Saroglitazar Deactivates the Hepatic LPS/TLR4 Signaling Pathway and Ameliorates Adipocyte Dysfunction in Rats with High-Fat Emulsion/LPS Model-Induced Non-alcoholic Steatohepatitis

Hassan, Noha F.; Nada, Somaia A.; Hassan, Azza; El-Ansary, Mona R; Al-Shorbagy, Muhammad Y.; Abdelsalam, Rania M.

doi:10.1007/s10753-019-00967-6

Cited by 39 publications

(27 citation statements)

References 71 publications

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“…In addition, we found that compared with HFD alone, CSP treatment downregulated PPARγ in the liver (Fig 3E). Previous studies have shown that PPARγ can inhibit activation of HSCs and is present at a low level in the liver in NASH [44][45][46]. The above results suggest that CSP supplementation may contribute to the progression from obesity to NASH.…”

Section: Plos Onesupporting

confidence: 51%

Polysaccharides isolated from Cordyceps Sinensis contribute to the progression of NASH by modifying the gut microbiota in mice fed a high-fat diet

et al. 2020

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Various dietary fibers are considered to prevent obesity by modulating the gut microbiota. Cordyceps sinensis polysaccharide (CSP) is a soluble dietary fiber known to have protective effects against obesity and related diseases, but whether these effects induce any side effects remains unknown. The function and safety of CSP were tested in high-fat diet (HFD)-feding C57BL/6J mice. The results revealed that even though CSP supplementation could prevent an increase in body weight, it aggravated liver fibrosis and steatosis as evidenced by increased inflammation, lipid metabolism markers, insulin resistance (IR) and alanine aminotransferase (ALT) in HFD-induced obesity. 16S rDNA gene sequencing was used to analyze the gut microbiota composition, and the relative abundance of the Actinobacteria phylum, including the Olsenella genus, was significantly higher in CSP-treated mice than in HFD-fed mice. CSP supplementation may increase the proportion of Actinobacteria, which can degrade CSP. The high level of Actinobacteria aggravated the disorder of the intestinal flora and contributed to the progression from obesity to nonalcoholic steatohepatitis (NASH) and related diseases.

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Section: Plos Onesupporting

confidence: 51%

Polysaccharides isolated from Cordyceps Sinensis contribute to the progression of NASH by modifying the gut microbiota in mice fed a high-fat diet

et al. 2020

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“…In a rapid rat model of NASH induced by high-fat emulsion and small doses of LPS, saroglitazar improved adipocyte dysfunction through increased plasma adiponectin. In the liver, saroglitazar induced a decrease in TLR4 signaling upon LPS administration, with reduced NF-κB, TLR4, and TGFβ, which suggests a role of saroglitazar in response to gut endotoxins [403]. Saroglitazar also reduces thioacetamide-induced liver fibrosis in rats and decreases leptin, TGF-β, and platelet-derived growth factor (PDGF-BB) in the liver [404].…”

Section: Pparα and γ Dual Agonist Saroglitazarmentioning

confidence: 93%

Peroxisome Proliferator-Activated Receptors and Their Novel Ligands as Candidates for the Treatment of Non-Alcoholic Fatty Liver Disease

Fougerat

Montagner

Loiseau

et al. 2020

Cells

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Non-alcoholic fatty liver disease (NAFLD) is a major health issue worldwide, frequently associated with obesity and type 2 diabetes. Steatosis is the initial stage of the disease, which is characterized by lipid accumulation in hepatocytes, which can progress to non-alcoholic steatohepatitis (NASH) with inflammation and various levels of fibrosis that further increase the risk of developing cirrhosis and hepatocellular carcinoma. The pathogenesis of NAFLD is influenced by interactions between genetic and environmental factors and involves several biological processes in multiple organs. No effective therapy is currently available for the treatment of NAFLD. Peroxisome proliferator-activated receptors (PPARs) are nuclear receptors that regulate many functions that are disturbed in NAFLD, including glucose and lipid metabolism, as well as inflammation. Thus, they represent relevant clinical targets for NAFLD. In this review, we describe the determinants and mechanisms underlying the pathogenesis of NAFLD, its progression and complications, as well as the current therapeutic strategies that are employed. We also focus on the complementary and distinct roles of PPAR isotypes in many biological processes and on the effects of first-generation PPAR agonists. Finally, we review novel and safe PPAR agonists with improved efficacy and their potential use in the treatment of NAFLD.

