physiological aspects ; Proteins ; Proteins - analysis ; Research and Analysis Methods ; Sensitivity ; Signal Transduction ; Substrates ; Tracers ; Tyrosine ; Urea ; Veins & arteries ; Young Adult</subject><ispartof>PloS one, 2020-11, Vol.15 (11), p.e0241274-e0241274</ispartof><rights>COPYRIGHT 2020 Public Library of Science</rights><rights>2020 Mose et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2020 Mose et al 2020 Mose et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-6a34b124901276692d716fb705d4c429b71436e3c16b0eceefb21efd1e148e5e3</citedby><cites>FETCH-LOGICAL-c692t-6a34b124901276692d716fb705d4c429b71436e3c16b0eceefb21efd1e148e5e3</cites><orcidid>0000-0001-8985-8385 ; 0000-0003-2394-8067</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7644057/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7644057/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2095,2914,23846,27903,27904,53769,53771,79346,79347</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33151986$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Brakenridge, Scott</contributor><creatorcontrib>Mose, Maike</creatorcontrib><creatorcontrib>Rittig, Nikolaj</creatorcontrib><creatorcontrib>Mikkelsen, Ulla Ramer</creatorcontrib><creatorcontrib>Jessen, Niels</creatorcontrib><creatorcontrib>Bengtsen, Mads Bisgaard</creatorcontrib><creatorcontrib>Christensen, Brit</creatorcontrib><creatorcontrib>Jørgensen, Jens Otto Lunde</creatorcontrib><creatorcontrib>Møller, Niels</creatorcontrib><title>A model mimicking catabolic inflammatory disease; a controlled randomized study in humans</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Inflammatory disease is catabolic and associated with insulin resistance, increased energy expenditure, lipolysis and muscle protein loss. The main contributors to these metabolic adaptations are inflammation, malnutrition and immobilisation. Controlled experimental models incorporating these central elements of hospitalisation are lacking. The aim of this study was to validate such a human experimental model.
In a randomized crossover design, six healthy young men underwent; (i) overnight fast (CTR), or (ii) exposure to systemic lipopolysaccharide (1 ng/kg) combined with 36-hour fast and bed rest (CAT). The difference in insulin sensitivity between CAT and CTR was the main outcome, determined by a hyperinsulinemic euglycemic glucose clamp. Palmitate, glucose, urea, phenylalanine and tyrosine tracers were infused to estimate metabolic shifts during interventions. Indirect calorimetry was used to estimate energy expenditure and substrate oxidation.
Insulin sensitivity was 41% lower in CAT than in CTR (M-value, mg/kg/min): 4.3 ± 0.2 vs 7.3 ± 1.3, p<0.05. The median (min max) palmitate flux (μmol/min) was higher during CAT than in CTR (257.0 (161.7 365.4) vs 131.6 (92.3 189.4), p = 0.004), and protein kinetics did not differ between interventions. C-reactive peptide (mg/L) was elevated in CAT compared with CTR (30.57 ± 4.08 vs 1.03 ± 0.19, p<0.001). Energy expenditure increased by 6% during CAT compared with CTR (1869 ± 94 vs 1756 ± 58, p = 0.04), CAT having higher lipid oxidation rates (p = 0.01) and lower glucose oxidation rates (p = 0.03). Lipopolysaccharide caused varying abdominal discomfort 2 hours post-injection, which had disappeared the following day.
