Article
Ovariectomy in mice decreases lipid metabolism-related gene expression in adipose tissue and skeletal muscle with increased body fat.
National Institute of Health and Nutrition, Shinjuku-ku, Tokyo 162-8636, Japan.
Journal of Nutritional Science and Vitaminology (impact factor:
1.2).
05/2005;
51(2):110-7.
pp.110-7
Source: PubMed
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Citations (0)
- Cited In (4)
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Article: Serum cholesterol and expression of ApoAI, LXRbeta and SREBP2 in vitamin D receptor knock-out mice.
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ABSTRACT: Vitamin D insufficiency has been reported to be associated with increased blood cholesterol concentrations. Here we used two strains of VDR knock-out (VDR-KO) mice to study whether a lack of vitamin D action has any effect on cholesterol metabolism. In 129S1 mice, both in male and female VDR-KO mice serum total cholesterol levels were significantly higher than those in wild type (WT) mice (20.7% (P=0.05) and 22.2% (P=0.03), respectively). In addition, the serum high-density lipoprotein-bound cholesterol (HDL-C) level was 22% (P=0.03), respectively higher in male VDR-KO mice than in WT mice. The mRNA expression levels of five cholesterol metabolism related genes in livers of 129S1 mice were studied using quantitative real-time PCR (QRT-PCR): ATP-binding cassette transporter A1 (ABCA1), regulatory element binding protein (SREBP2), apolipoprotein A-I (ApoAI), low-density lipoprotein receptor (LDLR) and liver X receptor beta (LXRbeta). In the mutant male mice, the mRNA level of ApoAI and LXRbeta were 49.2% (P=0.005) and 38.8% (P=0.034) higher than in the WT mice. These changes were not observed in mutant female mice, but the female mutant mice showed 52.5% (P=0.006) decrease of SREBP2 mRNA expression compared to WT mice. Because the mutant mice were fed with a special rescue diet, we wanted to test whether the increased cholesterol levels in mutant mice were due to the diet. Both the WT and mutant NMRI mice were given the same diet for 3 weeks before the blood sampling. No difference in cholesterol or in HDL-C between WT and mutant mice was found. The results suggest that the food, gender and genetic background have an effect on the cholesterol metabolism. Although VDR seems to regulate some of the genes involved in cholesterol metabolism, its role in the regulation of serum cholesterol seems to be minimal.The Journal of steroid biochemistry and molecular biology 03/2009; 113(3-5):222-6. · 2.66 Impact Factor -
Article: Gender-specific effects of HIV protease inhibitors on body mass in mice.
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ABSTRACT: Protease inhibitors, as part of highly active anti-retroviral therapy (HAART), have significantly increased the lifespan of human immunodeficiency virus (HIV) infected patients. Several deleterious side effects including dyslipidemia and lipodystrophy, however, have been observed with HAART. Women are at a higher risk of developing adipose tissue alterations and these alterations have different characteristics as compared to men. We have previously demonstrated that in mice the HIV protease inhibitor, ritonavir, caused a reduction in weight gain in females, but had no effect on male mice. In the present study, we examined the potential causes of this difference in weight gain. Low-density lipoprotein receptor (LDL-R) null mice or wild-type C57BL/6 mice, were administered 15 mug/ml ritonavir or vehicle (0.01% ethanol) in the drinking water for 6 weeks. The percent of total body weight gained during the treatment period was measured and confirmed that female LDL-R gained significantly less weight with ritonavir treatment than males. In wild type mice, however, there was no effect of ritonavir treatment in either sex. Despite the weight loss in LDL-R null mice, ritonavir increased food intake, but no difference was observed in gonadal fat weight. Serum leptin levels were significantly lower in females. Ritonavir further suppressed leptin levels in (p < 0.05). Ritonavir did not alter serum adiponectin levels in either gender. To determine the source of these differences, female mice were ovariectomized remove the gonadal sex hormones. Ovariectomy prevented the weight loss induced by ritonavir (p < 0.05). Furthermore, leptin levels were no longer suppressed by ritonavir (p < 0.05). This study demonstrates that gonadal factors in females influence the hormonal control of weight gain changes induced by HIV protease inhibitors in an environment of elevated cholesterol.AIDS Research and Therapy 02/2007; 4:8. · 2.54 Impact Factor -
Article: Mitochondrial oestrogen receptors and their potential implications in oestrogen carcinogenesis in human breast cancer
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ABSTRACT: Background. Prolonged exposure to oestrogens (17β‐estradiol)(E2), xenoestrogens, hormone replacement therapy and contraceptives has been recognized as a key aetiological factor of human breast cancer. The biological and carcinogenic effects of E2 and xenoestrogens are mediated via oestrogen receptors alpha (ERα) and beta (ERβ). Both receptors are localized in the nucleus of E2‐targeted cells including human breast cells where they are involved in the regulation of nuclear gene expression. There is increasing evidence indicating that a small fraction of total cellular ERs, particularly ERα, are localized in the membrane of E2‐targeted cells where they mediate E2‐dependent and/or E2‐independent rapid and non‐nuclear genomic signal pathways. Results. The present work will present evidence that: (1) there is mitochondrial localization of ERs in human breast cancer cells; (2) there is a functional role of the mitochondrial ERs in the regulation of mitochondrial genes encoding respiratory chain proteins. Conclusions. The potential implications of the mitochondrial ER‐mediated pathways in oestrogen carcinogenesis, particularly in stimulation of cell proliferation and inhibition of apoptosis, in human breast cancer and the potential nutritional and environmental perspectives of these effects will be addressed.07/2009; 17(1):76-89.
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Keywords
acetyl CoA carboxylase
acetyl CoA oxidase
diacyl glycerol acetyl transferase 1
energy expenditure
energy expenditure-related genes
fatty acid beta-oxidation
fatty acid synthase
fatty acid synthesis
gene expression
lipid metabolism
mouse tissues
mRNA levels
nuclear receptors
obese phenotype
Ovariectomy-induced obesity
Postmenopausal women
repressed energy expenditure
skeletal muscle
triglyceride synthesis
weight gain