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Role for animal models in understanding essential fatty acid deficiency in cystic fibrosis

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Abstract

Essential fatty acid deficiency has been observed in most patients with Cystic Fibrosis (CF); however, pancreatic supplementation does not restore the deficiency, suggesting a different pathology independent of the pancreas. At this time, the underlying pathological mechanisms are largely unknown. Essential fatty acids are obtained from the diet and processed by organs including the liver and intestine, two organs significantly impacted by mutations in the cystic fibrosis transmembrane conductance regulator gene (Cftr). There are several CF animal models in a variety of species that have been developed to investigate molecular mechanisms associated with the CF phenotype. Specifically, global and systemic mutations in Cftr which mimic genotypic changes identified in CF patients have been generated in mice, rats, sheep, pigs and ferrets. These mutations produce CFTR proteins with a gating defect, trafficking defect, or an absent or inactive CFTR channel. Essential fatty acids are critical to CFTR function, with a bidirectional relationship between CFTR and essential fatty acids proposed. Currently, there are limited analyses on the essential fatty acid status in most of these animal models. Of interest, in the mouse model, essential fatty acid status is dependent on the genotype and resultant phenotype of the mouse. Future investigations should identify an optimal animal model that has most of the phenotypic changes associated with CF including the essential fatty acid deficiencies, which can be used in the development of therapeutics.

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Acknowledgements

The authors thank the contributions of members of the laboratories, who have contributed to current and past research on Cystic Fibrosis and essential fatty acid metabolism. Figures were produced using Biorender.

Funding

DP and MD: NHMRC (GNT1160011), and the CF Foundation (PARSON18G0).

Author information

Authors and Affiliations

  1. School of Environment and Science, Griffith University, Nathan, QLD, Australia

    Deanne H. Hryciw & Courtney A. Jackson

  2. Centre for Planetary Health and Food Security, Griffith University, Nathan, QLD, Australia

    Deanne H. Hryciw

  3. Institute for Health and Sport, Victoria University, Melbourne, VIC, Australia

    Deanne H. Hryciw & Andrew J. McAinch

  4. School of Pharmacy and Medical Sciences, Griffith University, Southport, QLD, Australia

    Nirajan Shrestha

  5. Adelaide Medical School, University of Adelaide, Adelaide, SA, Australia

    David Parsons & Martin Donnelley

  6. Respiratory and Sleep Medicine, Women’s and Children’s Hospital, North Adelaide, SA, Australia

    David Parsons & Martin Donnelley

  7. Robinson Research Institute, University of Adelaide, Adelaide, SA, Australia

    David Parsons & Martin Donnelley

  8. Australian Institute for Musculoskeletal Science (AIMSS), Victoria University, St. Albans, VIC, Australia

    Andrew J. McAinch

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  1. Deanne H. Hryciw
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  2. Courtney A. Jackson
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CJ and DH completed the first draft of the manuscript. All authors assisted with subsequent drafts and approved the final draft.

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Correspondence to Deanne H. Hryciw.

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Hryciw, D.H., Jackson, C.A., Shrestha, N. et al. Role for animal models in understanding essential fatty acid deficiency in cystic fibrosis. Cell. Mol. Life Sci. 78, 7991–7999 (2021). https://doi.org/10.1007/s00018-021-04014-2

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