We found that combined systemic inflammation, fasting and bed rest induced marked insulin resistance and increased energy expenditure and lipolysis, rendering this controlled experimental model suitable for anti-catabolic intervention studies, mimicking clinical conditions.</description><subject>Adaptation</subject><subject>Adult</subject><subject>Bed rest</subject><subject>Biological models</subject><subject>Biology and Life Sciences</subject><subject>Biomarkers - metabolism</subject><subject>Biopsy</subject><subject>Calorimetry</subject><subject>Catabolism</subject><subject>Catheters</subject><subject>Development and progression</subject><subject>Diabetes</subject><subject>Disease control</subject><subject>Endocrinology</subject><subject>Energy expenditure</subject><subject>Evaluation</subject><subject>Fasting</subject><subject>Glucagon</subject><subject>Glucose</subject><subject>Glucose Clamp Technique</subject><subject>Health aspects</subject><subject>Hospitals</subject><subject>Humans</subject><subject>Immobilization</subject><subject>Inflammation</subject><subject>Inflammation - pathology</subject><subject>Inflammatory diseases</subject><subject>Insulin</subject><subject>Insulin Resistance</subject><subject>Internal medicine</subject><subject>Kinases</subject><subject>Kinetics</subject><subject>Lipid peroxidation</subject><subject>Lipids</subject><subject>Lipids - analysis</subject><subject>Lipolysis</subject><subject>Lipopolysaccharides</subject><subject>Malnutrition</subject><subject>Medicine</subject><subject>Medicine and Health Sciences</subject><subject>Metabolism</subject><subject>Mimicry</subject><subject>Models, Biological</subject><subject>Muscle, Skeletal - metabolism</subject><subject>Muscles</subject><subject>Oxidation</subject><subject>Palmitic acid</subject><subject>Phenylalanine</subject><subject>Physical Sciences</subject><subject>Physiological aspects</subject><subject>Proteins</subject><subject>Proteins - analysis</subject><subject>Research and Analysis Methods</subject><subject>Sensitivity</subject><subject>Signal Transduction</subject><subject>Substrates</subject><subject>Tracers</subject><subject>Tyrosine</subject><subject>Urea</subject><subject>Veins & arteries</subject><subject>Young Adult</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>DOA</sourceid><recordid>eNqNk22L1DAQx4so3nn6DUQLguiLXfPUtEUQlsOHhYMDn8BXIU0mu1nTZi9pxfXTm73tHVu5F5IXGSa_-Sczk8mypxjNMS3xm40fQifdfOs7mCPCMCnZvewU15TMOEH0_pF9kj2KcYNQQSvOH2YnlOIC1xU_zX4s8tZrcHlrW6t-2m6VK9nLxjurctsZJ9tW9j7scm0jyAhvc5kr3_XBOwc6D7LTvrV_khn7Qe9STL4eWtnFx9kDI12EJ-N-ln378P7r-afZxeXH5fniYqZ4TfoZl5Q1mLAapQR4cukSc9OUqNBMMVI3JWaUA1WYNwgUgGkIBqMxYFZBAfQse37Q3TofxViVKAgrypozTEkilgdCe7kR22BbGXbCSyuuHT6shAy9VQ5EbUxRAUd1k55FGlVjzQxLFihKGlMmrXfjbUPTglaQKiHdRHR60tm1WPlfouSMoWIv8GoUCP5qgNiL1kYFzskO_HD97gpRVuEqoS_-Qe_ObqRWMiWQWubTvWovKhacoRKVuEaJmt9BpaUh9T19IWOTfxLwehKw7zn87ldyiFEsv3z-f_by-5R9ecSuQbp-Hb0beuu7OAXZAVTBxxjA3BYZI7GfgJtqiP0EiHECUtiz4wbdBt18efoXgjgAsQ</recordid><startdate>20201105</startdate><enddate>20201105</enddate><creator>Mose, Maike</creator><creator>Rittig, Nikolaj</creator><creator>Mikkelsen, Ulla Ramer</creator><creator>Jessen, Niels</creator><creator>Bengtsen, Mads Bisgaard</creator><creator>Christensen, Brit</creator><creator>Jørgensen, Jens Otto Lunde</creator><creator>Møller, Niels</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0001-8985-8385</orcidid><orcidid>https://orcid.org/0000-0003-2394-8067</orcidid></search><sort><creationdate>20201105</creationdate><title>A model mimicking catabolic inflammatory disease; a controlled randomized study in humans</title><author>Mose, Maike ; Rittig, Nikolaj ; Mikkelsen, Ulla Ramer ; Jessen, Niels ; Bengtsen, Mads Bisgaard ; Christensen, Brit ; Jørgensen, Jens Otto Lunde ; Møller, Niels</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c692t-6a34b124901276692d716fb705d4c429b71436e3c16b0eceefb21efd1e148e5e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Adaptation</topic><topic>Adult</topic><topic>Bed rest</topic><topic>Biological models</topic><topic>Biology and Life Sciences</topic><topic>Biomarkers - metabolism</topic><topic>Biopsy</topic><topic>Calorimetry</topic><topic>Catabolism</topic><topic>Catheters</topic><topic>Development and progression</topic><topic>Diabetes</topic><topic>Disease control</topic><topic>Endocrinology</topic><topic>Energy expenditure</topic><topic>Evaluation</topic><topic>Fasting</topic><topic>Glucagon</topic><topic>Glucose</topic><topic>Glucose Clamp Technique</topic><topic>Health aspects</topic><topic>Hospitals</topic><topic>Humans</topic><topic>Immobilization</topic><topic>Inflammation</topic><topic>Inflammation - pathology</topic><topic>Inflammatory diseases</topic><topic>Insulin</topic><topic>Insulin Resistance</topic><topic>Internal medicine</topic><topic>Kinases</topic><topic>Kinetics</topic><topic>Lipid peroxidation</topic><topic>Lipids</topic><topic>Lipids - analysis</topic><topic>Lipolysis</topic><topic>Lipopolysaccharides</topic><topic>Malnutrition</topic><topic>Medicine</topic><topic>Medicine and Health Sciences</topic><topic>Metabolism</topic><topic>Mimicry</topic><topic>Models, Biological</topic><topic>Muscle, Skeletal - metabolism</topic><topic>Muscles</topic><topic>Oxidation</topic><topic>Palmitic acid</topic><topic>Phenylalanine</topic><topic>Physical Sciences</topic><topic>Physiological aspects</topic><topic>Proteins</topic><topic>Proteins - analysis</topic><topic>Research and Analysis Methods</topic><topic>Sensitivity</topic><topic>Signal Transduction</topic><topic>Substrates</topic><topic>Tracers</topic><topic>Tyrosine</topic><topic>Urea</topic><topic>Veins & arteries</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Mose, Maike</creatorcontrib><creatorcontrib>Rittig, Nikolaj</creatorcontrib><creatorcontrib>Mikkelsen, Ulla Ramer</creatorcontrib><creatorcontrib>Jessen, Niels</creatorcontrib><creatorcontrib>Bengtsen, Mads Bisgaard</creatorcontrib><creatorcontrib>Christensen, Brit</creatorcontrib><creatorcontrib>Jørgensen, Jens Otto Lunde</creatorcontrib><creatorcontrib>Møller, Niels</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Opposing Viewpoints</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological & Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Materials Science & Engineering Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies & Aerospace Collection</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Meteorological & Geoastrophysical Abstracts - Academic</collection><collection>ProQuest Engineering Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Agricultural Science Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Engineering Database</collection><collection>Nursing & Allied Health Premium</collection><collection>Advanced Technologies & Aerospace Database</collection><collection>ProQuest Advanced Technologies & Aerospace Collection</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Environmental Science Database</collection><collection>Materials Science Collection</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>Engineering Collection</collection><collection>Environmental Science Collection</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Mose, Maike</au><au>Rittig, Nikolaj</au><au>Mikkelsen, Ulla Ramer</au><au>Jessen, Niels</au><au>Bengtsen, Mads Bisgaard</au><au>Christensen, Brit</au><au>Jørgensen, Jens Otto Lunde</au><au>Møller, Niels</au><au>Brakenridge, Scott</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A model mimicking catabolic inflammatory disease; a controlled randomized study in humans</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2020-11-05</date><risdate>2020</risdate><volume>15</volume><issue>11</issue><spage>e0241274</spage><epage>e0241274</epage><pages>e0241274-e0241274</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Inflammatory disease is catabolic and associated with insulin resistance, increased energy expenditure, lipolysis and muscle protein loss. The main contributors to these metabolic adaptations are inflammation, malnutrition and immobilisation. Controlled experimental models incorporating these central elements of hospitalisation are lacking. The aim of this study was to validate such a human experimental model.
