Glycine and urea kinetics in nonalcoholic steatohepatitis in human: effect of intralipid infusion
The rates of oxidation of glycine and ureagenesis were quantified in the basal state and in response to an intravenous infusion of intralipid with heparin (IL) in healthy subjects (n = 8) and in subjects with nonalcoholic steatohepatitis (NASH) (n = 6). During fasting, no significant difference in w...
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creator | Dasarathy, Srinivasan Kasumov, Takhar Edmison, John M Gruca, Lourdes L Bennett, Carole Duenas, Clarita Marczewski, Susan McCullough, Arthur J Hanson, Richard W Kalhan, Satish C |
description | The rates of oxidation of glycine and ureagenesis were quantified in the basal state and in response to an intravenous infusion of intralipid with heparin (IL) in healthy subjects (n = 8) and in subjects with nonalcoholic steatohepatitis (NASH) (n = 6). During fasting, no significant difference in weight-specific rate of appearance (R(a)) of glycine, glycine oxidation, and urea synthesis was observed. Intralipid infusion resulted in a significant increase in plasma beta-hydroxybutyrate in both groups. The correlation between free fatty acids and beta-hydroxybutyrate concentration in plasma was 0.94 in NASH compared with 0.4 in controls, indicating greater hepatic fatty acid oxidation in NASH. Intralipid infusion resulted in a significant decrease in urea synthesis and glycine R(a) in both groups and did not impact glycine oxidation. The fractional contribution of glycine carbon to serine was lower in subjects with NASH before and after IL infusion. In contrast, the fractional contribution of serine carbon to cystathionine was higher in NASH before and following IL infusion. These results suggest that hepatic fatty acid oxidation is higher in NASH compared with controls and that glycine oxidation and urea synthesis are not altered. An increase in oxidative stress, induced by a higher rate of fatty acid oxidation in NASH, may have caused an increase in the contribution of serine to cystathionine to meet the higher demands for glutathione. |
doi_str_mv | 10.1152/ajpgi.00042.2009 |
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During fasting, no significant difference in weight-specific rate of appearance (R(a)) of glycine, glycine oxidation, and urea synthesis was observed. Intralipid infusion resulted in a significant increase in plasma beta-hydroxybutyrate in both groups. The correlation between free fatty acids and beta-hydroxybutyrate concentration in plasma was 0.94 in NASH compared with 0.4 in controls, indicating greater hepatic fatty acid oxidation in NASH. Intralipid infusion resulted in a significant decrease in urea synthesis and glycine R(a) in both groups and did not impact glycine oxidation. The fractional contribution of glycine carbon to serine was lower in subjects with NASH before and after IL infusion. In contrast, the fractional contribution of serine carbon to cystathionine was higher in NASH before and following IL infusion. These results suggest that hepatic fatty acid oxidation is higher in NASH compared with controls and that glycine oxidation and urea synthesis are not altered. An increase in oxidative stress, induced by a higher rate of fatty acid oxidation in NASH, may have caused an increase in the contribution of serine to cystathionine to meet the higher demands for glutathione.