Validation of an omega-3 substrate challenge absorption test as an indicator of global fat lipolysis
Freedman, Steven D. ; Zaworski, Kamil ; Pierzynowska, Kateryna LU
; Pierzynowski, Stefan
LU
; Gallotto, Robert
; Sathe, Meghana
and Borowitz, Drucy S.
(2023)
In PLoS ONE
18(5 MAY).
- Abstract
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... (More)
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 Tmax 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.
(Less)
- author
- Freedman, Steven D.
; Zaworski, Kamil
; Pierzynowska, Kateryna
LU
; Pierzynowski, Stefan
LU
; Gallotto, Robert
; Sathe, Meghana
and Borowitz, Drucy S.
- organization
- publishing date
- 2023-05
- type
- Contribution to journal
- publication status
- published
- subject
- in
- PLoS ONE
- volume
- 18
- issue
- 5 MAY
- article number
- e0284651
- publisher
- Public Library of Science (PLoS)
- external identifiers
-
- pmid:37155649
- scopus:85158137038
- ISSN
- 1932-6203
- DOI
- 10.1371/journal.pone.0284651
- language
- English
- LU publication?
- yes
- id
- 4bd41a75-20f3-436e-bd0f-633ee1fb6dd5
- date added to LUP
- 2023-08-16 08:33:37
- date last changed
- 2024-04-20 00:43:01
@article{4bd41a75-20f3-436e-bd0f-633ee1fb6dd5,
abstract = {{<p>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<sub>max</sub> 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.</p>}},
author = {{Freedman, Steven D. and Zaworski, Kamil and Pierzynowska, Kateryna and Pierzynowski, Stefan and Gallotto, Robert and Sathe, Meghana and Borowitz, Drucy S.}},
issn = {{1932-6203}},
language = {{eng}},
number = {{5 MAY}},
publisher = {{Public Library of Science (PLoS)}},
series = {{PLoS ONE}},
title = {{Validation of an omega-3 substrate challenge absorption test as an indicator of global fat lipolysis}},
url = {{http://dx.doi.org/10.1371/journal.pone.0284651}},
doi = {{10.1371/journal.pone.0284651}},
volume = {{18}},
year = {{2023}},
}