In a randomized crossover design, six healthy young men underwent; (i) overnight fast (CTR), or (ii) exposure to systemic lipopolysaccharide (1 ng/kg) combined with 36-hour fast and bed rest (CAT). The difference in insulin sensitivity between CAT and CTR was the main outcome, determined by a hyperinsulinemic euglycemic glucose clamp. Palmitate, glucose, urea, phenylalanine and tyrosine tracers were infused to estimate metabolic shifts during interventions. Indirect calorimetry was used to estimate energy expenditure and substrate oxidation.
Insulin sensitivity was 41% lower in CAT than in CTR (M-value, mg/kg/min): 4.3 ± 0.2 vs 7.3 ± 1.3, p<0.05. The median (min max) palmitate flux (μmol/min) was higher during CAT than in CTR (257.0 (161.7 365.4) vs 131.6 (92.3 189.4), p = 0.004), and protein kinetics did not differ between interventions. C-reactive peptide (mg/L) was elevated in CAT compared with CTR (30.57 ± 4.08 vs 1.03 ± 0.19, p<0.001). Energy expenditure increased by 6% during CAT compared with CTR (1869 ± 94 vs 1756 ± 58, p = 0.04), CAT having higher lipid oxidation rates (p = 0.01) and lower glucose oxidation rates (p = 0.03). Lipopolysaccharide caused varying abdominal discomfort 2 hours post-injection, which had disappeared the following day.
We found that combined systemic inflammation, fasting and bed rest induced marked insulin resistance and increased energy expenditure and lipolysis, rendering this controlled experimental model suitable for anti-catabolic intervention studies, mimicking clinical conditions.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>33151986</pmid><doi>10.1371/journal.pone.0241274</doi><tpages>e0241274</tpages><orcidid>https://orcid.org/0000-0001-8985-8385</orcidid><orcidid>https://orcid.org/0000-0003-2394-8067</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2020-11, Vol.15 (11), p.e0241274-e0241274 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_2457964132 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Public Library of Science (PLoS); PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Adaptation Adult Bed rest Biological models Biology and Life Sciences Biomarkers - metabolism Biopsy Calorimetry Catabolism Catheters Development and progression Diabetes Disease control Endocrinology Energy expenditure Evaluation Fasting Glucagon Glucose Glucose Clamp Technique Health aspects Hospitals Humans Immobilization Inflammation Inflammation - pathology Inflammatory diseases Insulin Insulin Resistance Internal medicine Kinases Kinetics Lipid peroxidation Lipids Lipids - analysis Lipolysis Lipopolysaccharides Malnutrition Medicine Medicine and Health Sciences Metabolism Mimicry Models, Biological Muscle, Skeletal - metabolism Muscles Oxidation Palmitic acid Phenylalanine Physical Sciences Physiological aspects Proteins Proteins - analysis Research and Analysis Methods Sensitivity Signal Transduction Substrates Tracers Tyrosine Urea Veins & arteries Young Adult |
| title | A model mimicking catabolic inflammatory disease; a controlled randomized study in humans |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-25T13%3A35%3A49IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=A%20model%20mimicking%20catabolic%20inflammatory%20disease;%20a%20controlled%20randomized%20study%20in%20humans&rft.jtitle=PloS%20one&rft.au=Mose,%20Maike&rft.date=2020-11-05&rft.volume=15&rft.issue=11&rft.spage=e0241274&rft.epage=e0241274&rft.pages=e0241274-e0241274&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0241274&rft_dat=%3Cgale_plos_%3EA640707190%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2457964132&rft_id=info:pmid/33151986&rft_galeid=A640707190&rft_doaj_id=oai_doaj_org_article_9ff58e609ba342bc91d4f442bec32bf7&rfr_iscdi=true |