saroglitazar and Non-alcoholic-Fatty-Liver-Disease

Fibrosis impacts long-term outcomes among patients with nonalcoholic fatty liver disease (NAFLD). Due to well-documented flaws associated with liver biopsy, there has been a recent emphasis on prioritizing noninvasive testing over liver biopsy for the assessment of fibrosis.. A comprehensive systematic review and frequentist random effects network meta-analysis was performed among randomized controlled trials reporting pharmacologic intervention in NAFLD. The primary endpoint was the absolute change in liver stiffness measurement (LSM) via elastography. Secondary endpoints included changes in noninvasive serologic tests including APRI, fibrosis-4 index, NAFLD fibrosis score, enhanced liver fibrosis (ELF) and FibroTest (FibroSure in the USA).. Forty-five randomized controlled trials enrolling 6932 patients were identified for this network meta-analysis. Across the primary endpoint, firsocostat, semaglutide, montelukast, cilofexor plus firsocostat, obeticholic acid and diacerein (change in LSM via vibration controlled transient elastography), in addition to lubiprostone and pemafibrate (change in LSM via magnetic resonance elastography) were found to be the most effective and statistically significant treatment interventions. Similarly, the following interventions were determined to be most effective as compared to placebo among secondary endpoints: saroglitazar, lubiprostone, and obeticholic acid (change in APRI); saroglitazar, semaglutide, firsocostat and cilofexor plus firsocostat (change in ELF); obeticholic acid and belapectin [change in FibroTest/FibroSure].. This is the first systematic review and network meta-analysis reporting pharmacologic efficacy in the progression of fibrosis based on noninvasive testing among patients with NAFLD. Semaglutide, obeticholic acid, firsocostat, cilofexor plus firsocostat and lubiprostone were found to be the most effective treatments based on their consistent efficacy reproduced across multiple endpoints, both via elastography and noninvasive blood tests.

Topics: Humans; Liver Cirrhosis; Lubiprostone; Network Meta-Analysis; Non-alcoholic Fatty Liver Disease; Randomized Controlled Trials as Topic

Cardiovascular disease is the leading cause of mortality in nonalcoholic fatty liver disease (NAFLD). The aim of this study was to evaluate the effects of saroglitazar, a dual peroxisome proliferator-activated receptor α/γ agonist, on serum lipids in patients with NAFLD.. A total of 221 patients (saroglitazar, 130; placebo, 91) with NAFLD from phase 2 and 3 double-blinded placebo-controlled randomized clinical trials were pooled to assess the impact of saroglitazar magnesium 4 mg on traditional lipids, very low density lipoprotein cholesterol (VLDL-C), and small dense LDL-C (sdLDL-C). Change from baseline in lipid parameters was performed by using analysis of covariance including treatment as fixed effect and baseline value, diabetes, hypertension, and statin use as covariates.. Treatment with saroglitazar significantly improved total cholesterol (-17 mg/dL, 95% confidence interval [CI], -24 to 9; P < .001), triglyceride (-45 mg/dL, 95% CI, -60 to 31; P < .001), low-density lipoprotein cholesterol (-8 mg/dL, 95% CI, -15 to -1; P = .01), and VLDL-C (-8 mg/dL, -14 to -3; P < .001). Saroglitazar improved serum lipids as early as 4-6 weeks of initiation of therapy, and these effects persisted for duration of therapy. Saroglitazar also improved the highly atherogenic sdLDL-C (-10 mg/dL, -17 to -2; P = .01). In subgroup analysis of patients with either diabetes or hypertension, saroglitazar significantly improved serum lipids.. Saroglitazar improved the serum atherogenic lipoprotein profile in patients with NAFLD, irrespective of comorbid conditions and statin use. Saroglitazar has the potential to not only positively affect liver disease but also reduce cardiovascular risk in patients with NAFLD. (Trials registrations: CTRI 2015/10/006236, CTRI 173300410A0106, NCT03863574, and NCT03061721).

