Vitamins and non-alcoholic fatty liver disease: A Molecular Insight⋆ - PubMed (original) (raw)

Vitamins and non-alcoholic fatty liver disease: A Molecular Insight⋆

Sana Raza et al. Liver Res. 2021 Jun.

Abstract

The incidence of non-alcoholic fatty liver disease (NAFLD) is rising rapidly across the globe. NAFLD pathogenesis is largely driven by an imbalance in hepatic energy metabolism and at present, there is no approved drug for its treatment. The liver plays a crucial role in micronutrient metabolism and deregulation of this micronutrient metabolism may contribute to the pathogenesis of NAFLD. Vitamins regulate several enzymatic processes in the liver, and derangement in vitamin metabolism is believed to play a critical role in NAFLD progression. The anti-oxidant activities of vitamin C and E have been attributed to mitigate hepatocyte injury, and alterations in the serum levels of vitamin D, vitamin B12 and folate have shown a strong correlation with NAFLD severity. This review aims to highlight the role of these vitamins, which represent promising therapeutic targets for the management of NAFLD.

Keywords: Antioxidant; Autophagy; Non-alcoholic fatty liver disease (NAFLD); Non-alcoholic steatohepatitis (NASH); Vitamin A; Vitamin B; Vitamin C; Vitamin D; Vitamin E.

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Conflict of interest statement

Declaration of competing interest The authors declare that they have no conflict of interest. Declarations of interest: none

Figures

Fig. 1

Fig. 1

The roles of vitamin E in regulating hepatic oxidative stress, inflammation and apoptosis. Vitamin E lowers inflammatory response by increasing the expression of adiponectin and suppresses the expression of several cytokines including tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1, IL-2, IL-4, IL-6, and IL-8. It also acts as a scavenger of hydroxyl, peroxyl and superoxide radicals and stimulates superoxide dismutase (SOD) levels. Vitamin E exerts anti-apoptotic effects by enhancing the levels of anti-apoptotic protein BCL-2, and lowers the pro-apoptotic proteins BCL-2 associated-X (BAX) protein and p53. Abbreviations: NADPH, nicotinamide adenine dinucleotide phosphate; TGF, transforming growth factor.

Fig. 2

Fig. 2

Vitamin D stimulates insulin secretion in pancreatic β-cells. Vitamin D is involved in direct stimulation of insulin secretion through binding to the vitamin D receptor (VDR) expressed by the pancreatic β-cells and activates the transcription of human insulin. An additional effect of vitamin D is the regulation of calcium flux through pancreatic β-cells. Insulin secretion is a calcium dependent process, therefore, vitamin D affects insulin secretion by modulating changes in calcium concentration. Abbreviations: ADP, adenosine diphosphate; ATP, adenosine triphosphate; GLUT, glucose transporter; RXR, retinoid-X-receptor.

Fig. 3

Fig. 3

Modulation of hepatic pathophysiology by vitamin D. Vitamin D acts as a modulator of insulin sensitivity and is involved in the transcriptional regulation of immune cell proliferation and differentiation. Vitamin D attenuates hepatic steatosis by inducing autophagy and exerts anti-inflammatory and anti-fibrotic effects through vitamin D signaling. Abbreviations: FFA, free fatty acid; HSCs, hepatic stellate cells; RXR, retinoid-X-receptor; TGF-β, transforming growth factor-beta; TNF-α, tumor necrosis factor-alpha; VDR, vitamin D receptor.

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