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Validation of an omega-3 substrate challenge absorption test as an indicator of global fat lipolysis

INTRODUCTION: The coefficient of fat absorption (CFA) quantifies fat that remains in stool after digestion and is not a direct measure of lipolysis. CFA has been used to assess treatment of pancreatic insufficiency but does not correlate with pancreatic enzyme replacement therapy dose. We explored u...

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Autores principales: Freedman, Steven D., Zaworski, Kamil, Pierzynowska, Kateryna, Pierzynowski, Stefan, Gallotto, Robert, Sathe, Meghana, Borowitz, Drucy S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10166528/
https://www.ncbi.nlm.nih.gov/pubmed/37155649
http://dx.doi.org/10.1371/journal.pone.0284651
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author Freedman, Steven D.
Zaworski, Kamil
Pierzynowska, Kateryna
Pierzynowski, Stefan
Gallotto, Robert
Sathe, Meghana
Borowitz, Drucy S.
author_facet Freedman, Steven D.
Zaworski, Kamil
Pierzynowska, Kateryna
Pierzynowski, Stefan
Gallotto, Robert
Sathe, Meghana
Borowitz, Drucy S.
author_sort Freedman, Steven D.
collection PubMed
description INTRODUCTION: The coefficient of fat absorption (CFA) quantifies fat that remains in stool after digestion and is not a direct measure of lipolysis. CFA has been used to assess treatment of pancreatic insufficiency but does not correlate with pancreatic enzyme replacement therapy dose. We explored use of an omega-3 substrate absorption challenge test as a sensitive test of lipolysis and absorption. METHODS: We studied a novel microbially-derived lipase (SNSP003) employing an established surgical model commonly used to study the uptake of macronutrients, the exocrine pancreatic insufficient pig. Pigs were fed a high-fat diet and given a standardized omega-3 substrate challenge to test the effect of lipolysis on its absorption. Blood was drawn at 0, 1, 2, 4, 6, 8, 12, and 24 hours following the substrate challenge and was analyzed for omega-3 and total fat levels (c14:c24). SNSP003 was also compard to porcine pancrelipase. RESULTS: The absorption of omega-3 fats was significantly increased following administration of 40, 80 and 120 mg SNSP003 lipase by 51% (p = 0.02), 89%, (p = 0.001) and 64% (p = 0.01), respectively, compared to that observed when no lipase was administered to the pigs, with T(max) at 4 hours. The two highest SNSP003 doses were compared to porcine pancrelipase and no significant differences were observed. Both doses increased plasma total fatty acids (141% for the 80 mg dose (p = 0.001) and 133% for the 120 mg dose (p = 0.006), compared to no lipase) and no significant differences were observed between the SNSP003 lipase doses and porcine pancrelipase. CONCLUSION: The omega-3 substrate absorption challenge test differentiates among different doses of a novel microbially-derived lipase and correlates with global fat lipolysis and absorption in exocrine pancreatic insufficient pigs. No significant differences were observed between the two highest novel lipase doses and porcine pancrelipase. Studies in humans should be designed to support the evidence presented here that suggests the omega-3 substrate absorption challenge test has advantages over the coefficient of fat absorption test to study lipase activity.
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spelling pubmed-101665282023-05-09 Validation of an omega-3 substrate challenge absorption test as an indicator of global fat lipolysis Freedman, Steven D. Zaworski, Kamil Pierzynowska, Kateryna Pierzynowski, Stefan Gallotto, Robert Sathe, Meghana Borowitz, Drucy S. PLoS One Research Article INTRODUCTION: The coefficient of fat absorption (CFA) quantifies fat that remains in stool after digestion and is not a direct measure of lipolysis. CFA has been used to assess treatment of pancreatic insufficiency but does not correlate with pancreatic enzyme replacement therapy dose. We explored use of an omega-3 substrate absorption challenge test as a sensitive test of lipolysis and absorption. METHODS: We studied a novel microbially-derived lipase (SNSP003) employing an established surgical model commonly used to study the uptake of macronutrients, the exocrine pancreatic insufficient pig. Pigs were fed a high-fat diet and given a standardized omega-3 substrate challenge to test the effect of lipolysis on its absorption. Blood was drawn at 0, 1, 2, 4, 6, 8, 12, and 24 hours following the substrate challenge and was analyzed for omega-3 and total fat levels (c14:c24). SNSP003 was also compard to porcine pancrelipase. RESULTS: The absorption of omega-3 fats was significantly increased following administration of 40, 80 and 120 mg SNSP003 lipase by 51% (p = 0.02), 89%, (p = 0.001) and 64% (p = 0.01), respectively, compared to that observed when no lipase was administered to the pigs, with T(max) at 4 hours. The two highest SNSP003 doses were compared to porcine pancrelipase and no significant differences were observed. Both doses increased plasma total fatty acids (141% for the 80 mg dose (p = 0.001) and 133% for the 120 mg dose (p = 0.006), compared to no lipase) and no significant differences were observed between the SNSP003 lipase doses and porcine pancrelipase. CONCLUSION: The omega-3 substrate absorption challenge test differentiates among different doses of a novel microbially-derived lipase and correlates with global fat lipolysis and absorption in exocrine pancreatic insufficient pigs. No significant differences were observed between the two highest novel lipase doses and porcine pancrelipase. Studies in humans should be designed to support the evidence presented here that suggests the omega-3 substrate absorption challenge test has advantages over the coefficient of fat absorption test to study lipase activity. Public Library of Science 2023-05-08 /pmc/articles/PMC10166528/ /pubmed/37155649 http://dx.doi.org/10.1371/journal.pone.0284651 Text en © 2023 Freedman et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Freedman, Steven D.
Zaworski, Kamil
Pierzynowska, Kateryna
Pierzynowski, Stefan
Gallotto, Robert
Sathe, Meghana
Borowitz, Drucy S.
Validation of an omega-3 substrate challenge absorption test as an indicator of global fat lipolysis
title Validation of an omega-3 substrate challenge absorption test as an indicator of global fat lipolysis
title_full Validation of an omega-3 substrate challenge absorption test as an indicator of global fat lipolysis
title_fullStr Validation of an omega-3 substrate challenge absorption test as an indicator of global fat lipolysis
title_full_unstemmed Validation of an omega-3 substrate challenge absorption test as an indicator of global fat lipolysis
title_short Validation of an omega-3 substrate challenge absorption test as an indicator of global fat lipolysis
title_sort validation of an omega-3 substrate challenge absorption test as an indicator of global fat lipolysis
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10166528/
https://www.ncbi.nlm.nih.gov/pubmed/37155649
http://dx.doi.org/10.1371/journal.pone.0284651
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