Inflammation-mediated muscle metabolic dysregulation local and remote to the site of major abdominal surgery
Postoperative hyperglycaemia is common in patients having major surgery and is associated with adverse outcomes. This study aimed to determine whether bacteraemia contributed to postoperative systemic inflammation, and whether increases in the expression of muscle mRNAs and proteins reflecting incre...
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| Veröffentlicht in: | Clinical nutrition (Edinburgh, Scotland) Scotland), 2018-12, Vol.37 (6), p.2178-2185 |
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| creator | Varadhan, Krishna K. Constantin-Teodosiu, Dumitru Constantin, Despina Greenhaff, Paul L. Lobo, Dileep N. |
| description | Postoperative hyperglycaemia is common in patients having major surgery and is associated with adverse outcomes. This study aimed to determine whether bacteraemia contributed to postoperative systemic inflammation, and whether increases in the expression of muscle mRNAs and proteins reflecting increased muscle inflammation, atrophy and impaired carbohydrate oxidation were evident at the time of surgery, and both local and distant to the site of trauma, and could be associated with impaired glucoregulation.
Fifteen adult patients without diabetes undergoing major abdominal surgery participated in this observational study set in a university teaching hospital. Arterialised-venous blood samples and muscle biopsies were obtained before and after major elective abdominal surgery, from sites local (rectus abdominis – RA) and remote to the site of surgery (vastus lateralis – VL). The main outcome measures included blood glucose concentrations, gut permeability and changes in expression of muscle mRNAs and proteins linked to inflammation and glucose regulation.
Immediately postoperatively, RA demonstrated markedly increased mRNA expression levels of cathepsin-L (7.5-fold, P |
| doi_str_mv | 10.1016/j.clnu.2017.10.020 |
| format | Article |
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Fifteen adult patients without diabetes undergoing major abdominal surgery participated in this observational study set in a university teaching hospital. Arterialised-venous blood samples and muscle biopsies were obtained before and after major elective abdominal surgery, from sites local (rectus abdominis – RA) and remote to the site of surgery (vastus lateralis – VL). The main outcome measures included blood glucose concentrations, gut permeability and changes in expression of muscle mRNAs and proteins linked to inflammation and glucose regulation.
Immediately postoperatively, RA demonstrated markedly increased mRNA expression levels of cathepsin-L (7.5-fold, P < 0.05), FOXO1 (10.5-fold, P < 0.05), MAFbx (11.5-fold, P < 0.01), PDK4 (7.8-fold, P < 0.05), TNF-α (16.5-fold, P < 0.05) and IL-6 (1058-fold, P < 0.001). A similar, albeit blunted, response was observed in VL. Surgery also increased expression of proteins linked to inflammation (IL-6; 6-fold, P < 0.01), protein degradation (MAFbx; 4.5-fold, P < 0.5), and blunted carbohydrate oxidation (PDK4; 4-fold, P < 0.05) in RA but not VL. Increased systemic inflammation (TNF-α, P < 0.05; IL-6, P < 0.001), and impaired postoperative glucose tolerance (P < 0.001), but not bacteraemia (although gut permeability was increased significantly, P < 0.05) or increased plasma cortisol, were noted 48 h postoperatively.
A systemic postoperative proinflammatory response was accompanied by muscle inflammation and metabolic dysregulation both local and remote to the site of surgery, and was not accompanied by bacteraemia.