Topics: Cholesterol; Diabetes Mellitus, Type 2; Dyslipidemias; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypertension; Non-alcoholic Fatty Liver Disease; PPAR alpha; PPAR-gamma Agonists; Triglycerides

To undertake a network meta-analysis to compare the relative efficacy of a dual peroxisome proliferator-activated receptor (PPAR)α and PPARγ agonist, glucagon-like peptide-1 receptor agonists (GLP-1RAs) and metformin in patients with non-alcoholic fatty liver disease (NAFLD).. Electronic databases, including Embase®, PubMed® and The Cochrane Library, were searched systematically for eligible studies from inception to 20 July 2022. Randomized controlled trials (RCTs) that investigated aspartate aminotransferase, alanine aminotransferase (ALT) and triglyceride levels were considered for inclusion. Data were extracted using a standardized data collection table. A network meta-analysis was performed. Relative risk and 95% confidence interval were calculated for continuous data and. A total of 22 RCTs involving 1698 patients were eligible for inclusion in the analysis. Both direct analysis and indirect analysis showed that saroglitazar was significantly superior to GLP-1RAs in improving ALT levels. Metformin improved ALT levels, but the effect was not as good as saroglitazar.. Saroglizatar was the most effective drug for improving NAFLD.INPLASY registration number: INPLASY202340066.

Topics: Glucagon-Like Peptide-1 Receptor; Humans; Metformin; Network Meta-Analysis; Non-alcoholic Fatty Liver Disease; Peroxisome Proliferator-Activated Receptors

Non-alcoholic fatty liver disease (NAFLD) affects one-third of the population worldwide, of which a substantial number of patients suffer from non-alcoholic steatohepatitis (NASH). NASH is a severe condition characterized by steatosis and concomitant liver inflammation and fibrosis, for which no drug is yet available. NAFLD is also generally conceived as the hepatic manifestation of the metabolic syndrome. Consequently, well-established drugs that are indicated for the treatment of type 2 diabetes and hyperlipidemia are thought to exert effects that alleviate the pathological features of NASH. One class of these drugs targets peroxisome proliferator-activated receptors (PPARs), which are nuclear receptors that play a regulatory role in lipid metabolism and inflammation. Therefore, PPARs are now also being investigated as potential anti-NASH druggable targets. In this paper, we review the mechanisms of action and physiological functions of PPARs and discuss the position of the different PPAR agonists in the therapeutic landscape of NASH. We particularly focus on the PPAR agonists currently under evaluation in clinical phase II and III trials. Preclinical strategies and how refinement and optimization may improve PPAR-targeted anti-NASH drug testing are also discussed. Finally, potential caveats related to PPAR agonism in anti-NASH therapy are stipulated.

Topics: Chalcones; Diabetes Mellitus, Type 2; Drug Development; Fatty Liver; Humans; Hypoglycemic Agents; Inflammation; Liver; Non-alcoholic Fatty Liver Disease; Peroxisome Proliferator-Activated Receptors; Phenylpropionates; Pioglitazone; Propionates; Pyrroles

Saroglitazar, a novel dual peroxisome proliferator activated receptor (PPAR) agonist, in clinical trials, has shown an improvement in lipid and glycemic parameters through the PPAR-α and γ agonist actions, respectively. It was granted marketing authorization in India in 2013 for diabetic dyslipidemia. This review was conducted to summarize the effects of Saroglitazar in patients with diabetic dyslipidemia in real world clinical studies conducted after marketing authorization in India.. In this review, we selected real world clinical studies of Saroglitazar published as manuscripts and abstracts presented at scientific conferences. In all these studies, patients with diabetic dyslipidemia were treated with Saroglitazar 4 mg once daily for at least 12 weeks and different lipid and glycemic parameters were measured at the baseline and end of the study.. In 18 selected studies (5 published manuscripts and 13 abstracts), a total of 5824 patients with diabetic dyslipidemia were prescribed Saroglitazar 4 mg for a duration ranging from 12 to 58 weeks. Across all the studies, mean age of patients ranged from 49.6 to 59.1 years and the proportion of female patients ranged from 22% to 42%. Across all the studies, there was a consistent mean reduction in triglyceride levels (~ 45% to 62%), total cholesterol levels (~ 17% to 26%), non-high-density lipoprotein cholesterol levels (~ 21% to 36%), low-density lipoprotein cholesterol levels (~ 11% to 27%), and glycosylated hemoglobin levels (~ 0.7% to 1.6%) with an increase in mean high-density lipoprotein cholesterol levels (up to 9%) from baseline to end of the study. Saroglitazar also improved alanine aminotransferase levels and fatty liver (evaluated by FibroScan™) in non-alcoholic fatty liver disease patients with diabetic dyslipidemia. Body weight remained unchanged and no significant adverse events (AEs) were reported in the studies.. Saroglitazar effectively improved lipid and glycemic parameters without significant AEs in patients with diabetic dyslipidemia in real-world clinical studies of up to 58 weeks duration.

