Recent developments in the regulation of cholesterol transport by natural molecules

Abstract

The dysregulation of cholesterol metabolism is a high-risk factor for non-alcoholic fatty liver disease (NAFLD), dyslipidemia, and atherosclerosis (AS). Cholesterol transport maintains whole-body cholesterol homeostasis. Low-density apolipoprotein receptor (LDLR) mediates cholesterol uptake in cells and plays an important role in the primary route of circulatory cholesterol clearance in liver cells. Caveolins 1 is an integral membrane protein and shuttle between the cytoplasm and cell membrane. Caveolins 1 not only plays a role in promoting cholesterol absorption in cells but also in the transport of cellular cholesterol efflux by interacting with the ATP-binding cassette transporter A1 (ABCA1) and scavenger receptor class B type I (SR-BI). These proteins, which are associated with reverse cholesterol transport (RCT), are potential therapeutic targets for NAFLD and AS. Many studies have indicated that natural products have lipidlowering effects. Moreover, natural molecules, derived from natural products, have the potential to be developed into novel drugs. However, the mechanisms underlying the regulation of cholesterol transport by natural molecules have not yet been adequately investigated. In this review, we briefly describe the process of cholesterol transport and summarize the mechanisms by which molecules regulate cholesterol transport.This article provides an overview of recent studies and focuses on the potential therapeutic effects of natural molecules; however, further high-quality studies are needed to firmly establish the clinical efficacies of natural molecules.

The interaction between polyphyllin I and SQLE protein induces hepatotoxicity through SREBP-2/HMGCR/SQLE/LSS pathway

“…Notably, the cholesterol biosynthetic process and metabolism pathways stood out in the proteomics and transcriptome data sets. As we know, cholesterol, a basic substance for life-sustaining activities [ 25 ], is not only important for the maintenance of blood circulation, including T-CHO and high-/low-density lipoprotein-cholesterol [ [26] , [27] , [28] ], but also the precursor of bile acid biosynthesis [ 29 ], which plays a key role in preventing the accumulation of toxic metabolites as well as violations of the liver and other organs [ 30 ]. The liver is the main organ of cholesterol synthesis which is represented by an intricate and multistep pathway [ 31 ].…”

Hepatic steatosis is associated with dysregulated cholesterol metabolism and altered protein acetylation dynamics in chickens

“…Cholesterol homeostasis is an important factor for liver health, and elevated liver cholesterol can induce hepatic steatosis [ 61 , 68 ]. Cholesterol is one of the basic components of cell membranes and is an essential precursor for the synthesis of bile acids and steroid hormones [ 69 ].…”

“…Another important aspect of maintaining cholesterol dynamic balance is the transport of intracellular cholesterol. Excess cholesterol from the blood and endogenous cholesterol from food bind to lipoproteins and are transported into the liver as HDLs and CMs [ 47 , 68 ]. The levels of apolipoproteins (APOA and APOC) involved in these processes were significantly elevated in the hepatic steatosis group in this study, indicating an increase in exogenous cholesterol transport.…”

Target Deconvolution of Fenofibrate in Nonalcoholic Fatty Liver Disease Using Bioinformatics Analysis

“…SCARB1 (scavenger receptor class B, type I) is a high-density lipoprotein (HDL) receptor that facilitates uptake of cholesterol (Cho) from HDL to hepatocytes [ 112 , 113 ]. Recently, it has been suggested that SCARB1 may be associated with NAFLD [ 114 ] and several studies suggest that fenofibrate affects SCARB1 [ 115 – 117 ]. Those studies have proposed that fenofibrate may enhance the degradation of SCARB1 in a postendoplasmic reticulum or postplasma membrane compartment [ 115 ].…”