Registered at http://clinicaltrials.gov (NCT01134809).]]></description><identifier>ISSN: 0261-5614</identifier><identifier>EISSN: 1532-1983</identifier><identifier>DOI: 10.1016/j.clnu.2017.10.020</identifier><identifier>PMID: 29129636</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>Abdomen - surgery ; Abdominal surgery ; Adult ; adults ; atrophy ; bacteremia ; biopsy ; blood glucose ; Blood Glucose - analysis ; blood sampling ; cathepsin L ; cortisol ; Cytokines ; Cytokines - analysis ; Cytokines - metabolism ; diabetes ; digestive system ; Digestive System Physiological Phenomena ; Female ; Gene expression ; glucose ; glucose tolerance ; Herniorrhaphy - adverse effects ; hospitals ; Humans ; hyperglycemia ; Hyperglycemia - etiology ; Hyperglycemia - metabolism ; inflammation ; Inflammation - metabolism ; Insulin - blood ; interleukin-6 ; Male ; messenger RNA ; Metabolic response ; Middle Aged ; Muscle inflammatory responses ; Muscle, Skeletal - chemistry ; Muscle, Skeletal - metabolism ; muscles ; observational studies ; oxidation ; Pancreatectomy - adverse effects ; patients ; permeability ; Postoperative Complications - metabolism ; Postoperative hyperglycaemia ; protein degradation ; proteins ; tumor necrosis factor-alpha</subject><ispartof>Clinical nutrition (Edinburgh, Scotland), 2018-12, Vol.37 (6), p.2178-2185</ispartof><rights>2017 The Authors</rights><rights>Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.</rights><rights>2017 The Authors 2017</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c514t-de5e4f9d2fff147cd286daa4a01ff839820174b34c26a288db5d14ea0c5da24e3</citedby><cites>FETCH-LOGICAL-c514t-de5e4f9d2fff147cd286daa4a01ff839820174b34c26a288db5d14ea0c5da24e3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.clnu.2017.10.020$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>230,314,777,781,882,3537,27905,27906,45976</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29129636$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Varadhan, Krishna K.</creatorcontrib><creatorcontrib>Constantin-Teodosiu, Dumitru</creatorcontrib><creatorcontrib>Constantin, Despina</creatorcontrib><creatorcontrib>Greenhaff, Paul L.</creatorcontrib><creatorcontrib>Lobo, Dileep N.</creatorcontrib><title>Inflammation-mediated muscle metabolic dysregulation local and remote to the site of major abdominal surgery</title><title>Clinical nutrition (Edinburgh, Scotland)</title><addtitle>Clin Nutr</addtitle><description><![CDATA[Postoperative hyperglycaemia is common in patients having major surgery and is associated with adverse outcomes. This study aimed to determine whether bacteraemia contributed to postoperative systemic inflammation, and whether increases in the expression of muscle mRNAs and proteins reflecting increased muscle inflammation, atrophy and impaired carbohydrate oxidation were evident at the time of surgery, and both local and distant to the site of trauma, and could be associated with impaired glucoregulation.
Fifteen adult patients without diabetes undergoing major abdominal surgery participated in this observational study set in a university teaching hospital. Arterialised-venous blood samples and muscle biopsies were obtained before and after major elective abdominal surgery, from sites local (rectus abdominis – RA) and remote to the site of surgery (vastus lateralis – VL). The main outcome measures included blood glucose concentrations, gut permeability and changes in expression of muscle mRNAs and proteins linked to inflammation and glucose regulation.
Immediately postoperatively, RA demonstrated markedly increased mRNA expression levels of cathepsin-L (7.5-fold, P < 0.05), FOXO1 (10.5-fold, P < 0.05), MAFbx (11.5-fold, P < 0.01), PDK4 (7.8-fold, P < 0.05), TNF-α (16.5-fold, P < 0.05) and IL-6 (1058-fold, P < 0.001). A similar, albeit blunted, response was observed in VL. Surgery also increased expression of proteins linked to inflammation (IL-6; 6-fold, P < 0.01), protein degradation (MAFbx; 4.5-fold, P < 0.5), and blunted carbohydrate oxidation (PDK4; 4-fold, P < 0.05) in RA but not VL. Increased systemic inflammation (TNF-α, P < 0.05; IL-6, P < 0.001), and impaired postoperative glucose tolerance (P < 0.001), but not bacteraemia (although gut permeability was increased significantly, P < 0.05) or increased plasma cortisol, were noted 48 h postoperatively.
A systemic postoperative proinflammatory response was accompanied by muscle inflammation and metabolic dysregulation both local and remote to the site of surgery, and was not accompanied by bacteraemia.
