TY - JOUR
T1 - Dietary fat composition shapes bile acid metabolism and severity of liver injury in a pig model of pediatric NAFLD
AU - Manjarín, Rodrigo
AU - Dillard, Kayla
AU - Coffin, Morgan
AU - Hernandez, Gabriella V.
AU - Smith, Victoria A.
AU - Noland-Lidell, Trista
AU - Gehani, Tanvi R.
AU - Smart, Hayden J.
AU - Wheeler, Kevin
AU - Sprayberry, Kimberly A.
AU - Edwards, Mark S.
AU - Fanter, Rob K.
AU - Glanz, Hunter
AU - Immoos, Chad
AU - Santiago-Rodriguez, Tasha M.
AU - Blank, Jason M.
AU - Burrin, Douglas G.
AU - Piccolo, Brian D.
AU - Abo-Ismail, Mohammed
AU - La Frano, Michael R.
AU - Maj, Magdalena
N1 - Funding Information:
This work was supported by California State University Agriculture Research Institute (Grants 58873 and 58913), California Polytechnic State University internal funding programs Baker/Koob,
Funding Information:
RSCA, Hull Graduate Assistantship and STRIDE, the USDA, Agricultural Research Service Grants 3092–51000-060-01 and 6026–51000-012-06S, grants from the National Institutes of Health Grant DK-094616, and the Texas Medical Center Digestive Diseases Center (NIH Grant P30 DK-56338), BiOWiSH Technologies, Hilmar Ingredients, and Acorn Seekers.
Publisher Copyright:
© 2022 the American Physiological Society.
PY - 2022/9
Y1 - 2022/9
N2 - The objective of this study was to investigate the effect of dietary fatty acid (FA) composition on bile acid (BA) metabolism in a pig model of NAFLD, by using a multiomics approach combined with histology and serum biochemistry. Thirty 20-dayold Iberian pigs pair-housed in pens were randomly assigned to receive 1 of 3 hypercaloric diets for 10 wk: 1) lard-enriched (LAR; n = 5 pens), 2) olive oil-enriched (OLI; n = 5), and 3) coconut oil-enriched (COC; n = 5). Animals were euthanized on week 10 after blood sampling, and liver, colon, and distal ileum (DI) were collected for histology, metabolomics, and transcriptomics. Data were analyzed by multivariate and univariate statistics. Compared with OLI and LAR, COC increased primary and secondary BAs in liver, plasma, and colon. In addition, both COC and OLI reduced circulating fibroblast growth factor 19, increased hepatic necrosis, composite lesion score, and liver enzymes in serum, and upregulated genes involved in hepatocyte proliferation and DNA repair. The severity of liver disease in COC and OLI pigs was associated with increased levels of phosphatidylcholines, medium-chain triacylglycerides, trimethylamine-N-oxide, and long-chain acylcarnitines in the liver, and the expression of profibrotic markers in DI, but not with changes in the composition or size of BA pool. In conclusion, our results indicate a role of dietary FAs in the regulation of BA metabolism and progression of NAFLD. Interventions that aim to modify the composition of dietary FAs, rather than to regulate BA metabolism or signaling, may be more effective in the treatment of NAFLD.
AB - The objective of this study was to investigate the effect of dietary fatty acid (FA) composition on bile acid (BA) metabolism in a pig model of NAFLD, by using a multiomics approach combined with histology and serum biochemistry. Thirty 20-dayold Iberian pigs pair-housed in pens were randomly assigned to receive 1 of 3 hypercaloric diets for 10 wk: 1) lard-enriched (LAR; n = 5 pens), 2) olive oil-enriched (OLI; n = 5), and 3) coconut oil-enriched (COC; n = 5). Animals were euthanized on week 10 after blood sampling, and liver, colon, and distal ileum (DI) were collected for histology, metabolomics, and transcriptomics. Data were analyzed by multivariate and univariate statistics. Compared with OLI and LAR, COC increased primary and secondary BAs in liver, plasma, and colon. In addition, both COC and OLI reduced circulating fibroblast growth factor 19, increased hepatic necrosis, composite lesion score, and liver enzymes in serum, and upregulated genes involved in hepatocyte proliferation and DNA repair. The severity of liver disease in COC and OLI pigs was associated with increased levels of phosphatidylcholines, medium-chain triacylglycerides, trimethylamine-N-oxide, and long-chain acylcarnitines in the liver, and the expression of profibrotic markers in DI, but not with changes in the composition or size of BA pool. In conclusion, our results indicate a role of dietary FAs in the regulation of BA metabolism and progression of NAFLD. Interventions that aim to modify the composition of dietary FAs, rather than to regulate BA metabolism or signaling, may be more effective in the treatment of NAFLD.
KW - Iberian pig
KW - lipidomics
KW - NASH
KW - pediatric model
KW - transcriptomics
UR - http://www.scopus.com/inward/record.url?scp=85136686585&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85136686585&partnerID=8YFLogxK
U2 - 10.1152/ajpendo.00052.2022
DO - 10.1152/ajpendo.00052.2022
M3 - Article
C2 - 35858244
AN - SCOPUS:85136686585
SN - 0193-1849
VL - 323
SP - E187-E206
JO - American Journal of Physiology - Endocrinology and Metabolism
JF - American Journal of Physiology - Endocrinology and Metabolism
IS - 3
ER -