Vitamin D and the Liver—Correlation or Cause?

Abstract

Vitamin D is becoming increasingly accepted as an important physiological regulator outside of its classical role in skeletal homeostasis. A growing body of evidence connects vitamin D with hepatic disease. This review summarises the role of vitamin D in liver homeostasis and disease and discusses the therapeutic potential of vitamin D-based treatments to protect against hepatic disease progression and to improve response to treatment. While pre-clinical experimental data is promising, clinical trials around liver diseases have mostly been under-powered, and further studies will be required to clarify whether vitamin D or vitamin D analogues have beneficial effects on liver disease.

Vitamin D3 and calcium cosupplementation alleviates cadmium hepatotoxicity in the rat: Enhanced antioxidative and anti‐inflammatory actions by remodeling cellular calcium pathways

“…In contrast, serum VD levels correlated directly with blood and liver Ca 2+ levels, hepatic antioxidant and anti‐inflammatory markers, alongside total protein and albumin. The observed aberrant alterations in hepatic VD molecules could simply be an outcome of Cd‐induced hepatoxicity that consequently resulted in hypovitaminosis D …”

“…In contrast, serum VD levels correlated directly with blood and liver Ca 2+ levels, hepatic antioxidant and anti-inflammatory markers, alongside total protein and albumin. The observed aberrant alterations in hepatic VD molecules could simply be an outcome of Cd-induced hepatoxicity that consequently resulted in hypovitaminosis D. [49] Another construal could be that systemic and hepatic VD dyshomeostases are extra distressing processes adding to the complexity of the pathogenesis of Cd-induced liver injury. In this context, Cdintestinal absorption and toxic effects were more severe with VD 3 [28] and Ca 2+ [29] deficiency, and hepatic tissue Ca 2+ levels were diminished with chronic Cd toxicity.…”

Tomatidine Reduces Palmitate‐Induced Lipid Accumulation by Activating AMPK via Vitamin D Receptor‐Mediated Signaling in Human HepG2 Hepatocytes

“…VDR mRNA and protein are expressed in human hepatocytes, which constitute over 90% of liver mass, whereas rats and mice express little or no VDR mRNA or protein . Recent animal studies have revealed that VDR expression in hepatocytes increases with inflammation, and is induced early in NAFLD . Once bound to VDR, 1,25(OH) 2 D 3 (calcitriol), the active form of vitamin D, acts not only as a genomic transcriptional factor but also as an inducer of rapid non‐genomic intracellular signaling .…”

“…[47] Recent animal studies have revealed that VDR expression in hepatocytes increases with inflammation, and is induced early in NAFLD. [24,25] Once bound to VDR, 1,25(OH) 2 D 3 (calcitriol), the active form of vitamin D, acts not only as a genomic transcriptional factor but also as an inducer of rapid non-genomic intracellular signaling. [48] The non-genomic actions by binding of 1,25(OH) 2 D 3 to the caveolae-associated VDR include activation of the phospholipase C pathway via G q/11 , activation of the adenylate cyclase pathway, Ca 2+ entry through voltage-gated calcium or chloride channels in the plasma membrane, Ca 2+ mobilization from the endoplasmic reticulum, and an increase in cyclic guanosine monophosphate levels.…”

“…Recently, targeting of TGR5, the G-protein-coupled bile acid receptor 1, and VDR, a nuclear hormone receptor, represents an attractive therapeutic approach for NAFLD, given that receptor agonism could improve lipid homeostasis as well as modulate liver injury. [22][23][24][25] A wide range of structurally diverse agonists for both receptors, including steroidal and non-steroidal compounds, have been reported. [26][27][28][29][30][31][32] Based on these facts, we speculated that AMPK-mediated inhibition of lipid accumulation by tomatidine could be attributed to activation of TGR5 and/or VDR.…”