Registered at http://clinicaltrials.gov (NCT01134809).]]></description><subject>Abdomen - surgery</subject><subject>Abdominal surgery</subject><subject>Adult</subject><subject>adults</subject><subject>atrophy</subject><subject>bacteremia</subject><subject>biopsy</subject><subject>blood glucose</subject><subject>Blood Glucose - analysis</subject><subject>blood sampling</subject><subject>cathepsin L</subject><subject>cortisol</subject><subject>Cytokines</subject><subject>Cytokines - analysis</subject><subject>Cytokines - metabolism</subject><subject>diabetes</subject><subject>digestive system</subject><subject>Digestive System Physiological Phenomena</subject><subject>Female</subject><subject>Gene expression</subject><subject>glucose</subject><subject>glucose tolerance</subject><subject>Herniorrhaphy - adverse effects</subject><subject>hospitals</subject><subject>Humans</subject><subject>hyperglycemia</subject><subject>Hyperglycemia - etiology</subject><subject>Hyperglycemia - metabolism</subject><subject>inflammation</subject><subject>Inflammation - metabolism</subject><subject>Insulin - blood</subject><subject>interleukin-6</subject><subject>Male</subject><subject>messenger RNA</subject><subject>Metabolic response</subject><subject>Middle Aged</subject><subject>Muscle inflammatory responses</subject><subject>Muscle, Skeletal - chemistry</subject><subject>Muscle, Skeletal - metabolism</subject><subject>muscles</subject><subject>observational studies</subject><subject>oxidation</subject><subject>Pancreatectomy - adverse effects</subject><subject>patients</subject><subject>permeability</subject><subject>Postoperative Complications - metabolism</subject><subject>Postoperative hyperglycaemia</subject><subject>protein degradation</subject><subject>proteins</subject><subject>tumor necrosis factor-alpha</subject><issn>0261-5614</issn><issn>1532-1983</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFUU1vFSEUJcbGvlb_gAvD0s08gWGYmcSYmEZtkyZu2jVh4PLKCwwVmCbv35fpq41udAW5nHs4Hwi9p2RLCRWf9lvt52XLCO3rYEsYeYU2tGtZQ8ehfY02hAnadILyU3SW854Q0rX98AadspGyUbRig_zVbL0KQRUX5yaAcaqAwWHJ2gMOUNQUvdPYHHKC3eKfcNhHrTxWs8EJQiyAS8TlDnB29R4tDmofE1aTicHNFZmXtIN0eItOrPIZ3j2f5-j2-7ebi8vm-uePq4uv143uKC-NgQ64HQ2z1lLea8MGYZTiilBrh3YcVsd8arlmQrFhMFNnKAdFdGcU49Ceoy9H3vtlqpY0zCUpL--TCyodZFRO_v0yuzu5iw9SsLEbe1EJPj4TpPhrgVxkcFmD92qGuGRZBdS0q4r-v1Bac-aCD8PKyo5QnWKucdoXRZTItVG5l2ujK32_zuofdenDn15eVn5XWAGfjwCoiT44SDJrB7OuVSbQRZro_sX_CCiztZQ</recordid><startdate>20181201</startdate><enddate>20181201</enddate><creator>Varadhan, Krishna K.</creator><creator>Constantin-Teodosiu, Dumitru</creator><creator>Constantin, Despina</creator><creator>Greenhaff, Paul L.</creator><creator>Lobo, Dileep N.</creator><general>Elsevier Ltd</general><general>Elsevier</general><scope>6I.</scope><scope>AAFTH</scope><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>7X8</scope><scope>7S9</scope><scope>L.6</scope><scope>5PM</scope></search><sort><creationdate>20181201</creationdate><title>Inflammation-mediated muscle metabolic dysregulation local and remote to the site of major abdominal surgery</title><author>Varadhan, Krishna K. ; Constantin-Teodosiu, Dumitru ; Constantin, Despina ; Greenhaff, Paul L. ; Lobo, Dileep N.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c514t-de5e4f9d2fff147cd286daa4a01ff839820174b34c26a288db5d14ea0c5da24e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Abdomen - surgery</topic><topic>Abdominal surgery</topic><topic>Adult</topic><topic>adults</topic><topic>atrophy</topic><topic>bacteremia</topic><topic>biopsy</topic><topic>blood glucose</topic><topic>Blood Glucose - analysis</topic><topic>blood sampling</topic><topic>cathepsin L</topic><topic>cortisol</topic><topic>Cytokines</topic><topic>Cytokines - analysis</topic><topic>Cytokines - metabolism</topic><topic>diabetes</topic><topic>digestive system</topic><topic>Digestive System Physiological Phenomena</topic><topic>Female</topic><topic>Gene expression</topic><topic>glucose</topic><topic>glucose tolerance</topic><topic>Herniorrhaphy - adverse effects</topic><topic>hospitals</topic><topic>Humans</topic><topic>hyperglycemia</topic><topic>Hyperglycemia - etiology</topic><topic>Hyperglycemia - metabolism</topic><topic>inflammation</topic><topic>Inflammation - metabolism</topic><topic>Insulin - blood</topic><topic>interleukin-6</topic><topic>Male</topic><topic>messenger RNA</topic><topic>Metabolic response</topic><topic>Middle Aged</topic><topic>Muscle inflammatory responses</topic><topic>Muscle, Skeletal - chemistry</topic><topic>Muscle, Skeletal - metabolism</topic><topic>muscles</topic><topic>observational studies</topic><topic>oxidation</topic><topic>Pancreatectomy - adverse effects</topic><topic>patients</topic><topic>permeability</topic><topic>Postoperative Complications - metabolism</topic><topic>Postoperative hyperglycaemia</topic><topic>protein degradation</topic><topic>proteins</topic><topic>tumor necrosis factor-alpha</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Varadhan, Krishna K.