Topics: Biomarkers; Blood Glucose; Diabetes Mellitus, Type 2; Dyslipidemias; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Hypolipidemic Agents; India; Lipids; Male; Middle Aged; Non-alcoholic Fatty Liver Disease; Phenylpropionates; PPAR alpha; PPAR gamma; Pyrroles; Signal Transduction; Time Factors; Treatment Outcome

NAFLD is characterized by insulin resistance and dysregulated lipid and glucose metabolism. Saroglitazar, a dual peroxisome proliferator activated receptor-α/γ agonist, improves insulin sensitivity, and lipid and glycemic parameters. Saroglitazar improved NASH histology in animal studies. In this randomized controlled clinical trial, we evaluated the efficacy and safety of saroglitazar in patients with NAFLD/NASH.. Saroglitazar 4 mg significantly improved ALT, LFC, insulin resistance, and atherogenic dyslipidemia in participants with NAFLD/NASH. (ClinicalTrials.gov identifier: NCT03061721.).

Topics: Adipose Tissue; Adult; Alanine Transaminase; Alkaline Phosphatase; Aspartate Aminotransferases; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Cholesterol, VLDL; Double-Blind Method; Elasticity Imaging Techniques; Female; gamma-Glutamyltransferase; Humans; Insulin Resistance; Liver; Magnetic Resonance Imaging; Male; Middle Aged; Non-alcoholic Fatty Liver Disease; Phenylpropionates; PPAR alpha; PPAR gamma; Pyrroles; Triglycerides

Saroglitazar is a novel PPAR-α/γ agonist with predominant PPAR-α activity. In various preclinical models, saroglitazar has been shown to prevent & reverse symptoms of NASH. In view of these observations, and the fact that NASH is a progressive disease leading to HCC, we hypothesized that saroglitazar may prevent the development of HCC in rodents.. HCC was induced in C57BL/6 mice by a single intraperitoneal injection of 25 mg/kg diethylnitrosamine (DEN) at the age of 4 weeks and then feeding the animal a choline-deficient, L-amino acid- defined, high-fat diet (CDAHFD) for the entire study duration. Eight weeks after initiation of CDAHFD, saroglitazar (1 and 3 mg/kg) treatment was started and continued for another 27 weeks.. Saroglitazar treatment significantly reduced the liver injury markers (serum ALT and AST), reversed hepatic steatosis and decreased the levels of pro-inflammatory cytokines like TNF-α in liver. It also resulted in a marked increase in serum adiponectin and osteopontin levels. All disease control animals showed hepatic tumors, which was absent in saroglitazar (3 mg/kg)- treatment group indicating 100% prevention of hepatic tumorigenesis. This is the first study demonstrating a potent PPARα agonist causing suppression of liver tumors in rodents, perhaps due to a strong anti-NASH activity of Saroglitazar that overrides its rodent-specific peroxisome proliferation activity.. The data reveals potential of saroglitazar for chemoprevention of hepatocellular carcinoma in patients with NAFLD/NASH.

Topics: Amino Acids; Animals; Carcinoma, Hepatocellular; Choline; Diet, High-Fat; Diethylnitrosamine; Disease Models, Animal; Injections, Intraperitoneal; Liver; Liver Neoplasms; Mice; Mice, Inbred C57BL; Non-alcoholic Fatty Liver Disease; Peroxisome Proliferator-Activated Receptors

NAFLD is common after liver transplantation (LT) and is associated with an increased metabolic burden. Currently, there is a paucity of investigations into the treatment of post-LT NAFLD. In the present study, we evaluated the safety and efficacy of saroglitazar, a novel dual peroxisome proliferator-associated receptor α/γ agonist, on the treatment of post-LT NAFLD and metabolic burden. This is a phase 2A, single-center, open-label, single-arm study in which patients with post-LT NAFLD received saroglitazar magnesium 4 mg daily for 24 weeks. NAFLD was defined by a controlled attenuation parameter ≥264 dB/m. The primary endpoint was the reduction in liver fat as measured by MRI proton density fat fraction (MRI-PDFF). Secondary MRI-based metabolic endpoints included visceral adipose tissue, abdominal subcutaneous adipose tissue volumes, muscle fat infiltration, and fat-free muscle volume. Saroglitazar treatment led to a reduction in MRI-PDFF from 10.3±10.5% at baseline to 8.1±7.6%. A relative 30% reduction from baseline MRI-PDFF value was noted in 47% of all patients and 63% of patients with baseline MRI-PDFF >5%. Reduction in serum alkaline phosphatase was an independent predictor of MRI-PDFF response. Saroglitazar did not decrease fat-free muscle volume nor increase muscle fat infiltration, but did lead to a mild increase in visceral adipose tissue and abdominal subcutaneous adipose tissue. The study drug was well tolerated and a mild nonsignificant increase in serum creatinine was noted. Saroglitazar did not affect the weight. The study provides preliminary data demonstrating the safety and metabolic benefits of saroglitazar in LT recipients and underscores the importance of future studies to establish its efficacy after LT.

Topics: Humans; Liver; Liver Transplantation; Magnetic Resonance Imaging; Non-alcoholic Fatty Liver Disease; Phenylpropionates

Peroxisome proliferator-activated receptors (PPARs) are nuclear receptor-type transcription factors that consist of three subtypes (α, γ, and β/δ) with distinct functions and PPAR dual/pan agonists are expected to be the next generation of drugs for metabolic diseases. Saroglitazar is the first clinically approved PPARα/γ dual agonist for treatment of diabetic dyslipidemia and is currently in clinical trials to treat non-alcoholic fatty liver disease (NAFLD); however, the structural information of its interaction with PPARα/γ remains unknown. We recently revealed the high-resolution co-crystal structure of saroglitazar and the PPARα-ligand binding domain (LBD) through X-ray crystallography, and in this study, we report the structure of saroglitazar and the PPARγ-LBD. Saroglitazar was located at the center of "Y"-shaped PPARγ-ligand-binding pocket (LBP), just as it was in the respective region of PPARα-LBP. Its carboxylic acid was attached to four amino acids (Ser289/His323/His449/Thr473), which contributes to the stabilization of Activating Function-2 helix 12, and its phenylpyrrole moiety was rotated 121.8 degrees in PPARγ-LBD from that in PPARα-LBD to interact with Phe264. PPARδ-LBD has the consensus four amino acids (Thr253/His287/His413/Tyr437) towards the carboxylic acids of its ligands, but it seems to lack sufficient space to accept saroglitazar because of the steric hindrance between the Trp228 or Arg248 residue of PPARδ-LBD and its methylthiophenyl moiety. Accordingly, in a coactivator recruitment assay, saroglitazar activated PPARα-LBD and PPARγ-LBD but not PPARδ-LBD, whereas glycine substitution of either Trp228, Arg248, or both of PPARδ-LBD conferred saroglitazar concentration-dependent activation. Our findings may be valuable in the molecular design of PPARα/γ dual or PPARα/γ/δ pan agonists.

Topics: Binding Sites; Crystallography, X-Ray; Diabetes Mellitus, Type 2; Dyslipidemias; Humans; Hypolipidemic Agents; Lipid Metabolism; Non-alcoholic Fatty Liver Disease; Phenylpropionates; PPAR alpha; PPAR gamma; Protein Domains; Pyrroles; Recombinant Proteins

Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) have become significant global health concerns. In the present study, we aimed to investigate the effects of saroglitazar, a dual PPARα/γ agonist, fenofibrate, a PPAR-α agonist, and pioglitazone, a PPAR-γ agonist on an animal model of NASH.. Male Wistar rats were fed a high-fat (HF) emulsion via gavage for 7 weeks to induce NASH. The HF-treated rats were grouped into four groups to receive saroglitazar, pioglitazone, fenofibrate, or vehicle. We measured body and liver weight, liver enzymes, serum levels of adiponectin and leptin. We also performed histopathological examinations and gene expression analysis of interleukin 6 (IL-6), tumor necrosis factor-alpha (TNF- α), transforming growth factor-beta (TGF-β), and monocyte chemoattractant protein 1 (MCP-1).. Body weight was markedly normalized by both saroglitazar and fenofibrate, while the liver index only decreased significantly with saroglitazar. Saroglitazar corrected ALT, AST, leptin, and adiponectin levels better than pioglitazone and fenofibrate. All PPAR agonists significantly attenuated the upregulation of the proinflammatory and TGF-β genes, which correlated with the improved steatosis, inflammation of liver tissue, and fibrotic lesions.. As documented by our results, the dual activation of PPARα/γ by saroglitazar could effectively improve steatosis, fibrosis, and aspects of necro-inflammation in the HF-induced NASH model more than fenofibrate and pioglitazone, and it can be more beneficial in the management of NASH.

