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Chem Biol Interact. 2016 Jan 5;243:10-8. doi: 10.1016/j.cbi.2015.11.018. Epub 2015 Nov 27.

Bardoxolone methyl prevents the development and progression of cardiac and renal pathophysiologies in mice fed a high-fat diet.

Author information

1
Centre for Translational Neuroscience, School of Medicine, University of Wollongong and Illawarra Health and Illawarra Health and Medical Research Institute, Wollongong, NSW, 2522, Australia.
2
Centre for Translational Neuroscience, School of Medicine, University of Wollongong and Illawarra Health and Illawarra Health and Medical Research Institute, Wollongong, NSW, 2522, Australia; ANSTO LifeSciences, Australian Nuclear Science and Technology Organisation, NSW, 2234, Australia.
3
Centre for Translational Neuroscience, School of Medicine, University of Wollongong and Illawarra Health and Illawarra Health and Medical Research Institute, Wollongong, NSW, 2522, Australia. Electronic address: xhuang@uow.edu.au.

Abstract

Obesity caused by the consumption of a high-fat (HF) diet is a major risk factor for the development of associated complications, such as heart and kidney failure. A semi-synthetic triterpenoid, bardoxolone methyl (BM) was administrated to mice fed a HF diet for 21 weeks to determine if it would prevent the development of obesity-associated cardiac and renal pathophysiologies. Twelve week old male C57BL/6J mice were fed a lab chow (LC), HF (40% fat), or a HF diet supplemented with 10 mg/kg/day BM in drinking water. After 21 weeks, the left ventricles of hearts and cortex of kidneys of mice were collected for analysis. Histological analysis revealed that BM prevented HF diet-induced development of structural changes in the heart and kidneys. BM prevented HF diet-induced decreases in myocyte number in cardiac tissue, although this treatment also elevated cardiac endothelin signalling molecules. In the kidneys, BM administration prevented HF diet-induced renal corpuscle hypertrophy and attenuated endothelin signalling. Furthermore, in both the hearts and kidneys of mice fed a HF diet, BM administration prevented HF diet-induced increases in fat accumulation, macrophage infiltration and tumour necrosis factor alpha (TNFα) gene expression. These findings suggest that BM prevents HF diet-induced developments of cardiac and renal pathophysiologies in mice fed a chronic HF diet by preventing inflammation. Moreover, these results suggest that BM has the potential as a therapeutic for preventing obesity-induced cardiac and renal pathophysiologies.

KEYWORDS:

Bardoxolone methyl; Heart; High-fat diets; Kidney; Obesity

PMID:
26612656
DOI:
10.1016/j.cbi.2015.11.018
[Indexed for MEDLINE]

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