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

Abstract

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 1α, 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-α, 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 60-70% 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. © 2012 The Authors. Basic & Clinical Pharmacology & Toxicology © 2012 Nordic Pharmacological Society.