Advertisement
ResearchIn-Press PreviewMetabolism Open Access | 10.1172/JCI174500
1Department of Biological Chemistry, University of California at Irvine, Irvine, United States of America
2Department of Internal Medicine, Pappajohn Biomedical Institute, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, United States of America
3Department of Surgery, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, United States of America
4Department of Pathology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, United States of America
5Department of Internal Medicine, Albert Einstein College of Medicine, New York, United States of America
Find articles by Bae, H. in: JCI | PubMed | Google Scholar |
1Department of Biological Chemistry, University of California at Irvine, Irvine, United States of America
2Department of Internal Medicine, Pappajohn Biomedical Institute, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, United States of America
3Department of Surgery, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, United States of America
4Department of Pathology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, United States of America
5Department of Internal Medicine, Albert Einstein College of Medicine, New York, United States of America
Find articles by Kim, B. in: JCI | PubMed | Google Scholar
1Department of Biological Chemistry, University of California at Irvine, Irvine, United States of America
2Department of Internal Medicine, Pappajohn Biomedical Institute, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, United States of America
3Department of Surgery, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, United States of America
4Department of Pathology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, United States of America
5Department of Internal Medicine, Albert Einstein College of Medicine, New York, United States of America
Find articles by Jung, S. in: JCI | PubMed | Google Scholar
1Department of Biological Chemistry, University of California at Irvine, Irvine, United States of America
2Department of Internal Medicine, Pappajohn Biomedical Institute, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, United States of America
3Department of Surgery, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, United States of America
4Department of Pathology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, United States of America
5Department of Internal Medicine, Albert Einstein College of Medicine, New York, United States of America
Find articles by Le, J. in: JCI | PubMed | Google Scholar |
1Department of Biological Chemistry, University of California at Irvine, Irvine, United States of America
2Department of Internal Medicine, Pappajohn Biomedical Institute, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, United States of America
3Department of Surgery, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, United States of America
4Department of Pathology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, United States of America
5Department of Internal Medicine, Albert Einstein College of Medicine, New York, United States of America
Find articles by van der Heide, D. in: JCI | PubMed | Google Scholar
1Department of Biological Chemistry, University of California at Irvine, Irvine, United States of America
2Department of Internal Medicine, Pappajohn Biomedical Institute, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, United States of America
3Department of Surgery, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, United States of America
4Department of Pathology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, United States of America
5Department of Internal Medicine, Albert Einstein College of Medicine, New York, United States of America
Find articles by Yu, W. in: JCI | PubMed | Google Scholar |
1Department of Biological Chemistry, University of California at Irvine, Irvine, United States of America
2Department of Internal Medicine, Pappajohn Biomedical Institute, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, United States of America
3Department of Surgery, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, United States of America
4Department of Pathology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, United States of America
5Department of Internal Medicine, Albert Einstein College of Medicine, New York, United States of America
Find articles by Park, S. in: JCI | PubMed | Google Scholar
1Department of Biological Chemistry, University of California at Irvine, Irvine, United States of America
2Department of Internal Medicine, Pappajohn Biomedical Institute, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, United States of America
3Department of Surgery, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, United States of America
4Department of Pathology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, United States of America
5Department of Internal Medicine, Albert Einstein College of Medicine, New York, United States of America
Find articles by Hilkin, B. in: JCI | PubMed | Google Scholar
1Department of Biological Chemistry, University of California at Irvine, Irvine, United States of America
2Department of Internal Medicine, Pappajohn Biomedical Institute, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, United States of America
3Department of Surgery, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, United States of America
4Department of Pathology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, United States of America
5Department of Internal Medicine, Albert Einstein College of Medicine, New York, United States of America
Find articles by Gansemer, N. in: JCI | PubMed | Google Scholar |
1Department of Biological Chemistry, University of California at Irvine, Irvine, United States of America
2Department of Internal Medicine, Pappajohn Biomedical Institute, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, United States of America
3Department of Surgery, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, United States of America
4Department of Pathology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, United States of America
5Department of Internal Medicine, Albert Einstein College of Medicine, New York, United States of America
Find articles by Powers, L. in: JCI | PubMed | Google Scholar
1Department of Biological Chemistry, University of California at Irvine, Irvine, United States of America
2Department of Internal Medicine, Pappajohn Biomedical Institute, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, United States of America
3Department of Surgery, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, United States of America
4Department of Pathology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, United States of America
5Department of Internal Medicine, Albert Einstein College of Medicine, New York, United States of America
Find articles by Kang, T. in: JCI | PubMed | Google Scholar
1Department of Biological Chemistry, University of California at Irvine, Irvine, United States of America
2Department of Internal Medicine, Pappajohn Biomedical Institute, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, United States of America
3Department of Surgery, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, United States of America
4Department of Pathology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, United States of America
5Department of Internal Medicine, Albert Einstein College of Medicine, New York, United States of America
Find articles by Meyerholz, D. in: JCI | PubMed | Google Scholar |
1Department of Biological Chemistry, University of California at Irvine, Irvine, United States of America
2Department of Internal Medicine, Pappajohn Biomedical Institute, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, United States of America
3Department of Surgery, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, United States of America
4Department of Pathology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, United States of America
5Department of Internal Medicine, Albert Einstein College of Medicine, New York, United States of America
Find articles by Schuster, V. in: JCI | PubMed | Google Scholar |
1Department of Biological Chemistry, University of California at Irvine, Irvine, United States of America
2Department of Internal Medicine, Pappajohn Biomedical Institute, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, United States of America
3Department of Surgery, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, United States of America
4Department of Pathology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, United States of America
5Department of Internal Medicine, Albert Einstein College of Medicine, New York, United States of America
Find articles by Jang, C. in: JCI | PubMed | Google Scholar |
1Department of Biological Chemistry, University of California at Irvine, Irvine, United States of America
2Department of Internal Medicine, Pappajohn Biomedical Institute, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, United States of America
3Department of Surgery, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, United States of America
4Department of Pathology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, United States of America
5Department of Internal Medicine, Albert Einstein College of Medicine, New York, United States of America
Find articles by Welsh, M. in: JCI | PubMed | Google Scholar |
Published May 14, 2024 - More info
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.