Hepatology Communications · 8 authors, 1 centre
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This narrative review summarizes the roles of nuclear receptors in regulating cholesterol production, excretion, and storage in the liver, as well as their cross talk in reverse cholesterol transport within the context of NAFLD pathogenesis and progression. The central conclusion is that dysregulation of nuclear receptors disrupts cholesterol homeostasis, which is a key driver of NAFLD.
This narrative review synthesizes literature on the role of nuclear receptors (NRs) in cholesterol metabolism and reverse cholesterol transport (RCT) in nonalcoholic fatty liver disease (NAFLD). It describes how NRs like LXR, FXR, PPAR, PXR, HNF4α, and Nur77 regulate the three main aspects of cholesterol homeostasis: production, excretion, and storage. The central conclusion is that NR dysregulation disrupts energy metabolism via the gut-liver-adipose axis, with cholesterol imbalance being crucial to NAFLD onset. Limitations include that the review is a synthesis of existing literature and does not provide primary data, and the specific roles of some NRs, like FXR in human NASH, require further investigation. Implications point toward novel therapeutic strategies targeting NRs.