Topics: Alanine Transaminase; Animals; Aspartate Aminotransferases; Cytokines; Disease Models, Animal; Gene Expression Regulation; Liver; Liver Cirrhosis; Male; Non-alcoholic Fatty Liver Disease; Phenylpropionates; PPAR alpha; PPAR gamma; Pyrroles; Rats, Wistar

Topics: Humans; Non-alcoholic Fatty Liver Disease; Phenylpropionates; Pyrroles

Topics: Humans; Non-alcoholic Fatty Liver Disease; Peroxisome Proliferator-Activated Receptors; Phenylpropionates; Pyrroles

Topics: Humans; Non-alcoholic Fatty Liver Disease; Phenylpropionates; Pyrroles

Topics: Diabetes Mellitus; Dyslipidemias; Elasticity Imaging Techniques; Humans; Liver; Non-alcoholic Fatty Liver Disease; Phenylpropionates; Pyrroles; Transaminases

Insulin resistance and hepatic lipid accumulation constitute the metabolic underpinning of nonalcoholic steatohepatitis (NASH). We tested the hypothesis that saroglitazar, a PPAR α/γ agonist would improve NASH in the diet-induced animal model of NAFLD. Mice received chow diet and normal water (CDNW) or high fat western diet and ad lib sugar water (WDSW). After 12 weeks, WDSW fed mice were randomized to receive (1) WDSW alone, (2) WDSW + vehicle, (3) WDSW + pioglitazone or (4) WDSW + saroglitazar for an additional 12 weeks. Compared to mice on WDSW and vehicle controls, mice receiving WDSW + saroglitazar had lower weight, lower HOMA-IR, triglycerides, total cholesterol, and ALT. Saroglitazar improved steatosis, lobular inflammation, hepatocellular ballooning and fibrosis stage. NASH resolved in all mice receiving saroglitazar. These effects were at par with or superior to pioglitazone. Molecular analyses confirmed target engagement and reduced oxidative stress, unfolded protein response and fibrogenic signaling. Transcriptomic analysis further confirmed increased PPAR-target expression and an anti-inflammatory effect with saroglitazar. Lipidomic analyses demonstrated that saroglitazar also reduced triglycerides, diglycerides, sphingomyelins and ceramides. These preclinical data provide a strong rationale for developing saroglitazar for the treatment of NASH in humans.

Topics: Animals; Diet, High-Fat; Disease Models, Animal; Dyslipidemias; Endoplasmic Reticulum Stress; Gene Expression Profiling; Insulin Resistance; Liver; Liver Cirrhosis; Metabolomics; Non-alcoholic Fatty Liver Disease; Phenylpropionates; PPAR alpha; PPAR gamma; Pyrroles; Signal Transduction

Saroglitazar, a dual peroxisome proliferator activated receptor α/γ agonist, approved for diabetic dyslipidemia (DD), is potential therapeutic option for non-alcoholic fatty liver disease (NAFLD). This prospective, observational, real-world study aimed to determine efficacy and safety of Saroglitazar in patients with NAFLD and DD. We included patients with DD and NAFLD who received Saroglitazar 4 mg once daily for 24 weeks. Blood investigations, liver stiffness measurement (LSM) and controlled attenuation parameter (CAP) (FibroScan) were compared at baseline and 24 weeks. Of 163 patients screened, 107 were included, and 101 completed 24 weeks treatment (mean age 50.4 ± 12.3 years, 78.5% males, mean body mass index 28.8 ± 4.2). After 24 weeks, alanine transaminase (ALT) reduced significantly from 94 (47-122) to 39 (31-49) (p < 0.0001) and aspartate aminotransferase (AST) (U/L) from 89 (43-114) to 37 (30-47) (p < 0.0001) and LSM (kPa) from 8.4 (7.1-9.3) to 7.5 (6.4-8.4) (p = 0.0261). CAP, glycated hemoglobin and lipid parameters also improved significantly. On linear regression, there was significant association between percent change in ALT and AST with TG reduction after treatment (p = 0.024 and 0.037 respectively).We conclude that Saroglitazar leads to significant improvement in transaminases, LSM, and CAP in NAFLD patients with DD.

