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Bardoxolone Methyl Prevents Fat Deposition and Inflammation in Brown Adipose Tissue and Enhances Sympathetic Activity in Mice Fed a High-Fat Diet.

Dinh CH, Szabo A, Yu Y, Camer D, Zhang Q, Wang H, Huang XF - Nutrients (2015)

Bottom Line: We present for the first time the effects of oral BARD treatment on BAT morphology and associated changes in the brainstem.BARD prevented fat deposition in BAT, demonstrated by the decreased accumulation of lipid droplets.Overall, oral BARD prevented fat deposition and inflammation in BAT, and stimulated sympathetic nerve activity.

View Article: PubMed Central - PubMed

Affiliation: Centre for Translational Neuroscience, School of Medicine, University of Wollongong and Illawarra Health and Medical Research Institute, Wollongong, NSW 2522, Australia. hlcd893@uowmail.edu.au.

ABSTRACT
Obesity results in changes in brown adipose tissue (BAT) morphology, leading to fat deposition, inflammation, and alterations in sympathetic nerve activity. Bardoxolone methyl (BARD) has been extensively studied for the treatment of chronic diseases. We present for the first time the effects of oral BARD treatment on BAT morphology and associated changes in the brainstem. Three groups (n = 7) of C57BL/6J mice were fed either a high-fat diet (HFD), a high-fat diet supplemented with BARD (HFD/BARD), or a low-fat diet (LFD) for 21 weeks. BARD was administered daily in drinking water. Interscapular BAT, and ventrolateral medulla (VLM) and dorsal vagal complex (DVC) in the brainstem, were collected for analysis by histology, immunohistochemistry and Western blot. BARD prevented fat deposition in BAT, demonstrated by the decreased accumulation of lipid droplets. When administered BARD, HFD mice had lower numbers of F4/80 and CD11c macrophages in the BAT with an increased proportion of CD206 macrophages, suggesting an anti-inflammatory effect. BARD increased phosphorylation of tyrosine hydroxylase in BAT and VLM. In the VLM, BARD increased energy expenditure proteins, including beta 3-adrenergic receptor (β3-AR) and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α). Overall, oral BARD prevented fat deposition and inflammation in BAT, and stimulated sympathetic nerve activity.

No MeSH data available.


Related in: MedlinePlus

Effect of bardoxolone methyl (BARD) on fat deposition in brown adipose tissue of mice fed: low-fat diet (LFD), high-fat diet (HFD), and high-fat diet supplemented with BARD (HFD/BARD). (A) Haematoxylin and eosin staining of brown fat pads (×40). Bar = 50 µm; (B) Lipid area; (C) Lipid droplet area; (D) Distribution of lipid droplets. All data are presented as mean ± SEM. * p < 0.05, *** p < 0.001.
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nutrients-07-04705-f001: Effect of bardoxolone methyl (BARD) on fat deposition in brown adipose tissue of mice fed: low-fat diet (LFD), high-fat diet (HFD), and high-fat diet supplemented with BARD (HFD/BARD). (A) Haematoxylin and eosin staining of brown fat pads (×40). Bar = 50 µm; (B) Lipid area; (C) Lipid droplet area; (D) Distribution of lipid droplets. All data are presented as mean ± SEM. * p < 0.05, *** p < 0.001.

Mentions: In histological micrographs, HFD mice had larger lipid droplets than LFD and HFD/BARD mice (Figure 1A). HFD mice had an 82% increase in lipid area compared with the LFD mice (p < 0.001) (Figure 1B). Supplementing the diet with BARD reduced the lipid area by 38% compared to HFD mice (p < 0.001). Compared to the LFD mice, HFD mice had a five-fold increase in lipid droplet diameter (p < 0.001) (Figure 1C). In contrast the diameter of lipid droplets decreased three-fold when HFD mice were administered BARD (p < 0.001). Additionally, HFD/BARD mice had larger numbers of small lipid droplets compared with HFD mice (Figure 1D). This data indicated a preventive effect of BARD on HFD-induced fat deposition in BAT.