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“…80 Saroglitazar also led to a significant change in adipokine levels, resulting in a substantial decrease in serum leptin and TNF-α level. 80 In NASH models, saroglitazar reduced hepatic steatosis, inflammation, ballooning, and fibrosis. 81 It also reduced liver enzymes and the expression of inflammatory and fibrosis biomarkers.…”

Section: Saroglitazarmentioning

confidence: 99%

“…78,79 Saroglitazar in mice has shown to ameliorate NASH through down-regulation of the hepatic lipopolysaccharide/ toll-like receptor-4 pathway and inhibition of adipocyte dysfunction. 80 Saroglitazar prevents weight gain, normalizes liver enzymes, improves insulin resistance, dyslipidemia, and hepatic inflammation in NASH mice. 80 Saroglitazar also led to a significant change in adipokine levels, resulting in a substantial decrease in serum leptin and TNF-α level.…”

Section: Saroglitazarmentioning

confidence: 99%

“…80 Saroglitazar prevents weight gain, normalizes liver enzymes, improves insulin resistance, dyslipidemia, and hepatic inflammation in NASH mice. 80 Saroglitazar also led to a significant change in adipokine levels, resulting in a substantial decrease in serum leptin and TNF-α level. 80 In NASH models, saroglitazar reduced hepatic steatosis, inflammation, ballooning, and fibrosis.…”

Section: Saroglitazarmentioning

confidence: 99%

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Drugs for Non-alcoholic Steatohepatitis (NASH): Quest for the Holy Grail

Sharma¹,

Premkumar²,

Kulkarni³

et al. 2020

Journal of Clinical and Translational Hepatology

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Nonalcoholic fatty liver disease (NAFLD) is a global epidemic that is likely to become the most common cause of chronic liver disease in the next decade, worldwide. Though numerous drugs have been evaluated in clinical trials, most of them have returned inconclusive results and shown poorly-tolerated adverse effects. None of the drugs have been approved by the Food and Drug Administration for treating biopsy-proven non-alcoholic steatohepatitis (NASH). Vitamin E and pioglitazone have been extensively used in treatment of biopsy-proven nondiabetic NASH patients. Although some amelioration of inflammation has been seen, these drugs did not improve the fibrosis component of NASH. Therefore, dietary modification and weight reduction have remained the cornerstone of treatment of NASH; moreover, they have shown to improve histological activity as well as fibrosis. The search for an ideal drug or ‘Holy Grail’ within this landscape of possible agents continues, as weight reduction is achieved only in less than 10% of patients. In this current review, we summarize the drugs for NASH which are under investigation, and we provide a critical analysis of their up-to-date results and outcomes.

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Saroglitazar Deactivates the Hepatic LPS/TLR4 Signaling Pathway and Ameliorates Adipocyte Dysfunction in Rats with High-Fat Emulsion/LPS Model-Induced Non-alcoholic Steatohepatitis

Cited by 39 publications

References 71 publications

Polysaccharides isolated from Cordyceps Sinensis contribute to the progression of NASH by modifying the gut microbiota in mice fed a high-fat diet

Polysaccharides isolated from Cordyceps Sinensis contribute to the progression of NASH by modifying the gut microbiota in mice fed a high-fat diet

Peroxisome Proliferator-Activated Receptors and Their Novel Ligands as Candidates for the Treatment of Non-Alcoholic Fatty Liver Disease

Drugs for Non-alcoholic Steatohepatitis (NASH): Quest for the Holy Grail

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