Recent insights into the pathogenesis and therapeutic targets of chronic liver diseases

Wen, Yankai; Ma, Lichun; Ju, Cynthia

doi:10.1136/egastro-2023-100020

Cited by 3 publications

(1 citation statement)

References 135 publications

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“…NAFLD is a chronic liver disease characterized by diffuse liver cell steatosis [30], [31]. NAFLD date from NAFL, NASH, gradually worsens to related cirrhosis and finally develops into HCC [32], [33]. Further research shows that lipid accumulation, inflammation and other factors can aggravate and amplify the lipid metabolism and inflammation of the liver [34].…”

Section: Discussionmentioning

confidence: 99%

NUP85 alleviates lipid metabolism and inflammation by regulating PI3K/AKT signaling pathway in nonalcoholic fatty liver disease

Wu,

Yan,

Yue

et al. 2024

Int. J. Biol. Sci.

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Nonalcoholic fatty liver disease (NAFLD) is one of the common causes of chronic liver disease in the world. The problem of NAFLD had become increasingly prominent. However, its pathogenesis is still indistinct. As we all know, NAFLD begins with the accumulation of triglyceride (TG), leading to fatty degeneration, inflammation and other liver tissues damage. Notably, structure of nucleoporin 85 (NUP85) is related to lipid metabolism and inflammation of liver diseases. In this study, the results of researches indicated that NUP85 played a critical role in NAFLD. Firstly, the expression level of NUP85 in methionine-choline-deficient (MCD)-induced mice increased distinctly, as well as the levels of fat disorder and inflammation. On the contrary, knockdown of NUP85 had the opposite effects. In vitro , AML-12 cells were stimulated with 2 mm free fatty acids (FFA) for 24 h. Results also proved that NUP85 significantly increased in model group, and increased lipid accumulation and inflammation level. Besides, NUP85 protein could interact with C-C motif chemokine receptor 2 (CCR2). Furthermore, when NUP85 protein expressed at an extremely low level, the expression level of CCR2 protein also decreased, accompanied with an inhibition of phosphorylation of phosphoinositol-3 kinase (PI3K)-protein kinase B (AKT) signaling pathway. What is more, trans isomer (ISRIB), a targeted inhibitor of NUP85, could alleviate NAFLD. In summary, our findings suggested that NUP85 functions as an important regulator in NAFLD through modulation of CCR2.

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Section: Discussionmentioning

confidence: 99%

NUP85 alleviates lipid metabolism and inflammation by regulating PI3K/AKT signaling pathway in nonalcoholic fatty liver disease

Wu,

Yan,

Yue

et al. 2024

Int. J. Biol. Sci.

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The role of interleukin-20 in liver disease: Functions, mechanisms and clinical applications

Wang,

Zhan,

et al. 2024

Heliyon

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Novel insights into causal effects of serum lipids and lipid-modifying targets on cholelithiasis

Chen,

Qiu,

Sun

et al. 2023

Gut

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ObjectiveDifferent serum lipids and lipid-modifying targets should affect the risk of cholelithiasis differently, however, whether such effects are causal is still controversial and we aimed to answer this question.DesignWe prospectively estimated the associations of four serum lipids with cholelithiasis in UK Biobank using the Cox proportional hazard model, including total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and triglycerides (TG). Furthermore, we estimated the causal associations of the genetically predicted serum lipids with cholelithiasis in Europeans using the Mendelian randomisation (MR) design. Finally, both drug-target MR and colocalisation analyses were performed to estimate the lipid-modifying targets’ effects on cholelithiasis, includingHMGCR,NPC1L1,PCSK9,APOB, LDLR, ACLY, ANGPTL3, MTTP, PPARA, PPARDandPPARG.ResultsWe found that serum levels of LDL-C and HDL-C were inversely associated with cholelithiasis risk and such associations were linear. However, the serum level of TC was non-linearly associated with cholelithiasis risk where lower TC was associated with higher risk of cholelithiasis, and the serum TG should be in an inverted ‘U-shaped’ relationship with it. The MR analyses supported that lower TC and higher TG levels were two independent causal risk factors. The drug-target MR analysis suggested thatHMGCRinhibition should reduce the risk of cholelithiasis, which was corroborated by colocalisation analysis.ConclusionLower serum TC can causally increase the risk of cholelithiasis. The cholelithiasis risk would increase with the elevation of serum TG but would decrease when exceeding 2.57 mmol/L. The use ofHMGCRinhibitors should prevent its risk.

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Recent insights into the pathogenesis and therapeutic targets of chronic liver diseases

Cited by 3 publications

References 135 publications

NUP85 alleviates lipid metabolism and inflammation by regulating PI3K/AKT signaling pathway in nonalcoholic fatty liver disease

NUP85 alleviates lipid metabolism and inflammation by regulating PI3K/AKT signaling pathway in nonalcoholic fatty liver disease

The role of interleukin-20 in liver disease: Functions, mechanisms and clinical applications

Novel insights into causal effects of serum lipids and lipid-modifying targets on cholelithiasis

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