Oltipraz upregulates the nuclear factor (erythroid-derived 2)-like 2 [corrected](NRF2) antioxidant system and prevents insulin resistance and obesity induced by a high-fat diet in C57BL/6J mice
- PMID: 21161163
- DOI: 10.1007/s00125-010-2001-8
Oltipraz upregulates the nuclear factor (erythroid-derived 2)-like 2 [corrected](NRF2) antioxidant system and prevents insulin resistance and obesity induced by a high-fat diet in C57BL/6J mice
Erratum in
- Diabetologia. 2011 Apr;54(4):989
Abstract
Aims/hypothesis: We investigated whether oltipraz, a nuclear respiratory factor 2 alpha subunit (NRF2) activator, improves insulin sensitivity and prevents the development of obesity in mice.
Methods: C57BL/6J mice were fed with a low-fat diet (10% of energy as fat), a high-fat diet (HFD) (45% of energy as fat) or a HFD with oltipraz for 28 weeks. The effects of oltipraz on body weight, fat content, glucose disposal, insulin signalling, metabolic profiles and endogenous NRF2 functional status in the three groups of mice were investigated.
Results: Oltipraz prevented or significantly attenuated the effect of HFD on glucose disposal, body weight and fat gain. Impairment of protein kinase B/Akt phosphorylation in this HFD-fed mouse model in response to intraperitoneal insulin injection was observed in adipose tissue, but not in the muscles, accompanied by inhibition of AMP-activated protein kinase signalling and activation of p70S6 kinase, as well as reduced GLUT4 content. These defects were attenuated by oltipraz administration. Nuclear content of NRF2 in adipose tissue was reduced by HFD feeding, associated with increased Keap1 mRNA expression and reduced production of haem oxygenase-1 and superoxide dismutase, increased protein oxidation, decreased plasma reduced:oxidised glutathione ratio and the appearance of macrophage marker F4/80. These defects were also restored by oltipraz. Finally, oltipraz attenuated HFD-induced inducible nitric oxide synthase overproduction.
Conclusions/interpretation: Impairment of the endogenous redox system is important in the development of obesity and insulin resistance in chronic HFD feeding. NRF2 activation represents a potential novel approach in the treatment and prevention of obesity and diabetes.
Similar articles
-
Glucoraphanin: a broccoli sprout extract that ameliorates obesity-induced inflammation and insulin resistance.Adipocyte. 2018;7(3):218-225. doi: 10.1080/21623945.2018.1474669. Epub 2018 Aug 9. Adipocyte. 2018. PMID: 29898626 Free PMC article. Review.
-
Rosa Mosqueta Oil Prevents Oxidative Stress and Inflammation through the Upregulation of PPAR-α and NRF2 in C57BL/6J Mice Fed a High-Fat Diet.J Nutr. 2017 Apr;147(4):579-588. doi: 10.3945/jn.116.243261. Epub 2017 Mar 15. J Nutr. 2017. PMID: 28298541
-
Emerging role of Nrf2 in adipocytes and adipose biology.Adv Nutr. 2013 Jan 1;4(1):62-6. doi: 10.3945/an.112.003103. Adv Nutr. 2013. PMID: 23319124 Free PMC article. Review.
-
Enhanced Nrf2 activity worsens insulin resistance, impairs lipid accumulation in adipose tissue, and increases hepatic steatosis in leptin-deficient mice.Diabetes. 2012 Dec;61(12):3208-18. doi: 10.2337/db11-1716. Epub 2012 Aug 30. Diabetes. 2012. PMID: 22936178 Free PMC article.
-
Chronic blockade of nitric oxide synthesis reduces adiposity and improves insulin resistance in high fat-induced obese mice.Endocrinology. 2007 Oct;148(10):4548-56. doi: 10.1210/en.2006-1371. Epub 2007 Jun 21. Endocrinology. 2007. PMID: 17584959
Cited by
-
Nrf-2 as a novel target in radiation induced lung injury.Heliyon. 2024 Apr 10;10(8):e29492. doi: 10.1016/j.heliyon.2024.e29492. eCollection 2024 Apr 30. Heliyon. 2024. PMID: 38665580 Free PMC article. Review.
-
Resveratrol relieves HFD-induced insulin resistance in skeletal muscle tissue through antioxidant capacity enhancement and the Nrf2-Keap1 signaling pathway.Mol Biol Rep. 2024 Apr 15;51(1):516. doi: 10.1007/s11033-024-09434-4. Mol Biol Rep. 2024. PMID: 38622329
-
Beneficial Effects of Low-Grade Mitochondrial Stress on Metabolic Diseases and Aging.Yonsei Med J. 2024 Feb;65(2):55-69. doi: 10.3349/ymj.2023.0131. Yonsei Med J. 2024. PMID: 38288646 Free PMC article. Review.
-
A natural Nrf2 activator glucoraphanin improves hepatic steatosis in high-fat diet-induced obese male mice associated with AMPK activation.Diabetol Int. 2023 Aug 29;15(1):86-98. doi: 10.1007/s13340-023-00658-6. eCollection 2024 Jan. Diabetol Int. 2023. PMID: 38264234
-
Zinc homeostasis and redox alterations in obesity.Front Endocrinol (Lausanne). 2024 Jan 8;14:1273177. doi: 10.3389/fendo.2023.1273177. eCollection 2023. Front Endocrinol (Lausanne). 2024. PMID: 38260166 Free PMC article. Review.
References
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical