Downregulation of PGC-1α Prevents the Beneficial Effect of EET-Heme Oxygenase-1 on Mitochondrial Integrity and Associated Metabolic Function in Obese Mice
Joint Authors
Cao, Jian
Abraham, Nader G.
Singh, Shailendra P.
Falck, John R.
Kappas, Attallah
Vanella, Luca
Bellner, Lars
Source
Journal of Nutrition and Metabolism
Issue
Vol. 2016, Issue 2016 (31 Dec. 2016), pp.1-15, 15 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2016-12-20
Country of Publication
Egypt
No. of Pages
15
Main Subjects
Abstract EN
Background/Objectives.
Obesity and metabolic syndrome and associated adiposity are a systemic condition characterized by increased mitochondrial dysfunction, inflammation, and inhibition of antioxidant genes, HO-1, and EETs levels.
We postulate that EETs attenuate adiposity by stimulating mitochondrial function and induction of HO-1 via activation of PGC-1α in adipose and hepatic tissue.
Methods.
Cultured murine adipocytes and mice fed a high fat (HF) diet were used to assess the functional relationship among EETs, PGC-1α, HO-1, and mitochondrial signaling using an EET-agonist (EET-A) and PGC-1α-deficient cells and mice using lentiviral PGC-1α(sh).
Results.
EET-A is a potent inducer of PGC-1α, HO-1, mitochondrial biogenesis (cytochrome oxidase subunits 1 and 4 and SIRT3), fusion proteins (Mfn 1/2 and OPA1) and fission proteins (DRP1 and FIS1) (p<0.05), fasting glucose, BW, and blood pressure.
These beneficial effects were prevented by administration of lenti-PGC-1α(sh).
EET-A administration prevented HF diet induced mitochondrial and dysfunction in adipose tissue and restored VO2 effects that were abrogated in PGC-1α-deficient mice.
Conclusion.
EET is identified as an upstream positive regulator of PGC-1α that leads to increased HO-1, decreased BW and fasting blood glucose and increased insulin receptor phosphorylation, that is, increased insulin sensitivity and mitochondrial integrity, and possible use of EET-agonist for treatment of obesity and metabolic syndrome.
American Psychological Association (APA)
Singh, Shailendra P.& Bellner, Lars& Vanella, Luca& Cao, Jian& Falck, John R.& Kappas, Attallah…[et al.]. 2016. Downregulation of PGC-1α Prevents the Beneficial Effect of EET-Heme Oxygenase-1 on Mitochondrial Integrity and Associated Metabolic Function in Obese Mice. Journal of Nutrition and Metabolism،Vol. 2016, no. 2016, pp.1-15.
https://search.emarefa.net/detail/BIM-1109617
Modern Language Association (MLA)
Singh, Shailendra P.…[et al.]. Downregulation of PGC-1α Prevents the Beneficial Effect of EET-Heme Oxygenase-1 on Mitochondrial Integrity and Associated Metabolic Function in Obese Mice. Journal of Nutrition and Metabolism No. 2016 (2016), pp.1-15.
https://search.emarefa.net/detail/BIM-1109617
American Medical Association (AMA)
Singh, Shailendra P.& Bellner, Lars& Vanella, Luca& Cao, Jian& Falck, John R.& Kappas, Attallah…[et al.]. Downregulation of PGC-1α Prevents the Beneficial Effect of EET-Heme Oxygenase-1 on Mitochondrial Integrity and Associated Metabolic Function in Obese Mice. Journal of Nutrition and Metabolism. 2016. Vol. 2016, no. 2016, pp.1-15.
https://search.emarefa.net/detail/BIM-1109617
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1109617