Hepatic cholesterol transport and its role in non-alcoholic fatty liver disease and atherosclerosis

Li, Heng; Yu, Xiaohua; Ou, Xiang; Ouyang, Xin; Tang, Chao-Ke

doi:10.1016/j.plipres.2021.101109

Cited by 102 publications

(59 citation statements)

References 472 publications

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“…The prevalence of NAFLD in the general population is estimated to be 25% worldwide [ 2 ]. The development of NAFLD is closely related to the abnormal lipid metabolism; variations in intracellular cholesterol transport and imbalance of cholesterol homeostasis in NAFLD can cause the accumulation of hepatic free cholesterol [ 3 ]. The imbalance between lipid intake and disposal leads to the accumulation of hepatic fat [ 4 ]; in addition, NAFLD is often accompanied by a high risk of type 2 diabetes and cardiovascular disease [ 5 ].…”

Section: Introductionmentioning

confidence: 99%

Ficus hirta Vahl. Ameliorates Nonalcoholic Fatty Liver Disease through Regulating Lipid Metabolism and Gut Microbiota

Quan

Zhou

Chen

et al. 2022

Oxidative Medicine and Cellular Longevity

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Nonalcoholic fatty liver disease (NAFLD) has gradually become one of the most serious liver diseases threatening human health in the world. Currently, Chinese herbal medicine is a potentially important treatment option for NAFLD, and the development of effective Chinese herbal medicine has a good prospect. Previous studies have suggested that Ficus hirta Vahl. (FV) has various protective effects on the liver. In this study, we investigated the therapeutic outcomes of FV treatment for the liver disease and its underlying mechanism using HepG2 cell lines induced by palmitate (PA) and mouse model fed with high-fat diet (HFD). FV mainly exerts pharmacological effects by mediating lipid metabolism and inflammation. During the lipid metabolism regulation process, CD36, SREBP-1, SCD1, PPAR γ, ACOX1, and CPT1α are the key factors related to the healing effects of FV on NAFLD. During the inflammation process, the downregulation of IL-6, IL-1β, and TNF-α is involved in alleviation of NAFLD. Furthermore, CD36 overexpression promotes lipid abnormal metabolism and inflammation in PA-induced HepG2 cells, while CD36 knockdown and FV supplementation reverse these responses. In addition, FV also modulates gut microbiota composition, such as Allobaculum, Faecalibaculum, and Butyricicoccus in HFD-fed mice. In summary, our findings demonstrated that FV exerted a beneficial preventive and therapeutic effect on NAFLD by improving lipid metabolism and inflammation as well as regulating the structure of gut microbiota, and therefore, FV may be a candidate for the treatment of NAFLD.

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Section: Introductionmentioning

confidence: 99%

Ficus hirta Vahl. Ameliorates Nonalcoholic Fatty Liver Disease through Regulating Lipid Metabolism and Gut Microbiota

Quan

Zhou

Chen

et al. 2022

Oxidative Medicine and Cellular Longevity

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“…Since cholesterol has many important functions in the physiological environment, disorders of cholesterol metabolism can lead to some congenital and acquired diseases, including familial hypercholesterolemia, Tangier disease, sitosterol disease and arteriosclerotic cardiovascular disease, which are all closely related to AS (Li, Yu et al, 2021). The homeostasis of cholesterol is inseparable from its synthesis, uptake, efflux and esterification (Luo et al, 2020).…”

Section: Discussionmentioning

confidence: 99%

The LEPIS-HuR-TMOD4 axis regulates hepatic cholesterol homeostasis and accelerates atherosclerosis

Pan

et al. 2022

Preprint

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Long noncoding RNAs (lncRNAs) play an important role in the entire progression of atherosclerosis. In this study, we identified an uncharacterized lncRNA, Liver Expressions by PSRC1 Induce Specifically (LEPIS). The expression of LEPIS and its potential target tropomodulin 4 (TMOD4) in the liver of ApoE-/- mice fed a high-fat diet was increased. An ApoE-/- mouse model with the overexpression of LEPIS or TMOD4 in liver was established, and we found that both LEPIS and TMOD4 increased the burden of atherosclerosis and reduced hepatic cholesterol levels. Further study revealed that LEPIS and TMOD4 affect the expression of genes related to hepatic cholesterol homeostasis, including proprotein convertase subtilisin/kexin type9 (PCSK9) and low-density lipoprotein receptor (LDLR), which are closely related to hypercholesterolemia. Mechanistically, human antigen R (HuR), an RNA-binding protein, was found to be recruited from the nucleus to the cytoplasm topromote the expression of TMOD4. These results suggest that the LEPIS-HuR-TMOD4 axis is a potential intervention target for hepatic cholesterol homeostasis and atherosclerosis.

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“…Fourth, do a specific and efficient method to counteract the detrimental actions of IL‑22 on atherogenesis exist in vivo? Finally, reverse cholesterol transport (RCT), an important protective mechanism against the development of atherogenesis, is a dynamic process in which excessive cholesterol from extrahepatic tissues is delivered to the liver for further metabolism and biliary excretion (Rader et al 2009 ; Li et al 2021 ). Therefore, it is of importance to detect whether IL‑22 can increase the efficiency of RCT.…”

Section: Discussionmentioning

confidence: 99%

Interleukin-22: a potential therapeutic target in atherosclerosis

Luo

Liu

et al. 2021

Mol Med

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Background Atherosclerosis is recognized as a chronic immuno-inflammatory disease that is characterized by the accumulation of immune cells and lipids in the vascular wall. In this review, we focus on the latest advance regarding the regulation and signaling pathways of IL-22 and highlight its impacts on atherosclerosis. Main body IL-22, an important member of the IL-10 family of cytokines, is released by cells of the adaptive and innate immune system and plays a key role in the development of inflammatory diseases. The binding of IL-22 to its receptor complex can trigger a diverse array of downstream signaling pathways, in particular the JAK/STAT, to induce the expression of chemokines and proinflammatory cytokines. Recently, numerous studies suggest that IL-22 is involved in the pathogenesis of atherosclerosis by regulation of VSMC proliferation and migration, angiogenesis, inflammatory response, hypertension, and cholesterol metabolism. Conclusion IL-22 promotes the development of atherosclerosis by multiple mechanisms, which may be a promising therapeutic target in the pathogenesis of atherosclerosis.

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Hepatic cholesterol transport and its role in non-alcoholic fatty liver disease and atherosclerosis

Cited by 102 publications

References 472 publications

Ficus hirta Vahl. Ameliorates Nonalcoholic Fatty Liver Disease through Regulating Lipid Metabolism and Gut Microbiota

Ficus hirta Vahl. Ameliorates Nonalcoholic Fatty Liver Disease through Regulating Lipid Metabolism and Gut Microbiota

The LEPIS-HuR-TMOD4 axis regulates hepatic cholesterol homeostasis and accelerates atherosclerosis

Interleukin-22: a potential therapeutic target in atherosclerosis

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