Calcitriol Attenuates Weight-Related Systemic Inflammation and Ultrastructural Changes in the Liver in a Rodent Model

被引:21
作者
Alkharfy, Khalid M. [1 ,2 ,3 ]
Al-Daghri, Nasser M. [2 ,3 ,4 ]
Yakout, Sobhy M. [3 ,4 ]
Ahmed, Mukhtar [5 ]
机构
[1] King Saud Univ, Dept Clin Pharm, Coll Pharm, Riyadh 11451, Saudi Arabia
[2] King Saud Univ, Biomarkers Res Program, Riyadh 11451, Saudi Arabia
[3] King Saud Univ, Prince Mutaib Chair Biomarkers Osteoporosis, Riyadh 11451, Saudi Arabia
[4] King Saud Univ, Coll Sci, Dept Biochem, Riyadh 11451, Saudi Arabia
[5] King Saud Univ, Coll Sci Res Ctr, Transmiss Electron Microscope Unit, Riyadh 11451, Saudi Arabia
关键词
HIGH-FAT DIET; INSULIN-RECEPTOR GENE; INDUCED DIABETIC-RATS; VITAMIN-D-RECEPTOR; 1,25-DIHYDROXYVITAMIN D-3; CARDIOVASCULAR-DISEASE; OXIDATIVE STRESS; C57BL/6J MICE; EXPRESSION; RESISTANCE;
D O I
10.1111/j.1742-7843.2012.00936.x
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
The role of vitamin D in maintaining calcium homoeostasis and bone mineralization is well-established. The aim of the current investigation was to evaluate the effect of calcitriol treatment on inflammation, insulin resistance and liver changes induced by increased body-weight. Four groups of mice (n = 11 each) were maintained on either low-fat diet (LFD) or high-fat diet (HFD) with and without 1a, 25-dihydroxyvitamin D3 (calcitriol) for 16 weeks. Body-weight of animals was recorded at the start of the study and every 4 weeks thereafter. At the end of the experiment, blood samples were collected for the determination of biochemical parameters, and liver tissues were harvested for the histopathological evaluation. A significant gradual decrease in weight was observed in HFD-fed mice treated with calcitriol compared with a steady increase in controls (p < 0.01). Furthermore, calcitriol treatment reduced concentrations of various inflammatory markers including TNF-a, CRP and IL-6 (p < 0.05). Treated animals also exhibited lower levels of C-peptide and insulin (539.4 ng/ml versus 718.9 ng/ml and 0.77 ng/ml versus 1.7 ng/ml, respectively; p < 0.05), which are consistent with improved insulin resistance. Liver histology and ultrastructural studies showed a marked accumulation of fat droplets in approximately 6070% of hepatocytes of mice fed on HFD, while calcitriol administration rendered the whole structure more normal. Overall, our data signify an important effect of calcitriol on inflammation under HFD conditions and a protective effect on the liver structure.
引用
收藏
页码:42 / 49
页数:8
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