The role of adipose and muscle tissue breakdown on interorgan energy substrate fluxes in a Pseudomonas aeruginosa induced sepsis model in female pigs

Abstract Sepsis leads to an acute breakdown of muscle to support increased caloric and amino acid requirements. Little is known about the role of adipose and muscle tissue breakdown and intestinal metabolism in glucose substrate supply during the acute phase of sepsis. In a translational porcine mod...

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Main Authors: Ryan Morse, Gabriella A. M. Ten Have, John J. Thaden, Marielle P. K. J. Engelen, Sarah Rice, Martin Hagve, Nicolaas E. P. Deutz
Format: Article
Language:English
Published: Wiley 2025-01-01
Series:Physiological Reports
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Online Access:https://doi.org/10.14814/phy2.70129
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author Ryan Morse
Gabriella A. M. Ten Have
John J. Thaden
Marielle P. K. J. Engelen
Sarah Rice
Martin Hagve
Nicolaas E. P. Deutz
author_facet Ryan Morse
Gabriella A. M. Ten Have
John J. Thaden
Marielle P. K. J. Engelen
Sarah Rice
Martin Hagve
Nicolaas E. P. Deutz
author_sort Ryan Morse
collection DOAJ
description Abstract Sepsis leads to an acute breakdown of muscle to support increased caloric and amino acid requirements. Little is known about the role of adipose and muscle tissue breakdown and intestinal metabolism in glucose substrate supply during the acute phase of sepsis. In a translational porcine model of sepsis, we explored the across organ net fluxes of gluconeogenic substrates. In 13 pigs, acute sepsis was induced by IV infusion of Pseudomonas aeruginosa, while in 9 pigs saline (control) was given for 18 h. Blood samples were collected between 12 and 18 h and analyzed with HPLC and LCMS. In sepsis, glucose plasma concentration was reduced (p = 0.0028). A concordant increase in splanchnic area net release of glucose (p = 0.0049), due to reduced uptake in the portal drained viscera (PDV) (p = 0.0032) with an unchanged liver production (p = 0.7861). The hindquarter showed a higher release of alanine (p = 0.0002), glutamine (p = 0.003), and lactate (p = 0.0007), but not for glycerol (p = 0.5718). Diminished PDV uptake of gluconeogenic amino acids, increased liver uptake of these substrates (p < 0.05), while no change in liver glycerol uptake (p = 0.3170), did not lead to an increased net liver glucose release. In the acute phase of sepsis, we hypothesize an important role of altered intestinal amino acid metabolism and breakdown of muscle proteins, but not of glycolysis to support gluconeogenesis.
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spelling doaj-art-95a6d3dc2f09485a9ac4c934aa5ece662025-01-15T13:36:31ZengWileyPhysiological Reports2051-817X2025-01-01131n/an/a10.14814/phy2.70129The role of adipose and muscle tissue breakdown on interorgan energy substrate fluxes in a Pseudomonas aeruginosa induced sepsis model in female pigsRyan Morse0Gabriella A. M. Ten Have1John J. Thaden2Marielle P. K. J. Engelen3Sarah Rice4Martin Hagve5Nicolaas E. P. Deutz6Center for Translational Research in Aging and Longevity, Department of Health and Kinesiology Texas A&M University College Station Texas USACenter for Translational Research in Aging and Longevity, Department of Health and Kinesiology Texas A&M University College Station Texas USACenter for Translational Research in Aging and Longevity, Department of Health and Kinesiology Texas A&M University College Station Texas USACenter for Translational Research in Aging and Longevity, Department of Health and Kinesiology Texas A&M University College Station Texas USACenter for Translational Research in Aging and Longevity, Department of Health and Kinesiology Texas A&M University College Station Texas USADepartment of Gastrointestinal Surgery University Hospital North‐Norway Tromso NorwayCenter for Translational Research in Aging and Longevity, Department of Health and Kinesiology Texas A&M University College Station Texas USAAbstract Sepsis leads to an acute breakdown of muscle to support increased caloric and amino acid requirements. Little is known about the role of adipose and muscle tissue breakdown and intestinal metabolism in glucose substrate supply during the acute phase of sepsis. In a translational porcine model of sepsis, we explored the across organ net fluxes of gluconeogenic substrates. In 13 pigs, acute sepsis was induced by IV infusion of Pseudomonas aeruginosa, while in 9 pigs saline (control) was given for 18 h. Blood samples were collected between 12 and 18 h and analyzed with HPLC and LCMS. In sepsis, glucose plasma concentration was reduced (p = 0.0028). A concordant increase in splanchnic area net release of glucose (p = 0.0049), due to reduced uptake in the portal drained viscera (PDV) (p = 0.0032) with an unchanged liver production (p = 0.7861). The hindquarter showed a higher release of alanine (p = 0.0002), glutamine (p = 0.003), and lactate (p = 0.0007), but not for glycerol (p = 0.5718). Diminished PDV uptake of gluconeogenic amino acids, increased liver uptake of these substrates (p < 0.05), while no change in liver glycerol uptake (p = 0.3170), did not lead to an increased net liver glucose release. In the acute phase of sepsis, we hypothesize an important role of altered intestinal amino acid metabolism and breakdown of muscle proteins, but not of glycolysis to support gluconeogenesis.https://doi.org/10.14814/phy2.70129amino acid metabolismgluconeogenesisglucoselipid metabolismpigsepsis
spellingShingle Ryan Morse
Gabriella A. M. Ten Have
John J. Thaden
Marielle P. K. J. Engelen
Sarah Rice
Martin Hagve
Nicolaas E. P. Deutz
The role of adipose and muscle tissue breakdown on interorgan energy substrate fluxes in a Pseudomonas aeruginosa induced sepsis model in female pigs
Physiological Reports
amino acid metabolism
gluconeogenesis
glucose
lipid metabolism
pig
sepsis
title The role of adipose and muscle tissue breakdown on interorgan energy substrate fluxes in a Pseudomonas aeruginosa induced sepsis model in female pigs
title_full The role of adipose and muscle tissue breakdown on interorgan energy substrate fluxes in a Pseudomonas aeruginosa induced sepsis model in female pigs
title_fullStr The role of adipose and muscle tissue breakdown on interorgan energy substrate fluxes in a Pseudomonas aeruginosa induced sepsis model in female pigs
title_full_unstemmed The role of adipose and muscle tissue breakdown on interorgan energy substrate fluxes in a Pseudomonas aeruginosa induced sepsis model in female pigs
title_short The role of adipose and muscle tissue breakdown on interorgan energy substrate fluxes in a Pseudomonas aeruginosa induced sepsis model in female pigs
title_sort role of adipose and muscle tissue breakdown on interorgan energy substrate fluxes in a pseudomonas aeruginosa induced sepsis model in female pigs
topic amino acid metabolism
gluconeogenesis
glucose
lipid metabolism
pig
sepsis
url https://doi.org/10.14814/phy2.70129
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