NOD-like receptors in the pathogenesis of metabolic (dysfunction)-associated fatty liver disease: Therapeutic agents targeting NOD-like receptors

Khanmohammadi, Shaghayegh; Ramos‐Molina, Bruno; Kuchay, Mohammad Shafi

doi:10.1016/j.dsx.2023.102788

Cited by 6 publications

(3 citation statements)

References 113 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, hepatic deletion of miR-122 in mice dramatically increases the production of proteins that promote inflammation and tumor growth. Similar findings are reported regarding the activity of miR-33b, expressed from an intron located inside sterol regulatory element-binding transcription factor 1 (SREBF-1), with anti-miR-33b oligonucleotide decreasing hepatic cholesterol and triglyceride accumulation in mice liver ( 7 ). From here comes the simplistic, mechanistic idea of blocking such miRNAs, for example, miR-33b, hoping to improve liver steatosis.…”

Section: Introductionsupporting

confidence: 77%

“…Impaired free fatty acid handling determines the generation of reactive oxygen species and toxic lipid metabolites such as diacylglycerols or ceramides, causing endoplasmic reticulum and oxidative stress with the activation of unfolded protein response. Excessive inflammatory cytokine production together with the accumulation of many other periportal inflammatory cells paves the way towards fibrosis and hepatocellular carcinoma ( 7 ).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Time for micro-RNAs in steatotic liver disease: a case–control study

Stoica,

Apostol,

Diculescu

et al. 2024

Front. Endocrinol.

View full text Add to dashboard Cite

One of the challenges of modern-day living is to resist the temptation of overfeeding and sedentariness and maintain a healthy body and mind. On a favorable genetic and epigenetic background, a high-fat diet combined with lack of physical exercise constitutes the foundation for severe metabolic disturbances including steatotic liver disease. In our case–control study, we had the aim of establishing the role of selected micro-RNAs—miR-122, miR-192, miR-33a, and miR-33b—as superior biomarkers for the diagnosis and prognosis of steatotic liver in a 36-patient cohort compared to 12 healthy controls. Initial results confirmed the decline in miR-122 expression as fatty liver is progressing. However, combinations of ΔmiRs, such as ΔmiR33a_192, ΔmiR33a_122, and ΔmiR33b_122, correlate with ultrasound steatosis grade (R2 = 0.78) while others such as ΔmiR33b_122 provide a high specificity and sensitivity in fatty liver disease with an area under the curve (AUC) of 0.85. Compared to classical biomarkers, micro-RNAs can be used for both diagnostic and prognostic purposes as their diminished expression in severe cases of steatosis is associated with higher risk of emerging hepatocellular carcinoma. Manipulating micro-RNAs through agomirs or antagomirs can be the answer to the yet unsolved problem of efficient therapy in MAFLD.

show abstract

Section: Introductionsupporting

confidence: 77%

Section: Introductionmentioning

confidence: 99%

Time for micro-RNAs in steatotic liver disease: a case–control study

Stoica,

Apostol,

Diculescu

et al. 2024

Front. Endocrinol.

View full text Add to dashboard Cite

show abstract

“…GO enrichment analysis of the differential genes revealed that cholesterol metabolism, acetyl coenzyme A metabolism and fatty acid metabolism were associated with HFD/STZ-induced steatohepatitis, indicating that HFD/STZ mice might have disorders of lipid metabolism. In metabolic-dysfunction-associated NALFD, inflammatory processes are important triggers that drive advanced fibrosis [ 46 ]. Our study found that cellular functions were enriched for TGF-β signaling after SZ-A administration.…”

Section: Discussionmentioning

confidence: 99%

Integration of Transcriptomics and Lipidomics Profiling to Reveal the Therapeutic Mechanism Underlying Ramulus mori (Sangzhi) Alkaloids for the Treatment of Liver Lipid Metabolic Disturbance in High-Fat-Diet/Streptozotocin-Induced Diabetic Mice

Wang,

Xu,

et al. 2023

Nutrients

View full text Add to dashboard Cite

Non-alcoholic fatty liver disease (NAFLD) is the most common liver disorder, with a global prevalence of 25%. Currently, there remains no approved therapy. Ramulus mori (Sangzhi) alkaloids (SZ-As), a novel natural medicine, have achieved comprehensive benefits in the treatment of type 2 diabetes; however, few studies have focused on its role in ameliorating hepatic lipid metabolic disturbance. Herein, the therapeutic effect and mechanism of SZ-As on a high-fat diet (HFD) combined with streptozotocin (STZ)-induced NAFLD mice were investigated via incorporating transcriptomics and lipidomics. SZ-As reduced body weight and hepatic lipid levels, restored pathological alternation and converted the blood biochemistry perturbations. SZ-A treatment also remarkedly inhibited lipogenesis and enhanced lipolysis, fatty acid oxidation and thermogenesis. Transcriptomics analysis confirmed that SZ-As mainly altered fatty acid oxidative metabolism and the TNF signaling pathway. SZ-As were further demonstrated to downregulate inflammatory factors and effectively ameliorate hepatic inflammation. Lipidomics analysis also suggested that SZ-As affected differential lipids including triglyceride (TG) and phosphatidylcholine (PC) expression, and the main metabolic pathways included glycerophospholipid, sphingomyelins and choline metabolism. Collectively, combined with transcriptomics and metabolomics data, it is suggested that SZ-As exert their therapeutic effect on NAFLD possibly through regulating lipid metabolism pathways (glycerophospholipid metabolism and choline metabolism) and increasing levels of PC and lysophosphatidylcholine (LPC) metabolites. This study provides the basis for more widespread clinical applications of SZ-As.

show abstract