Interleukin-1 Receptor Signaling Mediates Atherosclerosis Associated With Bacterial Exposure and/or a High-Fat Diet in a Murine Apolipoprotein E Heterozygote Model

Xanthorrhizol, a natural compound isolated fromCurcuma xanthorrhizaRoxb. (Java turmeric), has been reported to possess antioxidant and anticancer properties; however, its effects on metabolic disorders remain unknown. The aim of the present study was to evaluate the effects of xanthorrhizol (XAN) andC. xanthorrhizaextract (CXE) with standardized XAN on hyperglycemia and inflammatory markers in high-fat diet- (HFD-) induced obese mice. Treatment with XAN (10 or 25 mg/kg/day) or CXE (50 or 100 mg/kg/day) significantly decreased fasting and postprandial blood glucose levels in HFD-induced obese mice. XAN and CXE treatments also lowered insulin, glucose, free fatty acid (FFA), and triglyceride (TG) levels in serum. Epididymal fat pad and adipocyte size were decreased by high doses of XAN (26.6% and 20.1%) and CXE (25.8% and 22.5%), respectively. XAN and CXE treatment also suppressed the development of fatty liver by decreasing liver fat accumulation. Moreover, XAN and CXE significantly inhibited production of inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), interleukin-1β(IL-1β), and C-reactive protein (CRP) in adipose tissue (27.8–82.7%), liver (43.9–84.7%), and muscle (65.2–92.5%). Overall, these results suggest that XAN and CXE, with their antihyperglycemic and anti-inflammatory activities, might be used as potent antidiabetic agents for the treatment of type 2 diabetes.

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Effects of atorvastatin and/or probucol on recovery of atherosclerosis in high-fat-diet-fed apolipoprotein E–deficient mice

Biomedicine & Pharmacotherapy ◽

10.1016/j.biopha.2018.10.184 ◽

2019 ◽

Vol 109 ◽

pp. 1445-1453 ◽

Cited By ~ 4

Author(s):

Xiaokun Guo ◽

Lin Wang ◽

Xiaoshuang Xia ◽

Peilu Wang ◽

Xin Li

Keyword(s):

Apolipoprotein E ◽

High Fat Diet ◽

High Fat ◽

Deficient Mice

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Androgen Receptor-Dependent and Independent Atheroprotection by Testosterone in Male Mice

Endocrinology ◽

10.1210/en.2010-0663 ◽

2010 ◽

Vol 151 (11) ◽

pp. 5428-5437 ◽

Cited By ~ 58

Author(s):

Johan Bourghardt ◽

Anna S. K. Wilhelmson ◽

Camilla Alexanderson ◽

Karel De Gendt ◽

Guido Verhoeven ◽

...

Keyword(s):

Androgen Receptor ◽

Apolipoprotein E ◽

High Fat Diet ◽

Atherosclerotic Lesion ◽

Male Mice ◽

Wild Type ◽

High Fat ◽

Lesion Area ◽

Major Pathway

The atheroprotective effect of testosterone is thought to require aromatization of testosterone to estradiol, but no study has adequately addressed the role of the androgen receptor (AR), the major pathway for the physiological effects of testosterone. We used AR knockout (ARKO) mice on apolipoprotein E-deficient background to study the role of the AR in testosterone atheroprotection in male mice. Because ARKO mice are testosterone deficient, we sham operated or orchiectomized (Orx) the mice before puberty, and Orx mice were supplemented with placebo or a physiological testosterone dose. From 8 to 16 wk of age, the mice consumed a high-fat diet. In the aortic root, ARKO mice showed increased atherosclerotic lesion area (+80%, P < 0.05). Compared with placebo, testosterone reduced lesion area both in Orx wild-type (WT) mice (by 50%, P < 0.001) and ARKO mice (by 24%, P < 0.05). However, lesion area was larger in testosterone-supplemented ARKO compared with testosterone-supplemented WT mice (+57%, P < 0.05). In WT mice, testosterone reduced the presence of a necrotic core in the plaque (80% among placebo-treated vs. 12% among testosterone-treated mice; P < 0.05), whereas there was no significant effect in ARKO mice (P = 0.20). In conclusion, ARKO mice on apolipoprotein E-deficient background display accelerated atherosclerosis. Testosterone treatment reduced atherosclerosis in both WT and ARKO mice. However, the effect on lesion area and complexity was more pronounced in WT than in ARKO mice, and lesion area was larger in ARKO mice even after testosterone supplementation. These results are consistent with an AR-dependent as well as an AR-independent component of testosterone atheroprotection in male mice.

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