Topics: Alanine Transaminase; Aspartate Aminotransferases; Diabetes Mellitus, Type 2; Dyslipidemias; Female; Humans; Liver; Male; Middle Aged; Non-alcoholic Fatty Liver Disease; Phenylpropionates; Prospective Studies; Pyrroles; Regression Analysis

The most epidemic liver disorder non-alcoholic steatohepatitis (NASH) is characterized by hepatic steatosis and inflammation with hepatocellular damage. Recently, it is predictable to be the extensive cause for liver transplantation. The absence of an approved therapeutic agent for NASH is the reason for investigating saroglitazar (SAR) which showed promising effects as a dual PPAR-α/γ agonist in recent studies on NASH. Here, we aimed to investigate the effect of SAR on NASH induced in rats by the administration of high-fat emulsion (HFE) and small doses of lipopolysaccharides (LPS) for 5 weeks. Rats were divided into three groups: negative control group (saline and standard rodent chow), model group (HFE(10 ml/kg/day, oral gavage) + LPS(0.5 mg/kg/week, i.p)), and SAR-treated group (HFE(10 ml/kg/day, oral gavage) + LPS(0.5 mg/kg/week, i.p.) + SAR(4 mg/kg/day, oral gavage) starting at week 3.Treatment with SAR successfully ameliorated the damaging effects of HFE with LPS, by counteracting body weight gain and biochemically by normalization of liver function parameters activity, glucose, insulin, homeostasis model of assessment (HOMA-IR) score, lipid profile levels, and histopathological examination. Significant changes in adipokine levels were perceived, resulting in a significant decline in serum leptin and tumor necrosis factor-α (TNF-α) level concurrent with adiponectin normalization. The positive effects observed for SAR on NASH are due to the downregulation of the LPS/TLR4 pathway, as indicated by the suppression of hepatic Toll-like receptor 4 (TLR4), NF-κB, TNF-α, and transforming growth factor-β1 (TGF-β1) expression. In conclusion, this work verified that SAR ameliorates NASH through deactivation of the hepatic LPS/TLR4 pathway and inhibition of adipocyte dysfunction.

Topics: Adipocytes; Animals; Down-Regulation; Lipopolysaccharides; Liver; Non-alcoholic Fatty Liver Disease; Phenylpropionates; Pyrroles; Rats; Signal Transduction; Toll-Like Receptor 4

Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) are common clinico-pathological conditions that affect millions of patients worldwide. In this study, the efficacy of saroglitazar, a novel PPARα/γ agonist, was assessed in models of NAFLD/NASH.. HepG2 cells treated with palmitic acid (PA;0.75 mM) showed decreased expression of various antioxidant biomarkers (SOD1, SOD2, glutathione peroxidase and catalase) and increased expression of inflammatory markers (TNFα, IL1β and IL6). These effects were blocked by saroglitazar, pioglitazone and fenofibrate (all tested at 10μM concentration). Furthermore, these agents reversed PA-mediated changes in mitochondrial dysfunction, ATP production, NFkB phosphorylation and stellate cell activation in HepG2 and HepG2-LX2 Coculture studies. In mice with choline-deficient high-fat diet-induced NASH, saroglitazar reduced hepatic steatosis, inflammation, ballooning and prevented development of fibrosis. It also reduced serum alanine aminotransferase, aspartate aminotransferase and expression of inflammatory and fibrosis biomarkers. In this model, the reduction in the overall NAFLD activity score by saroglitazar (3 mg/kg) was significantly more prominent than pioglitazone (25 mg/kg) and fenofibrate (100 mg/kg). Pioglitazone and fenofibrate did not show any improvement in steatosis, but partially improved inflammation and liver function. Antifibrotic effect of saroglitazar (4 mg/kg) was also observed in carbon tetrachloride-induced fibrosis model.. Saroglitazar, a dual PPARα/γ agonist with predominant PPARα activity, shows an overall improvement in NASH. The effects of saroglitazar appear better than pure PPARα agonist, fenofibrate and PPARγ agonist pioglitazone.

Topics: Alanine Transaminase; Animals; Aspartate Aminotransferases; Biomarkers; Diet, High-Fat; Fenofibrate; Hep G2 Cells; Humans; Kupffer Cells; Liver; Male; Mice; Mice, Inbred C57BL; Non-alcoholic Fatty Liver Disease; Phenylpropionates; Pioglitazone; PPAR alpha; Pyrroles; Tumor Necrosis Factor-alpha