</description><identifier>ISSN: 0193-1857</identifier><identifier>EISSN: 1522-1547</identifier><identifier>DOI: 10.1152/ajpgi.00042.2009</identifier><identifier>PMID: 19571235</identifier><identifier>CODEN: APGPDF</identifier><language>eng</language><publisher>United States: American Physiological Society</publisher><subject>3-Hydroxybutyric Acid - blood ; Adult ; Aged ; Amino acids ; Case-Control Studies ; Cystathionine - blood ; Fasting - blood ; Fat Emulsions, Intravenous - administration & dosage ; Fat Emulsions, Intravenous - metabolism ; Fatty acids ; Fatty Acids, Nonesterified - blood ; Fatty Liver - metabolism ; Female ; Glutathione - blood ; Glycine - blood ; Humans ; Infusions, Intravenous ; Kinetics ; Liver - metabolism ; Liver and Biliary Tract ; Liver diseases ; Male ; Metabolism ; Middle Aged ; Oxidation ; Oxidation-Reduction ; Oxidative Stress ; Postprandial Period ; Protein synthesis ; Serine - blood ; Urea - blood ; Young Adult</subject><ispartof>American journal of physiology: Gastrointestinal and liver physiology, 2009-09, Vol.297 (3), p.G567-G575</ispartof><rights>Copyright American Physiological Society Sep 2009</rights><rights>Copyright © 2009, American Physiological Society 2009</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c487t-2869f1923f94d3a20af9bc5edf8bb738db6172098ad143206d72553efa68e89c3</citedby><cites>FETCH-LOGICAL-c487t-2869f1923f94d3a20af9bc5edf8bb738db6172098ad143206d72553efa68e89c3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,778,782,883,3028,27911,27912</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19571235$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Dasarathy, Srinivasan</creatorcontrib><creatorcontrib>Kasumov, Takhar</creatorcontrib><creatorcontrib>Edmison, John M</creatorcontrib><creatorcontrib>Gruca, Lourdes L</creatorcontrib><creatorcontrib>Bennett, Carole</creatorcontrib><creatorcontrib>Duenas, Clarita</creatorcontrib><creatorcontrib>Marczewski, Susan</creatorcontrib><creatorcontrib>McCullough, Arthur J</creatorcontrib><creatorcontrib>Hanson, Richard W</creatorcontrib><creatorcontrib>Kalhan, Satish C</creatorcontrib><title>Glycine and urea kinetics in nonalcoholic steatohepatitis in human: effect of intralipid infusion</title><title>American journal of physiology: Gastrointestinal and liver physiology</title><addtitle>Am J Physiol Gastrointest Liver Physiol</addtitle><description>The rates of oxidation of glycine and ureagenesis were quantified in the basal state and in response to an intravenous infusion of intralipid with heparin (IL) in healthy subjects (n = 8) and in subjects with nonalcoholic steatohepatitis (NASH) (n = 6). During fasting, no significant difference in weight-specific rate of appearance (R(a)) of glycine, glycine oxidation, and urea synthesis was observed. Intralipid infusion resulted in a significant increase in plasma beta-hydroxybutyrate in both groups. The correlation between free fatty acids and beta-hydroxybutyrate concentration in plasma was 0.94 in NASH compared with 0.4 in controls, indicating greater hepatic fatty acid oxidation in NASH. Intralipid infusion resulted in a significant decrease in urea synthesis and glycine R(a) in both groups and did not impact glycine oxidation. The fractional contribution of glycine carbon to serine was lower in subjects with NASH before and after IL infusion. In contrast, the fractional contribution of serine carbon to cystathionine was higher in NASH before and following IL infusion. These results suggest that hepatic fatty acid oxidation is higher in NASH compared with controls and that glycine oxidation and urea synthesis are not altered. An increase in oxidative stress, induced by a higher rate of fatty acid oxidation in NASH, may have caused an increase in the contribution of serine to cystathionine to meet the higher demands for glutathione.