Therapeutic effects of vitamin D and intermittent fasting on metabolic associated steatotic liver disease in rats

Abstract

Metabolic associated steatotic liver disease (MASLD) is a globally prevalent metabolic disorder characterized by hepatic steatosis, inflammation, and impaired lipid homeostasis. Vitamin D exhibits anti-inflammatory and insulin-sensitizing properties, whereas intermittent fasting (IF) has recently emerged as a metabolic intervention capable of improving hepatic and systemic energy balance. To compare the therapeutic effects of vitamin D and IF on high-fat and fructose diet-induced MASLD in rats, with emphasis on lipid metabolism, oxidative stress, and inflammatory signaling pathways. Twenty-four male Sprague-Dawley rats were allocated into four groups (n = 6/group): Control, MASLD (HFD), HFD + vitamin D, and HFD + IF. Biochemical analyses included fasting glucose, serum insulin, ALT, AST, lipid profile, MDA, and GSH. Immunohistochemistry quantified hepatic expression of SREBP1, AQP9, TLR4, and NF-κB. Numerical comparisons were reported as mean ± SD and percentage changes relative to HFD. Both interventions significantly improved MASLD outcomes. Vitamin D and IF reduced ALT by 42% and 47%, respectively, and lowered AST by 38% and 45% compared with HFD. Triglycerides and LDL-C decreased by 31-48%, while HDL-C increased by 18-24%. Oxidative stress improved, with MDA reduced by 36% (vitamin D) and 54% (IF), and GSH elevated by 61% and 82%, respectively. Both treatments markedly downregulated hepatic SREBP1 and the AQP9 glycerol transport pathway, and suppressed activation of TLR4/NF-κB signaling. Vitamin D and intermittent fasting exert significant hepatoprotective effects in MASLD by improving metabolic parameters, enhancing antioxidant capacity, and attenuating inflammatory signaling. These findings support their potential as complementary, non-pharmacological strategies for MASLD management and warrant further translational investigation.