Dietary fat composition shapes bile acid metabolism and severity of liver injury in a pig model of pediatric NAFLD

Rodrigo Manjarín, Kayla Dillard, Morgan Coffin, Gabriella V. Hernandez, Victoria A. Smith, Trista Noland-Lidell, Tanvi R. Gehani, Hayden J. Smart, Kevin Wheeler, Kimberly A. Sprayberry, Mark S. Edwards, Rob K. Fanter, Hunter Glanz, Chad Immoos, Tasha M. Santiago-Rodriguez, Jason M. Blank, Douglas G. Burrin, Brian D. Piccolo, Mohammed Abo-Ismail, Michael R. La FranoMagdalena Maj

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)E187-E206
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume323
Issue number3
DOIs
StatePublished - Sep 2022
Externally publishedYes

Keywords

  • Iberian pig
  • lipidomics
  • NASH
  • pediatric model
  • transcriptomics

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Physiology (medical)

Fingerprint

Dive into the research topics of 'Dietary fat composition shapes bile acid metabolism and severity of liver injury in a pig model of pediatric NAFLD'. Together they form a unique fingerprint.

Cite this