</description><subject>3-Hydroxybutyric Acid - blood</subject><subject>Adult</subject><subject>Aged</subject><subject>Amino acids</subject><subject>Case-Control Studies</subject><subject>Cystathionine - blood</subject><subject>Fasting - blood</subject><subject>Fat Emulsions, Intravenous - administration & dosage</subject><subject>Fat Emulsions, Intravenous - metabolism</subject><subject>Fatty acids</subject><subject>Fatty Acids, Nonesterified - blood</subject><subject>Fatty Liver - metabolism</subject><subject>Female</subject><subject>Glutathione - blood</subject><subject>Glycine - blood</subject><subject>Humans</subject><subject>Infusions, Intravenous</subject><subject>Kinetics</subject><subject>Liver - metabolism</subject><subject>Liver and Biliary Tract</subject><subject>Liver diseases</subject><subject>Male</subject><subject>Metabolism</subject><subject>Middle Aged</subject><subject>Oxidation</subject><subject>Oxidation-Reduction</subject><subject>Oxidative Stress</subject><subject>Postprandial Period</subject><subject>Protein synthesis</subject><subject>Serine - blood</subject><subject>Urea - blood</subject><subject>Young Adult</subject><issn>0193-1857</issn><issn>1522-1547</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdkctP3DAQxi3UCrbAnVMV9dBbtn7Esc0BCSEelZB6ac_WxLFZL1k7xE4l_vt6H2oLJ49nvvk0Mz-ELgheEsLpN1iPT36JMW7okmKsjtCipGlNeCM-oAUmitVEcnGCPqW0LjpOCTlGJ0RxQSjjCwT3w6vxwVYQ-mqeLFTP5Ze9SZUPVYgBBhNXcfCmStlCjis7QvbZ7-qreQPhsrLOWZOr6EouTzD40fcldHPyMZyhjw6GZM8P7yn6dXf78-ahfvxx__3m-rE2jRS5prJVjijKnGp6BhSDU53htney6wSTfdcSQbGS0JOGUdz2gnLOrINWWqkMO0VXe99x7ja2N3Y3ih4nv4HpVUfw-m0l-JV-ir81FUxJIorB14PBFF9mm7Le-GTsMECwcU66FS1pGVdF-OWdcB3nqVwqacool6wVWxHei8wUU5qs-zsJwXoLT-_g6R08vYVXWj7_v8G_hgMt9gfEv5hH</recordid><startdate>20090901</startdate><enddate>20090901</enddate><creator>Dasarathy, Srinivasan</creator><creator>Kasumov, Takhar</creator><creator>Edmison, John M</creator><creator>Gruca, Lourdes L</creator><creator>Bennett, Carole</creator><creator>Duenas, Clarita</creator><creator>Marczewski, Susan</creator><creator>McCullough, Arthur J</creator><creator>Hanson, Richard W</creator><creator>Kalhan, Satish C</creator><general>American Physiological Society</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>7X8</scope><scope>5PM</scope></search><sort><creationdate>20090901</creationdate><title>Glycine and urea kinetics in nonalcoholic steatohepatitis in human: effect of intralipid infusion</title><author>Dasarathy, Srinivasan ; Kasumov, Takhar ; Edmison, John M ; Gruca, Lourdes L ; Bennett, Carole ; Duenas, Clarita ; Marczewski, Susan ; McCullough, Arthur J ; Hanson, Richard W ; Kalhan, Satish C</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c487t-2869f1923f94d3a20af9bc5edf8bb738db6172098ad143206d72553efa68e89c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>3-Hydroxybutyric Acid - blood</topic><topic>Adult</topic><topic>Aged</topic><topic>Amino acids</topic><topic>Case-Control Studies</topic><topic>Cystathionine - blood</topic><topic>Fasting - blood</topic><topic>Fat Emulsions, Intravenous - administration & dosage</topic><topic>Fat Emulsions, Intravenous - metabolism</topic><topic>Fatty acids</topic><topic>Fatty Acids, Nonesterified - blood</topic><topic>Fatty Liver - metabolism</topic><topic>Female</topic><topic>Glutathione - blood</topic><topic>Glycine - blood</topic><topic>Humans</topic><topic>Infusions, Intravenous</topic><topic>Kinetics</topic><topic>Liver - metabolism</topic><topic>Liver and Biliary Tract</topic><topic>Liver diseases</topic><topic>Male</topic><topic>Metabolism</topic><topic>Middle Aged</topic><topic>Oxidation</topic><topic>Oxidation-Reduction</topic><topic>Oxidative Stress</topic><topic>Postprandial Period</topic><topic>Protein synthesis</topic><topic>Serine - blood</topic><topic>Urea - blood</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Dasarathy, Srinivasan</creatorcontrib><creatorcontrib>Kasumov, Takhar</creatorcontrib><creatorcontrib>Edmison, John M</creatorcontrib><creatorcontrib>Gruca, Lourdes