Journal article
Arteriovenous metabolomics in pigs reveals CFTR regulation of metabolism in multiple organs
The Journal of clinical investigation, Vol.134(13), e174500
07/01/2024
DOI: 10.1172/JCI174500
PMCID: PMC11213515
PMID: 38743489
Abstract
Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene cause cystic fibrosis (CF), a multiorgan disease that exhibits diverse metabolic defects. However, other than specific CFTR mutations, the factors that influence disease progression and severity remain poorly understood. Aberrant metabolite levels have been reported, but whether CFTR loss itself or secondary abnormalities (infection, inflammation, malnutrition, and various treatments) drive metabolic defects are uncertain. Here, we implemented comprehensive arteriovenous metabolomics in newborn CF pigs, and the results revealed CFTR as a bona fide regulator of metabolism. CFTR loss impaired metabolite exchange across organs, including disrupted lung uptake of fatty acids yet enhanced uptake of arachidonic acid, a precursor of pro-inflammatory cytokines. CFTR loss also impaired kidney reabsorption of amino acids and lactate and abolished renal glucose homeostasis. These and additional unexpected metabolic defects prior to disease manifestations reveal a fundamental role for CFTR in controlling multi-organ metabolism. Such discovery informs a basic understanding of CF, provides a foundation for future investigation, and has implications for developing therapies targeting only a single tissue.
Details
- Title: Subtitle
- Arteriovenous metabolomics in pigs reveals CFTR regulation of metabolism in multiple organs
- Creators
- Hosung Bae - University of California, IrvineBo Ram Kim - University of IowaSunhee Jung - University of California, IrvineJohnny Le - University of California, IrvineDana M van der Heide - University of IowaWenjie Yu - University of IowaSang Hee Park - University of California, IrvineBrieanna M Hilkin - University of IowaNicholas D Gansemer - University of IowaLinda S Powers - University of IowaTaekyung Kang - University of California, IrvineDavid K Meyerholz - University of IowaVictor L Schuster - Albert Einstein College of MedicineCholsoon Jang - University of California, IrvineMichael J Welsh - University of Iowa
- Resource Type
- Journal article
- Publication Details
- The Journal of clinical investigation, Vol.134(13), e174500
- DOI
- 10.1172/JCI174500
- PMID
- 38743489
- PMCID
- PMC11213515
- NLM abbreviation
- J Clin Invest
- eISSN
- 1558-8238
- Language
- English
- Electronic publication date
- 05/14/2024
- Date published
- 07/01/2024
- Academic Unit
- Neurology; Molecular Physiology and Biophysics; Pulmonary, Critical Care, and Occupational Medicine; Pathology; Fraternal Order of Eagles Diabetes Research Center; Neurosurgery; Internal Medicine
- Record Identifier
- 9984626999002771
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