LIX1L aggravates MASH-HCC progression by reprogramming of hepatic metabolism and microenvironment via CD36 DOI Creative Commons

Yingrong Leng,

Yanqiu Zhang, Cheng Yang

et al.

Pharmacological Research, Journal Year: 2024, Volume and Issue: unknown, P. 107567 - 107567

Published: Dec. 1, 2024

Limb expression 1-like protein (LIX1L) is an essential player in liver disorders, but its function metabolic dysfunction-associated steatohepatitis (MASH) and associated hepatocellular carcinoma (HCC) progression remains obscure. Here, we identify LIX1L as a key integrative regulator linking lipid metabolism inflammation, adipose tissue hepatic microenvironment, which promotes MASH progression. significantly upregulates patients, mouse models, palmitic acid-stimulated hepatocytes. Lix1l deletion inhibits accumulation, fibrosis well adipocyte differentiation by downregulating CD36, alleviating HCC mice. Mechanistically, stress PARP1-mediated poly-ADP-ribosylation of to increase stability RNA binding ability LIX1L. Subsequently, binds AU-rich element the 3'UTR CDS CD36 mRNA, thus mitigating mRNA decay. Furthermore, deficiency-mediated downregulation reprograms tumor-prone microenvironment with increased cytotoxic T lymphocytes reduced immunosuppressive cell proportions. These data indicate systematic pathogenesis underscore targeting PARP1/LIX1L/CD36 axis feasible strategy for treatment HCC.

Language: Английский

Drug Advances in NAFLD: Individual and Combination Treatment Strategies of Natural Products and Small-Synthetic-Molecule Drugs DOI Creative Commons

Xing Wan,

Jingyuan Ma,

He Bai

et al.

Biomolecules, Journal Year: 2025, Volume and Issue: 15(1), P. 140 - 140

Published: Jan. 17, 2025

Non-alcoholic fatty liver disease (NAFLD) has become the most common chronic and is closely associated with metabolic diseases such as obesity, type 2 diabetes mellitus (T2DM), syndrome. However, effective treatment strategies for NAFLD are still lacking. In recent years, progress been made in understanding pathogenesis of NAFLD, identifying multiple therapeutic targets providing new directions drug development. This review summarizes advances focusing on mechanisms action natural products, small-synthetic-molecule drugs, combination therapy strategies. aims to provide insights treating NAFLD.

Language: Английский

Citations

2
SLC13A2 promotes hepatocyte metabolic remodeling and liver regeneration by enhancing de novo cholesterol biosynthesis DOI Creative Commons

Li Shi,

Chen Hao, Y. Zhang

et al.

The EMBO Journal, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 17, 2025

Metabolic requirements of dividing hepatocytes are prerequisite for liver regeneration after injury. In contrast to transcriptional dynamics during repair, its metabolic dependencies remain poorly defined. Here, we screened genes differentially regulated regeneration, and report that SLC13A2, a transporter TCA cycle intermediates, is decreased in rapid response partial hepatectomy mice recovered along restoration mass function. Liver-specific overexpression or depletion SLC13A2 promoted attenuated respectively. increased cleavage SREBP2, expression cholesterol metabolism genes, including LDLR HMGCR. Mechanistically, promotes import citrate into hepatocytes, serving as building block ACLY-dependent acetyl-CoA formation de novo synthesis cholesterol. line, the pre-administration HMGCR inhibitor lovastatin abolished SLC13A2-mediated regeneration. Similarly, ACLY inhibition suppressed SLC13A2-promoted hepatocellular proliferation vivo. sum, this study demonstrates transported by acts an intermediate metabolite restore homeostasis suggesting potential drug target damage.

Language: Английский

Citations

0
Lipid profile and non-alcoholic fatty liver disease detected by ultrasonography: is systemic inflammation a necessary mediator? DOI Creative Commons
Wenzhen Li, Feng Wang, Zhimin Li

et al.

Annals of Medicine, Journal Year: 2025, Volume and Issue: 57(1)

Published: March 17, 2025

Aims To examine the relationship between lipid profile and non-alcoholic fatty liver (NAFL), compare predictive strengths of different indicators to NAFL, explore possible mechanisms.

Language: Английский

Citations

0
Biomarkers and potential therapeutic targets driving progression of non-alcoholic steatohepatitis to hepatocellular carcinoma predicted through transcriptomic analysis DOI Creative Commons
Huiqing Fan, Rong Wang,

Bin Wen

et al.

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: Dec. 4, 2024

Non-alcoholic steatohepatitis (NASH) is the most prevalent chronic liver condition globally, with potential progression to cirrhosis, and even hepatocellular carcinoma (HCC). The increasing prevalence of NASH underscores urgent need for advanced diagnostic therapeutic strategies. Despite its widespread impact, effective treatments prevent remain elusive, highlighting critical importance innovative molecular techniques in both diagnosis management this disease.

Language: Английский

Citations

0
LIX1L aggravates MASH-HCC progression by reprogramming of hepatic metabolism and microenvironment via CD36 DOI Creative Commons

Yingrong Leng,

Yanqiu Zhang, Cheng Yang

et al.

Pharmacological Research, Journal Year: 2024, Volume and Issue: unknown, P. 107567 - 107567

Published: Dec. 1, 2024

Limb expression 1-like protein (LIX1L) is an essential player in liver disorders, but its function metabolic dysfunction-associated steatohepatitis (MASH) and associated hepatocellular carcinoma (HCC) progression remains obscure. Here, we identify LIX1L as a key integrative regulator linking lipid metabolism inflammation, adipose tissue hepatic microenvironment, which promotes MASH progression. significantly upregulates patients, mouse models, palmitic acid-stimulated hepatocytes. Lix1l deletion inhibits accumulation, fibrosis well adipocyte differentiation by downregulating CD36, alleviating HCC mice. Mechanistically, stress PARP1-mediated poly-ADP-ribosylation of to increase stability RNA binding ability LIX1L. Subsequently, binds AU-rich element the 3'UTR CDS CD36 mRNA, thus mitigating mRNA decay. Furthermore, deficiency-mediated downregulation reprograms tumor-prone microenvironment with increased cytotoxic T lymphocytes reduced immunosuppressive cell proportions. These data indicate systematic pathogenesis underscore targeting PARP1/LIX1L/CD36 axis feasible strategy for treatment HCC.

Language: Английский

Citations

0