L</creatorcontrib><creatorcontrib>Bennett, Carole</creatorcontrib><creatorcontrib>Duenas, Clarita</creatorcontrib><creatorcontrib>Marczewski, Susan</creatorcontrib><creatorcontrib>McCullough, Arthur J</creatorcontrib><creatorcontrib>Hanson, Richard W</creatorcontrib><creatorcontrib>Kalhan, Satish C</creatorcontrib><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>PubMed Central (Full Participant titles)</collection><jtitle>American journal of physiology: Gastrointestinal and liver physiology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Dasarathy, Srinivasan</au><au>Kasumov, Takhar</au><au>Edmison, John M</au><au>Gruca, Lourdes L</au><au>Bennett, Carole</au><au>Duenas, Clarita</au><au>Marczewski, Susan</au><au>McCullough, Arthur J</au><au>Hanson, Richard W</au><au>Kalhan, Satish C</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Glycine and urea kinetics in nonalcoholic steatohepatitis in human: effect of intralipid infusion</atitle><jtitle>American journal of physiology: Gastrointestinal and liver physiology</jtitle><addtitle>Am J Physiol Gastrointest Liver Physiol</addtitle><date>2009-09-01</date><risdate>2009</risdate><volume>297</volume><issue>3</issue><spage>G567</spage><epage>G575</epage><pages>G567-G575</pages><issn>0193-1857</issn><eissn>1522-1547</eissn><coden>APGPDF</coden><abstract>The rates of oxidation of glycine and ureagenesis were quantified in the basal state and in response to an intravenous infusion of intralipid with heparin (IL) in healthy subjects (n = 8) and in subjects with nonalcoholic steatohepatitis (NASH) (n = 6). During fasting, no significant difference in weight-specific rate of appearance (R(a)) of glycine, glycine oxidation, and urea synthesis was observed. Intralipid infusion resulted in a significant increase in plasma beta-hydroxybutyrate in both groups. The correlation between free fatty acids and beta-hydroxybutyrate concentration in plasma was 0.94 in NASH compared with 0.4 in controls, indicating greater hepatic fatty acid oxidation in NASH. Intralipid infusion resulted in a significant decrease in urea synthesis and glycine R(a) in both groups and did not impact glycine oxidation. The fractional contribution of glycine carbon to serine was lower in subjects with NASH before and after IL infusion. In contrast, the fractional contribution of serine carbon to cystathionine was higher in NASH before and following IL infusion. These results suggest that hepatic fatty acid oxidation is higher in NASH compared with controls and that glycine oxidation and urea synthesis are not altered. An increase in oxidative stress, induced by a higher rate of fatty acid oxidation in NASH, may have caused an increase in the contribution of serine to cystathionine to meet the higher demands for glutathione.</abstract><cop>United States</cop><pub>American Physiological Society</pub><pmid>19571235</pmid><doi>10.1152/ajpgi.00042.2009</doi><oa>free_for_read</oa></addata></record> |
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subjects | 3-Hydroxybutyric Acid - blood Adult Aged Amino acids Case-Control Studies Cystathionine - blood Fasting - blood Fat Emulsions, Intravenous - administration & dosage Fat Emulsions, Intravenous - metabolism Fatty acids Fatty Acids, Nonesterified - blood Fatty Liver - metabolism Female Glutathione - blood Glycine - blood Humans Infusions, Intravenous Kinetics Liver - metabolism Liver and Biliary Tract Liver diseases Male Metabolism Middle Aged Oxidation Oxidation-Reduction Oxidative Stress Postprandial Period Protein synthesis Serine - blood Urea - blood Young Adult |
title | Glycine and urea kinetics in nonalcoholic steatohepatitis in human: effect of intralipid infusion |
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