Changes in Essential Fatty Acids and Ileal Genes Associated with Metabolizing Enzymes and Fatty Acid Transporters in Rodent Models of Cystic Fibrosis

Nirajan Shrestha; Nathan Rout-Pitt; Alexandra McCarron; Courtney A Jackson; Andrew C Bulmer; Andrew J McAinch; Martin Donnelley; David W Parsons; Deanne H Hryciw

doi:10.3390/ijms24087194

Changes in Essential Fatty Acids and Ileal Genes Associated with Metabolizing Enzymes and Fatty Acid Transporters in Rodent Models of Cystic Fibrosis

Int J Mol Sci. 2023 Apr 13;24(8):7194. doi: 10.3390/ijms24087194.

Authors

Nirajan Shrestha¹, Nathan Rout-Pitt^{2

3

4}, Alexandra McCarron^{2

3

4}, Courtney A Jackson⁵, Andrew C Bulmer¹, Andrew J McAinch^{6

7}, Martin Donnelley^{3

4

5}, David W Parsons^{3

4

5}, Deanne H Hryciw^{5

6

8}

Affiliations

¹ School of Pharmacy and Medical Sciences, Griffith University, Southport, QLD 4215, Australia.
² Robinson Research Institute, University of Adelaide, Adelaide, SA 5005, Australia.
³ Adelaide Medical School, University of Adelaide, Adelaide, SA 5001, Australia.
⁴ Respiratory and Sleep Medicine, Women's and Children's Hospital, 72 King William Road, North Adelaide, SA 5006, Australia.
⁵ School of Environment and Science, Griffith University, Nathan, QLD 4215, Australia.
⁶ Institute for Health and Sport, Victoria University, Melbourne, VIC 3000, Australia.
⁷ Australian Institute for Musculoskeletal Science (AIMSS), Victoria University, St. Albans, VIC 3021, Australia.
⁸ Griffith Institute for Drug Discovery, Griffith University, Nathan, QLD 4111, Australia.

Abstract

Cystic fibrosis (CF), the result of mutations in the CF transmembrane conductance regulator (CFTR), causes essential fatty acid deficiency. The aim of this study was to characterize fatty acid handling in two rodent models of CF; one strain which harbors the loss of phenylalanine at position 508 (Phe508del) in CFTR and the other lacks functional CFTR (510X). Fatty acid concentrations were determined using gas chromatography in serum from Phe508del and 510X rats. The relative expression of genes responsible for fatty acid transport and metabolism were quantified using real-time PCR. Ileal tissue morphology was assessed histologically. There was an age-dependent decrease in eicosapentaenoic acid and the linoleic acid:α-linolenic acid ratio, a genotype-dependent decrease in docosapentaenoic acid (n-3) and an increase in the arachidonic acid:docosahexaenoic acid ratio in Phe508del rat serum, which was not observed in 510X rats. In the ileum, Cftr mRNA was increased in Phe508del rats but decreased in 510X rats. Further, Elvol2, Slc27a1, Slc27a2 and Got2 mRNA were increased in Phe508del rats only. As assessed by Sirius Red staining, collagen was increased in Phe508del and 510X ileum. Thus, CF rat models exhibit alterations in the concentration of circulating fatty acids, which may be due to altered transport and metabolism, in addition to fibrosis and microscopic structural changes in the ileum.

Keywords: cystic fibrosis; fatty acids; intestine.

MeSH terms

Animals
Coenzyme A Ligases / metabolism
Cystic Fibrosis Transmembrane Conductance Regulator / genetics
Cystic Fibrosis Transmembrane Conductance Regulator / metabolism
Cystic Fibrosis* / metabolism
Fatty Acids, Essential
Genotype
Rats
Rodentia / metabolism

Substances

Cystic Fibrosis Transmembrane Conductance Regulator
Fatty Acids, Essential
Slc27a2 protein, rat
Coenzyme A Ligases

Grants and funding

DP and MD have received funding from National Health and Medical Research Council (GNT1160011) and the USA Cystic Fibrosis Foundation (PARSON18GO and DONNEL21GO).