Bardoxolone Methyl Prevents Fat Deposition and Inflammation in Brown Adipose Tissue and Enhances Sympathetic Activity in Mice Fed a High-Fat Diet.

Dinh CH, Szabo A, Yu Y, Camer D, Zhang Q, Wang H, Huang XF - Nutrients (2015)

Effect of bardoxolone methyl (BARD) on fat deposition in brown adipose tissue of mice fed: low-fat diet (LFD), high-fat diet (HFD), and high-fat diet supplemented with BARD (HFD/BARD). (A) Haematoxylin and eosin staining of brown fat pads (×40). Bar = 50 µm; (B) Lipid area; (C) Lipid droplet area; (D) Distribution of lipid droplets. All data are presented as mean ± SEM. * p < 0.05, *** p < 0.001.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4488809&req=5

nutrients-07-04705-f001: Effect of bardoxolone methyl (BARD) on fat deposition in brown adipose tissue of mice fed: low-fat diet (LFD), high-fat diet (HFD), and high-fat diet supplemented with BARD (HFD/BARD). (A) Haematoxylin and eosin staining of brown fat pads (×40). Bar = 50 µm; (B) Lipid area; (C) Lipid droplet area; (D) Distribution of lipid droplets. All data are presented as mean ± SEM. * p < 0.05, *** p < 0.001.
Mentions: In histological micrographs, HFD mice had larger lipid droplets than LFD and HFD/BARD mice (Figure 1A). HFD mice had an 82% increase in lipid area compared with the LFD mice (p < 0.001) (Figure 1B). Supplementing the diet with BARD reduced the lipid area by 38% compared to HFD mice (p < 0.001). Compared to the LFD mice, HFD mice had a five-fold increase in lipid droplet diameter (p < 0.001) (Figure 1C). In contrast the diameter of lipid droplets decreased three-fold when HFD mice were administered BARD (p < 0.001). Additionally, HFD/BARD mice had larger numbers of small lipid droplets compared with HFD mice (Figure 1D). This data indicated a preventive effect of BARD on HFD-induced fat deposition in BAT.

Bottom Line: We present for the first time the effects of oral BARD treatment on BAT morphology and associated changes in the brainstem.BARD prevented fat deposition in BAT, demonstrated by the decreased accumulation of lipid droplets.Overall, oral BARD prevented fat deposition and inflammation in BAT, and stimulated sympathetic nerve activity.

View Article: PubMed Central - PubMed

Affiliation: Centre for Translational Neuroscience, School of Medicine, University of Wollongong and Illawarra Health and Medical Research Institute, Wollongong, NSW 2522, Australia. hlcd893@uowmail.edu.au.

ABSTRACT
Obesity results in changes in brown adipose tissue (BAT) morphology, leading to fat deposition, inflammation, and alterations in sympathetic nerve activity. Bardoxolone methyl (BARD) has been extensively studied for the treatment of chronic diseases. We present for the first time the effects of oral BARD treatment on BAT morphology and associated changes in the brainstem. Three groups (n = 7) of C57BL/6J mice were fed either a high-fat diet (HFD), a high-fat diet supplemented with BARD (HFD/BARD), or a low-fat diet (LFD) for 21 weeks. BARD was administered daily in drinking water. Interscapular BAT, and ventrolateral medulla (VLM) and dorsal vagal complex (DVC) in the brainstem, were collected for analysis by histology, immunohistochemistry and Western blot. BARD prevented fat deposition in BAT, demonstrated by the decreased accumulation of lipid droplets. When administered BARD, HFD mice had lower numbers of F4/80 and CD11c macrophages in the BAT with an increased proportion of CD206 macrophages, suggesting an anti-inflammatory effect. BARD increased phosphorylation of tyrosine hydroxylase in BAT and VLM. In the VLM, BARD increased energy expenditure proteins, including beta 3-adrenergic receptor (β3-AR) and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α). Overall, oral BARD prevented fat deposition and inflammation in BAT, and stimulated sympathetic nerve activity.

No MeSH data available.


Related in: MedlinePlus