</creatorcontrib><creatorcontrib>Constantin-Teodosiu, Dumitru</creatorcontrib><creatorcontrib>Constantin, Despina</creatorcontrib><creatorcontrib>Greenhaff, Paul L.</creatorcontrib><creatorcontrib>Lobo, Dileep N.</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>AGRICOLA</collection><collection>AGRICOLA - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Clinical nutrition (Edinburgh, Scotland)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Varadhan, Krishna K.</au><au>Constantin-Teodosiu, Dumitru</au><au>Constantin, Despina</au><au>Greenhaff, Paul L.</au><au>Lobo, Dileep N.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Inflammation-mediated muscle metabolic dysregulation local and remote to the site of major abdominal surgery</atitle><jtitle>Clinical nutrition (Edinburgh, Scotland)</jtitle><addtitle>Clin Nutr</addtitle><date>2018-12-01</date><risdate>2018</risdate><volume>37</volume><issue>6</issue><spage>2178</spage><epage>2185</epage><pages>2178-2185</pages><issn>0261-5614</issn><eissn>1532-1983</eissn><abstract><![CDATA[Postoperative hyperglycaemia is common in patients having major surgery and is associated with adverse outcomes. This study aimed to determine whether bacteraemia contributed to postoperative systemic inflammation, and whether increases in the expression of muscle mRNAs and proteins reflecting increased muscle inflammation, atrophy and impaired carbohydrate oxidation were evident at the time of surgery, and both local and distant to the site of trauma, and could be associated with impaired glucoregulation.
Fifteen adult patients without diabetes undergoing major abdominal surgery participated in this observational study set in a university teaching hospital. Arterialised-venous blood samples and muscle biopsies were obtained before and after major elective abdominal surgery, from sites local (rectus abdominis – RA) and remote to the site of surgery (vastus lateralis – VL). The main outcome measures included blood glucose concentrations, gut permeability and changes in expression of muscle mRNAs and proteins linked to inflammation and glucose regulation.
Immediately postoperatively, RA demonstrated markedly increased mRNA expression levels of cathepsin-L (7.5-fold, P < 0.05), FOXO1 (10.5-fold, P < 0.05), MAFbx (11.5-fold, P < 0.01), PDK4 (7.8-fold, P < 0.05), TNF-α (16.5-fold, P < 0.05) and IL-6 (1058-fold, P < 0.001). A similar, albeit blunted, response was observed in VL. Surgery also increased expression of proteins linked to inflammation (IL-6; 6-fold, P < 0.01), protein degradation (MAFbx; 4.5-fold, P < 0.5), and blunted carbohydrate oxidation (PDK4; 4-fold, P < 0.05) in RA but not VL. Increased systemic inflammation (TNF-α, P < 0.05; IL-6, P < 0.001), and impaired postoperative glucose tolerance (P < 0.001), but not bacteraemia (although gut permeability was increased significantly, P < 0.05) or increased plasma cortisol, were noted 48 h postoperatively.
A systemic postoperative proinflammatory response was accompanied by muscle inflammation and metabolic dysregulation both local and remote to the site of surgery, and was not accompanied by bacteraemia.
Registered at http://clinicaltrials.gov (NCT01134809).]]></abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>29129636</pmid><doi>10.1016/j.clnu.2017.10.020</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; Elsevier ScienceDirect Journals |
| subjects | Abdomen - surgery Abdominal surgery Adult adults atrophy bacteremia biopsy blood glucose Blood Glucose - analysis blood sampling cathepsin L cortisol Cytokines Cytokines - analysis Cytokines - metabolism diabetes digestive system Digestive System Physiological Phenomena Female Gene expression glucose glucose tolerance Herniorrhaphy - adverse effects hospitals Humans hyperglycemia Hyperglycemia - etiology Hyperglycemia - metabolism inflammation Inflammation - metabolism Insulin - blood interleukin-6 Male messenger RNA Metabolic response Middle Aged Muscle inflammatory responses Muscle, Skeletal - chemistry Muscle, Skeletal - metabolism muscles observational studies oxidation Pancreatectomy - adverse effects patients permeability Postoperative Complications - metabolism Postoperative hyperglycaemia protein degradation proteins tumor necrosis factor-alpha |
| title | Inflammation-mediated muscle metabolic dysregulation local and remote to the site of major abdominal surgery |
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