Vitamin D/vitamin D receptor pathway in non-alcoholic fatty liver disease

ABSTRACT

Introduction

Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease worldwide, but underlying mechanisms are not fully understood. In recent years, a growing body of evidence has emphasized the therapeutic role of vitamin D in NAFLD, but the specific mechanism remains to be investigated.

Areas covered

This review summarized the roles of vitamin D/VDR (vitamin D receptor) pathway in different types of liver cells (such as hepatocytes, hepatic stellate cells, liver macrophages, T lymphocytes, and other hepatic immune cells) in case of NAFLD. Meanwhile, the effects of pathways in the gut-liver axis, adipose tissue-liver axis, and skeletal muscle-liver axis on the development of NAFLD were further reviewed. Relevant literature was searched on PubMed for the writing of this review.

Expert opinion

The precise regulation of regional vitamin D/VDR signaling pathway based on cell-specific or tissue-specific function will help clarify the potential mechanism of vitamin D in NAFLD, which may provide new therapeutic targets to improve the safety and efficacy of vitamin D based drugs.

GRAPHICAL ABSTRACT

KEYWORDS:

• Adipose tissue
• gut-liver axis
• hepatic cells
• non-alcoholic fatty liver disease
• skeletal muscle
• vitamin D

Article highlights

• Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease worldwide, but there is no specific pharmacological intervention for NAFLD.

• Vitamin D deficiency is prevalent in NAFLD patients. However, the relationship between vitamin D and NAFLD is still unclear.

• Vitamin D receptor (VDR) is mainly expressed in non-parenchymal cells rather than hepatocytes in the normal liver.

• Vitamin D/VDR pathway can affect hepatic lipogenesis and bile acid circulation in the hepatocytes, improve hepatic inflammation by controlling the hepatic macrophages polarization, maintain immune homeostasis by regulating T lymphocytes and other immune cells in the liver, and inhibit liver fibrosis by inhibiting hepatic stellate cells activation.

• In addition, vitamin D/VDR pathway can also alleviate NAFLD by improving intestinal permeability, intestinal microbial metabolites, adipose inflammation, muscle dysfunction and others through the interplay between liver and extrahepatic tissues (such as gut, adipose tissues, and muscles).

• Selective hepatic cell populations or extra-hepatic tissues are targets for the vitamin D/VDR pathway in the future, which may contribute to NAFLD treatment.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Additional information

Funding

The manuscript was funded by the Foundation of Fujian Key Laboratory of Vascular Aging (grant number XHZDSYS202204) and Fujian Provincial Natural Science Foundation projects (grant number 2019J01558 and 2020J01122587).