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 16weeks. Body-weight of animals was recorded at the start of the study and every 4weeks 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 (539.4ng/ml versus 718.9ng/ml and 0.77ng/ml versus 1.7ng/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.