Pan-PPAR agonist lanifibranor improves portal hypertension and hepatic fibrosis in experimental advanced chronic liver disease

Boyer‐Díaz, Zoe; Aristu-Zabalza, Peio; Andres-Rozas, Maria; Robert, Claude; Ortega‐Ribera, Martí; Fernández‐Iglesias, Anabel; Broqua, Pierre; Junien, Jean-Louis; Wettstein, Guillaume; Bosch, Jaime; Gracia‐Sancho, Jordi

doi:10.1016/j.jhep.2020.11.045

Cited by 102 publications

(67 citation statements)

References 35 publications

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“…Control rats received saline solution ( n = 5 per group). In addition, secondary biliary cirrhosis was induced in Sprague-Dawley male rats by ligation of the common bile duct (cBDL) for 4 weeks as described previously [ 18 ]. In sham animals, only surgery was performed without ligation of the common bile duct ( n = 5 per group).…”

Section: Methodsmentioning

confidence: 99%

Transcriptomic Profiling of the Liver Sinusoidal Endothelium during Cirrhosis Reveals Stage-Specific Secretory Signature

Manicardi

Fernández‐Iglesias

Abad-Jordà

et al. 2021

Cancers

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The poor prognosis of chronic liver disease (CLD) generates the need to investigate the evolving mechanisms of disease progression, thus disclosing therapeutic targets before development of clinical complications. Considering the central role of liver sinusoidal endothelial cells (LSECs) in pre-neoplastic advanced CLD, the present study aimed at investigating the progression of CLD from an endothelial holistic perspective. RNAseq defined the transcriptome of primary LSECs isolated from three pre-clinical models of advanced CLD, during the progression of the disease, and from fresh human cirrhotic tissue. At each stage of the disease, the effects of LSECs secretome on neighboring cells and proteomic analysis of LSECs-derived extracellular vesicles (EVs) were also determined. CLD was associated with deep common modifications in the transcriptome of LSECs in the pre-clinical models. Pathway enrichment analysis showed predominance of genes related with pro-oncogenic, cellular communication processes, and EVs biogenesis during CLD progression. Crosstalk experiments revealed endothelial EVs as potent angiocrine effectors. The proteome of LSECs EVs showed stage-specific signatures, including over-expression of tropomyosin-1. Proof-of-principle experiments treating cirrhotic HSCs with recombinant tropomyosin-1 suggested de-activating effects. Our data provide the basis for discovering novel biomarkers and therapeutic targets for new disease-modifying treatments for patients with advanced CLD.

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Section: Methodsmentioning

confidence: 99%

Transcriptomic Profiling of the Liver Sinusoidal Endothelium during Cirrhosis Reveals Stage-Specific Secretory Signature

Manicardi

Fernández‐Iglesias

Abad-Jordà

et al. 2021

Cancers

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“…In addition, saroglitazar improved insulin resistance and NASH in an animal model of NAFLD [118]. A pan-PARR agonist, lanifibranor, improved all histologic features of NASH in experimental models [119,120].…”

Section: Pharmacologic Treatmentsmentioning

confidence: 98%

Non-Alcoholic Fatty Liver Disease in Lean and Non-Obese Individuals: Current and Future Challenges

et al. 2021

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Non-alcoholic fatty liver disease (NAFLD), which approximately affects a quarter of the world’s population, has become a major public health concern. Although usually associated with excess body weight, it may also affect normal-weight individuals, a condition termed as lean/non-obese NAFLD. The prevalence of lean/non-obese NAFLD is around 20% within the NAFLD population, and 5% within the general population. Recent data suggest that individuals with lean NAFLD, despite the absence of obesity, exhibit similar cardiovascular- and cancer-related mortality compared to obese NAFLD individuals and increased all-cause mortality risk. Lean and obese NAFLD individuals share several metabolic abnormalities, but present dissimilarities in genetic predisposition, body composition, gut microbiota, and susceptibility to environmental factors. Current treatment of lean NAFLD is aimed at improving overall fitness and decreasing visceral adiposity, with weight loss strategies being the cornerstone of treatment. Moreover, several drugs including PPAR agonists, SGLT2 inhibitors, or GLP-1 receptor agonists could also be useful in the management of lean NAFLD. Although there has been an increase in research regarding lean NAFLD, there are still more questions than answers. There are several potential drugs for NAFLD therapy, but clinical trials are needed to evaluate their efficacy in lean individuals.

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“…Celecoxib ( 25 – 29 , 67 ) , aspirin ( 30 , 31 ) , etanercept ( 32 ) , curcumin ( 33 – 39 ) , kahweol ( 40 , 41 ) , pentoxifylline ( 42 , 68 ) , diosmin ( 42 – 44 ) , glycyrrhizin arginine salt ( 45 ) , statins ( 18 , 19 , 46 – 50 ) , emricasan ( 20 – 22 , 51 , 69 ) and lanifibranor ( 52 ) and formayl receptor 2 agonist—WKYMVm ( 53 ).…”

Section: Resultsmentioning

confidence: 99%

Novel Anti-inflammatory Treatments in Cirrhosis. A Literature-Based Study

et al. 2021

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Liver cirrhosis is a disease characterised by multiple complications and a poor prognosis. The prevalence is increasing worldwide. Chronic inflammation is ongoing in liver cirrhosis. No cure for the inflammation is available, and the current treatment of liver cirrhosis is only symptomatic. However, several different medical agents have been suggested as potential healing drugs. The majority are tested in rodents, but few human trials are effectuated. This review focuses on medical agents described in the literature with supposed alleviating and curing effects on liver cirrhosis. Twelve anti-inflammatory, five antioxidative, and three drugs with effects on gut microflora and the LPS pathway were found. Two drugs not categorised by the three former categories were found in addition. In total, 42 rodent studies and seven human trials were found. Promising effects of celecoxib, aspirin, curcumin, kahweol, pentoxifylline, diosmin, statins, emricasan, and silymarin were found in cirrhotic rodent models. Few indices of effects of etanercept, glycyrrhizin arginine salt, and mitoquinone were found. Faecal microbiota transplantation is in increasing searchlight with a supposed potential to alleviate cirrhosis. However, human trials are in demand to verify the findings in this review.

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Pan-PPAR agonist lanifibranor improves portal hypertension and hepatic fibrosis in experimental advanced chronic liver disease

Cited by 102 publications

References 35 publications

Transcriptomic Profiling of the Liver Sinusoidal Endothelium during Cirrhosis Reveals Stage-Specific Secretory Signature

Transcriptomic Profiling of the Liver Sinusoidal Endothelium during Cirrhosis Reveals Stage-Specific Secretory Signature

Non-Alcoholic Fatty Liver Disease in Lean and Non-Obese Individuals: Current and Future Challenges

Novel Anti-inflammatory Treatments in Cirrhosis. A Literature-Based Study

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