The effects of vitamin D treatment on liver degenerations, apoptosis, and pyroptosis in rats fed with a high-fat and high-fructose diet.


Bayramova ., Zorkaya B., Rzayeva S., Özbilenler ., Akdemir A. S., Gürel Ç., ...Daha Fazla

FOM 2024, Genoa, İtalya, 25 - 27 Mart 2024, sa.9063133, ss.2, (Özet Bildiri)

  • Yayın Türü: Bildiri / Özet Bildiri
  • Basıldığı Şehir: Genoa
  • Basıldığı Ülke: İtalya
  • Sayfa Sayıları: ss.2
  • İstanbul Üniversitesi-Cerrahpaşa Adresli: Evet

Özet

Abstract
Metabolic Syndrome (MetS) is a medical condition characterized by the simultaneous presence of at least three of the
following: obesity, hyperglycemia, hypertension, or dyslipidemia. Its prevalence is increasing worldwide, making it a
significant public health concern (Panchal et al., 2012; Jha et al., 2023). Vitamin D is a regulator of cell proliferation and
differentiation, and has immunomodulatory, anti-inflammatory and anti-fibrotic properties (Kitson & Roberts, 2012). In
this study we aimed to investigate the impact of vitamin D treatment on various aspects of liver degeneration in a
metabolic syndrome (MetS) model induced by a high-fat, high-fructose diet.
In this study, 19 male Sprague Dawley rats were randomly divided into four groups as Control (C), Control group +
vitamin D (C+VD), Metabolic Syndrome (MetS) and Metabolic Syndrome+Vitamin D (MetS+VitD). MetS groups were fed
with high fat (17%)-fructose (17%) chow and 20% fructose water, while the control group was fed with standard chow
and water. Vitamin D supplementation (oral 170 IU/week) was initiated in the treatment groups starting from the third
week of the experiment and continued until the end of the 15th week.
During the study, the weights, fasting blood sugar, waist circumference and calorie intake of all groups were measured.
At the end of the experiment, the liver tissues were fixed and embedded in paraffin blocks. Hematoxylin-Eosin, PAS
and Van Gieson staining were performed on the tissue sections taken for morphological evaluation and detection of
glycogen accumulation and fibrosis. In addition, the immunohistochemistry method was used to analyze the
expression of various proteins (TGF-β1, α-SMA, 8-OHdG, NF-kB, NLRP3, GSDMD, GPX-4, PCNA, VDR) in liver tissue
sections. Apoptotic cell death was measured using the TUNEL method, and serum insulin levels were assessed using
the ELISA method. Statistical analysis was performed on all the obtained results.
Fasting blood sugar and serum insulin levels (p<0.001), weight and waist circumference measurements were found to
increase in the MetS group compared to all other groups, while all these values decreased in the MetS+VD group. In
the MetS group, vacuolization in hepatocytes, dense glycogen accumulations and an increase in binuclear cells were
observed around the vena centralis. In addition, an increased number of NLRP3, GSDMD positive pyroptotic cells were
detected in this region. An increase in α-SMA positive hepatic stellate cells, as well as fibrosis and mild inflammation in
the central vein and portal area were observed. It was determined that VitD treatment improved the histopathology of
hepatocytes, pyroptosis, inflammation and fibrosis, and decreased hepatic expression of α-SMA which is hepatic
stellate cell activation marker. It was shown that TGF-β1, 8-OHdG, NF-kB, GPX-4 protein expressions and apoptotic
index were significantly higher in the MetS group compared to other groups (p<0.001). Especially with vitamin D
treatment, a significant decrease was detected in the expression of these proteins and the apoptotic index (p<0.001).
This study indicates that feeding with a high-fat and high-fructose diet causes liver fibrosis, inflammation, apoptosis
and pyroptosis in the rat liver. Vitamin D application was found to reduce fasting blood sugar levels in MetS, regulate
the liver's response to insulin, and have positive effects on oxidative stress, inflammation, fibrosis, cell death, and
proliferation. The findings highlight the potential role of vitamin D in managing liver degeneration associated with
metabolic syndrome.