Infection decreases fatty acid oxidation and nuclear hormone receptors in the diaphragm
Open accessAbstract
Respiratory failure is a major cause of mortality during septic shock and is due in part to decreased ventilatory muscle contraction. Ventilatory muscles have high energy demands; fatty acid (FA) oxidation is an important source of ATP. FA oxidation is regulated by nuclear hormone receptors; studies have shown that the expression of these receptors is decreased in liver, heart, and kidney during sepsis. Here, we demonstrate that lipopolysaccharide (LPS) decreases FA oxidation and the expression of lipoprotein lipase (LPL), FA transport protein 1 (FATP-1), CD36, carnitine palmitoyltransferase beta, medium chain acyl-CoA dehydrogenase (MCAD), and acyl-CoA synthetase, key proteins required for FA uptake and oxidation, in the diaphragm. LPS also decreased mRNA levels of PPARalpha and beta/delta, RXRalpha, beta, and gamma, thyroid hormone receptor alpha and beta, and estrogen related receptor alpha (ERRalpha) and their coactivators PGC-1alpha, PGC-1beta, SRC1, SRC2, Lipin 1, and CBP. Zymosan resulted in similar changes in the diaphragm. Finally, in PPARalpha deficient mice, baseline CPT-1beta and FATP-1 levels were markedly decreased and were not further reduced by LPS suggesting that a decrease in the PPARalpha signaling pathway plays an important role in inducing some of these changes. The decrease in FA oxidation in the diaphragm may be detrimental, leading to decreased diaphragm contraction and an increased risk of respiratory failure during sepsis.
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Acute inflammation profoundly decreases TRα1 and TRβ1 mRNA expression in the mouse diaphragm in association with decreased expression of co-activators involved in nuclear receptor activation.
“Acute inflammation profoundly decreases TRα1 and TRβ1 mRNA expression in the mouse diaphragm in association with decreased expression of co-activators involved in nuclear receptor activation [47].”
From An update on non-thyroidal illness syndrome (2021) · cites this paper as [47]
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- Authors
- Feingold, K. R., Moser, A., Patzek, S. M., Shigenaga, J. K., & Grunfeld, C.
- Affiliations
- San Francisco VA Medical Center (US)
- Corresponding author
- Feingold, Kenneth R.
- ORCID
- Patzek, Sophie M.
- Venue
- Journal of Lipid Research
- Publisher
- Elsevier BV
- Published
- 2009-10
- Volume
- 50
- Issue
- 10
- Pages
- 2055-2063
- ISSN
- 0022-2275 (ISSN-L)
- PMC
- PMC2739760
- OpenAlex
- W2136815314
- Cited by
- 59
- References
- 39
- Citations by year
- 2026: 1 · 2024: 3 · 2023: 2 · 2021: 2 · 2020: 4 · 2019: 3 · 2018: 4 · 2017: 2 · 2016: 5 · 2015: 4 · 2014: 7 · 2013: 6 · 2012: 7
- FWCI
- 2.15
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Lipid Research (publishedVersion, cc-by)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR049932)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Health Sciences › Medicine › Epidemiology › Sepsis Diagnosis and Treatment
- Keywords
- fatty acid oxidation, diaphragm, sepsis, lipopolysaccharide, zymosan, nuclear receptors, PPARα, respiratory failure, CD36, acyl-CoA synthetase, medium-chain acyl-CoA dehydrogenase, PGC-1α, transcriptional coactivator, energy metabolism
- MeSH terms
- Animals, Diaphragm, Fatty Acids, Female, Lipopolysaccharides, Mice, Inbred C57BL, Oxidation-Reduction, Triglycerides, Blotting, Western, Polymerase Chain Reaction, Receptors, Cytoplasmic and Nuclear, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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